Antipsychotic Synthesis Lab Report

Photolytic Degradation of Flupentixol-Melitracen

Chapter One
Introduction

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1. ANTIPSYCHOTIC
1.1 Antipsychotic
An antipsychotic also known as neuroleptic is a tranquilizing psychiatric medication which is used to treat psychosis, schizophrenia and bipolar disorder. Now it is increasingly being used to treat the non-psychotic disorders. Psychosis disorder included delusions or hallucinations.
Delusion is the pathological condition that is the result of an illness or progressing of illness. A first generation of antipsychotics was discovered in the 1950s which is known as typical antipsychotics. Atypical antipsychotics have been developed as a second generation drug
recently.
Clozapine was the first atypical antipsychotic drug which was developed in 1950s.
Clinically it was introduced in the 1970s. Both generations of the drug have the ability to block the dopamine receptor present in the brain.
1.2 History
Chlorpromazine was the first antipsychotic drug developed as a surgical anesthetic. It was proved that the chlorpromazine is a more effective and specific than lobotomy (At that time lobotomy was used to treat psychosis and also used to reduce behavior and all types of mental functioning). But chlorpromazine caused severe sedation.
In 1952, Henri Laborit described chlorpromazine only as inducing indifference towards what was happening around them in nonpsychotic, nonmanic patients, and Jean Delay and Pierre
Deniker described it as controlling manic or psychotic agitation. The former claimed to have discovered a treatment for agitation in anyone, and the latter team claimed to have discovered a treatment for psychotic illness.
The term neuroleptic was widely used in the late 1950s which is followed by major tranquilizer and later ataraxic. The term tranquilizer was first used by Frederik F. Yonkman in 1953 to differentiate reserpine from the older sedatives.
Antipsychotics are classified into two groups. One is the typical also known as first-generation antipsychotics and the other is atypical also known as second-generation antipsychotics. The typical antipsychotics and the atypical antipsychotics are classified according to their chemical structure and their pharmacological properties respectively.
1.3 Side effects
Antipsychotics have several side effects. These are included:
 Second generation antipsychotics (atypical) causes diabetes mellitus and fatal diabetic ketoacidosis.  Using antipsychotic drugs may cause pancreatitis.

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 Olanzapine and clozapine (atypical antipsychotic) are responsible for well-documented metabolic side effects that is associated with diabetic can be life- threatening.
 The risk of fatal heart attack is increased using antipsychotics.
 The number of white blood cells is potentially reduced by clozapine. This condition is known as agranulocytosis.
 Tardive dyskinesia is one of the major side effects of antipsychotics.
 Other serious side effects are tardive dyskinesia, dysphoria, idiopathic Parkinsonism, sexual dysfunction, dystonia, hyperprolactinaemia.
 A minor loss of brain tissue was reported in schizophrenic’s patients when treated with antipsychotics in Feb. 2011.
1.4 Mechanism of action
All antipsychotic drugs gives psychotic effect by blocking D2 receptors (Dopamine receptors) that is present in the brain cells. Excess amount of dopamine is released through mesolimbic pathway that has been linked to psychotic experiences. Blocking the dopamine receptor by this pathway is thought to control psychotic experiences. Typical antipsychotics also block the dopamine receptors through several pathways like nigrostriatal pathway, mesocortical pathway, and tuberoinfundibular pathway.
Atypical antipsychotic drugs also block the dopamine receptor (D2 receptors). Some atypical antipsychotic drugs also block the 5HT2A, C and 5HT1A receptors which are known as serotonin receptor. By blocking the serotonin receptor helps to prevent the negative symptoms of schizophrenia. 1.5 Fluxit
Fluxit® is the Brand name of Opsonin Pharma Limited. It is an antipsychotic drug. It contains 500 mcg as Flupentixol Dihydrochloride BP and Melitracin 10 mg as melitracen hydrochloride INN.
Flupentixol is a neuroleptic with anxiolytic and antidepressants properties of its own when given in small doses, and Melitracen is a bipolar thymoleptic with activating properties in low doses.
The combination preparation gives antidepressant, anxiolytic, and activating properties.
The color of the tablet is blue. It is a round shape and film-coated tablet. Each carton contains
10x5 tablets in blister pack.

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1.6 Flupentixol dihydrochloride
Flupentixol dihydrochloride is white or almost white powder and chemically it is known as
2-[4-[3-[(EZ)-2-(trifluoromethyl)-9H-thioxanthen-9-ylidene]
propyl] piperazin-1-yl] ethanoldihydrochloride. Its molecular formula C23H25F3N2OS, 2HCl and molecular weight is
507.44. Though, it is soluble in water and alcohol but practically insoluble in methylene chloride.

Figure 1.1: Molecular Structure of flupentixol hydrochloride
1.7 Melitracen hydrochloride
Melitracen hydrochloride is an amorphous in nature and off white powder. The chemical formula of melitracen hydrochloride is 3-[10, 10-Dimethyl-9(10H)-anthrylidene]-N, Ndimethylpropylamine hydrochloride. It’s molecular formula C21H25N.HCl and molecular weight is 327.90.

Figure 1.2: Molecular Structure of Melitracen hydrochloride
Flupentixol hydrochloride gives anxiolytic effect by blocking D2 receptors (Dopamine receptors) that is present in the brain cells. Flupentixol blocks D2 receptors and ultimately inhibit psychotic illness. Melitracin hydrochloride is a tricyclic antidepressant inhibits norepinephrine and serotonin reuptake. The combination of flupentixol and melitracen is useful for the treatment of trigeminal neuralgia.

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1.8 Pharmacokinetics
Maximal serum concentration is reached in about 4 hours after oral administration of flupentixol and about 4 hours after oral administration of melitracen. The biological half-life of flupentixol is about 35 hours and that of melitracen is about 19 hours. The combination of flupentixol and melitracen does not seem to influence the pharmacokinetic properties of the individual compounds.
1.9 Indication & Dosage
Adult: Per tablet contains flupentixol 0.5 mg and melitracen 10 mg: 1 tablet in the morning and at midday. Sometimes double morning dose in severe cases. Not to exceed 4 tablets daily.
Elderly: Per tablet contains flupentixol 0.5 mg and melitracen 10 mg: 1 tablet in the morning. For severe cases: 1 tablet in the morning and at midday.
1.10 Contraindications
Circulatory collapse, depressed level of consciousness due to any cause, coma, severe depressing requiring hospitalization or electroconvulsive therapy. Not recommended for use in states of excitement or over activity.
1.11 Adverse Drug Reactions
Drowsiness, dry mouth, constipation, vomiting, dyspepsia, diarrhoea, abdominal pain, nausea, flatulence. Extrapyramidal effects, especially in the initial phase of the treatment.
Tachycardia, palpitations, prolonged QT interval, hypotension. Thrombocytopenia, neutropenia, leukopenia, agranulocytosis. Dyspnoea, myalgia, muscle rigidity, micturition disorder, urinary retention. Increased appetite and wt. abnormal glucose tolerance and LFTs. Insomnia, depression, nervousness, agitation, libido decreased.
1.12 Drug Interactions
Increased risk of adverse effects when used with alcohol. May potentiate the effects of general anesthetics and anticoagulants, and prolong the action of neuromuscular blockers. May increase anticholinergic effects of atropine and drugs with anticholinergic activity. May increase risk of neurotoxicity when used with sibutramine or lithium. Avoid concurrent usage with drugs that cause QT prolongation or cardiac arrhythmias. May inhibit metabolism of TCAs. May antagonize effects of adrenaline and sympathomimetic, and reverse antihypertensive effects of guanethidine. Photolytic Degradation of Flupentixol-Melitracen

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1.13 Overall objectives of the research
The objective of this experiment is to determine the effect of flupentixol-melitracen combination products in various conditions (control, sunlight, normal light, 25watt and 40watt light condition).
My research work was the determination of photolytic degradation of flupentixol-melitracen combination products. The objective of my experiment was to determine the effect of flupentixol-melitracen combination products in various conditions (control, sunlight, normal light, 25watt and 40watt light condition).To fulfill my project I choose Fluxit ® which contains flupentixol-melitracen combination tablet.

Photolytic Degradation of Flupentixol-Melitracen

Chapter Two
Literature Review

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LITERATURE REVIEW
Einosuke et al. (Einosuke et al., 1997) have developed a method high-performance liquid chromatographic method for the forensic analysis of amitriptyline, amoxapine, clomipramine, desipramine, dosulepine, doxepin, imipramine, maprotiline, melitracen, mianserine and nortriptyline. They used two different C8 reversed-phase columns (column 1: 100 mm × 4.6 mm
I.D., particle size 2 μm, TSK gel Super-Octyl; column 2: 100 mm × 4.6 mm I.D., particle size 5 μm, Hypersil MOS-C8) for the separation process. The mobile phase and the flow rate were methanol-20 mM KH2PO4 (pH 7) (60:40, v/v) and .6 ml/min for both columns, respectively.
The absorbance was monitored at 254 nm. During determination of these drugs, they found 2 μm particles give five times greater sensitivity than with the 5 μm particles. Column 1 retention times were shorter than column 2. The new ODS column packing with 2 μm particle sizes gives higher sensitivity and a shorter analysis than conventional ODS column packing that is applied to the analysis of biological samples.
Silke et al. (Silke et al., 1999) developed a high-performance liquid chromatography (HPLC) method for quantification of both isomers of the thioxanthene neuroleptic flupentixol and of the butyrophenone derivative haloperidol in human serum. An extraction process was performed with diethyl ether–n-heptane (50:50, v/v). They used Hypersil cyan propyl silica column
(250×4.6 mm, 5 μm particle size) in an isocratic normal-phase HPLC system. The ultraviolet detection was monitored at 254 nm. The limit of quantitation for flupentixol was 0.5 ng/ml. It was found that the flupentixol is sufficient to quantify in serum after administration of clinically adjusted doses.
According to the McClean et al. (McClean et al., 2000) Electrospray ionization quadrupole iontrap mass spectrometric (ESI-MS) characterization of the anti-psychotic drugs is presented and possible mechanisms for the observed MSn fragmentation patterns proposed. Their detection and determination in the hair of a patient under clinical treatment for schizophrenia was done by a validated liquid chromatography (LC)-MS-MS method. Some are identified and determined in this hair sample.
Wolfgang et al. (Wolfgang et al., 2001) analyzed hair samples of psychiatric patients using liquid chromatography–tandem mass spectrometry (LC–MS–MS) for neuroleptics. These neuroleptics are flupentixol, zuclopenthixol, thioridazine, haloperidol, clozapine, and penfluridol. They administered these neuroleptics to the patients regularly for a minimum of six months for their study purpose. Sample preparation was performed by washing, powdering with a ball mill, and extraction of drugs from hair by ultra-sonication with methanol, cleanup by solid-phase extraction and subsequent LC–MS–MS analysis using multiple reactions monitoring (MRM).
The range of calibration was 0.05 to 10 ng/mg for all drugs. They used 20-50 mg of hair powder and the detection limits of LC–MS–MS were found below0.05 ng/mg for all drugs tested.
Flupentixol (5 mg/day; light brown hair) was not detected by these methods.

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Garay Garcia et al. (Garay Garcia et al., 2003) have developed a specific reversed phase-high pressure liquid chromatography (RP-HPLC) method for the simultaneous determination of clozapine (CZP), loxapine (LXP), zuclopenthixol (ZPT) and flupenthixol (FPT) in plasma. These drugs are frequently used for the treatment of schizophrenia and other neuropsychiatric diseases.
Carpipramine, a dihydrodibenzazepine was an internal standard (I.S.). The drugs were extracted from human plasma by using liquid-liquid procedure. They used XTerra MS C18 column for analysis. The linearity range was 50-1000 microg/l. The limit of quantification (LOQ) was 15 microg/l for clozapine and loxapine and 20 microg/l for zuclopenthixol and flupenthixol. The correlation coefficient value was 7.2% or less with accuracies within 10% for the three concentrations. It is an isocratic and rapid method (run time0.998 for both analysts. The range of 60.9–75.1% was found for the recovery of flupentixol, melitracen and internal standard. They were found the lower limit of detection quantitation is to 26.1 pg/ml for flupentixol and 0.206 ng/ml for melitracen. The accuracy level for flupentixol was 97.6–
103.0% and for melitracin was 98.7–101.7% by using Intra- and inter-day precision of the assay.
Bench-top, auto sampler and long-term storage stability as well as freeze/thaw cycles were found to be a suitable bioequivalence study of flupentixol and melitracen in healthy human male volunteers. Roman et al. (Roman et al., 2007) study on Antipsychotic drugs that are mainly involved in intoxications and suicides. Nowadays seven low-dose new drugs named buspirone; fluphenazine, flupenthixol, perphenazine, risperidone, ziprasidone, and zuclopenthixol are available in market.
They have put further demands on assays used with the aim of developing a validated liquid chromatography-tandem mass spectrometry assay for the quantitation of these drugs in human postmortem blood. Compounds were separated on a Zorbax SB-CN column after liquid-liquid

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extraction using methyl t-butyl ether. For all drugs calibration curves were linear in the range
0.8–100 μg/L (r > 0.998) having both within- and between-day coefficients of variation lower than 25% for all drugs at the LOQ, and extraction recoveries ranged between 58 and 112%. Only a few intoxications were identified from 54 authentic samples. So, antipsychotic drugs must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases.
Sarah Wille (Ghent, 2008) given an overview of the development of a gas chromatographic mass spectrometric (GC-MS) method for new generation antidepressants (ADs) and their metabolites.
His first chapter gives me an overview of the ADs and the relevance of monitoring those compounds in clinical and forensic settings are given in chapter I, and chapter II gives an overview of the objectives of the research.
The solid phase extraction development for different biological matrices such as plasma, blood, brain and hair tissue were described in chapter III. GC-MS was described in chapter IV that was applied, and the derivatization of the extracts was evaluated and optimized. After the sample preparation, He used gas chromatography mass spectrometry for the separation and detection of
ADs and metabolites. Electron ionization, positive and negative ion chemical ionization is described in chapter V. The validation procedure is described in chapter VI. Chapter VII and
VIII describes the he applicability of the developed and validated method for evaluation such as the usefulness of the developed method in a clinical setting and application of the procedure to post-mortem cases with matrices (whole blood, brain tissue and hair), respectively.
Xiao-Cong et al. (Xiao-Cong et al., 2009) extracted Flupentixol and an internal standard, loperamidefrom plasma by a convenient liquid-liquid extraction process. For the chromatographic separation they used Thermo Hypersil-Hypurity C18 column and the mobile phase was 10 mM ammonium acetate–acetonitrile–methanol (26:62:12, v/v/v). A quadrupole mass spectrometer was used for the quantification of protonated analyte in a positive-ion mode.
The concentration range was 0.039–2.5 ng mL−1. Intra-day and inter-day precision (RSD %) were less than 13.05%. It was successfully applied for the determination of pharmacokinetics of flupentixol in human plasma.
Bermudez-Saldana et al. developed a Micellar liquid chromatography methods for quality control of pharmaceutical preparations (capsules, pills, tablets, injections) containing the tricyclic antidepressants amineptine, amitriptiline, clomipramine, doxepin, imipramine, melitracen and nortriptyline alone or together with other CNS drugs like diazepam, medazepam and perphenazine. They used cetyltrimethylammonium bromide as mobile phases. The UV detection was rapid and reproducible. Micellar liquid chromatography is better for determination of highly hydrophobic compounds such as TCAs in a short time using mobile phases containing low organic solvent concentrations and usual flow rates than RP-HPLC methods. Before injecting into the chromatographic system, samples preparation only requires solution and adequate dilution with the mobile phase.

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Sheikh et al. (Sheikh et al., 2009) have developed a simple, selective, rapid, precise and economical reverse phase HPLC method for estimation of Flupenthixol Hydrochloride in pharmaceutical dosage forms. They used Eurospher C18 (250 cm×4 mm) column with precolumn and the mobile phase was Acetonitrile: Water (pH 3.0) (50:50 v/v). The flow rate was
1 ml/min. Absorbance was occurred at 229nm. The retention time for flupenthixol HCl was 3.98.
This method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantization and solution stability.
Sharma et al. (Sharma et al., 2010) were employed a method for solubilization of poorly water soluble drugs for spectrophotometric estimations using various organic solvents like methanol, chloroform, alcohol, dimethyl formamide, acetonitrile, hexane, acetone and carbon tetrachloride.
But they were faced some limitations include higher cost, toxicity and error in analysis due to volatility. So, they developed three new spectrophotometric methods for minimizing the limitations. These methods are simple, accurate, environmental friendly, cost effective, safe, and sensitive. There primary object was to employ these hydrotropic solutions using costlier organic solvents for extracting the extract the drugs from their dosage forms. They have developed
Ultraviolet absorption spectrophotometric method for the estimation of poorly water soluble drugs like Melitracen HCl in pharmaceutical formulations. The maximum selectivity for
Melitracen HCl was 286.5 nm respectively. But the hydrotropic solutions did not show any absorbance above 306 nm; as a result, interference in the estimation was not seen. Thus the results have been validated and recovery statistically.
According to the Sheikh et al. (Sheikh et al., 2010) a new, simple, sensitive and specific spectrophotometric analytical method was developed and validated for quantization of
Flupenthixol and Melitracen combination dosage form based on the simultaneous estimation of drugs in a binary mixture without previous separation by absorbance at 283.60 nm and 229.40nm by Imran A Sheikh et al. The average percent recovery was found to be 99.98+0.43and
99.91+0.10. The result of the method lies within the prescribe limit of 98-102% shows that method is free form interference from excipients.
M. Aubert et al. (M. Aubert et al., 2010) used Ultra high performance liquid-chromatography linked to mass spectrometry for determination of photo degradation of the flupentixol structure after irradiation at 254 nm of aqueous solution of flupentixol. The fragmented parent ions allowed to accurate mass measurements of both parent and daughter ions that were established on a hybrid linear ion trap–orbit rap mass spectrometer. It also allowed proposing plausible structures for the main photolysis products of flupentixol. The main photoproduct from the total of nine photoproducts is generated following the addition of a hydroxyl group on the double bond adjacent to the thioxanthene ring. Secondary photoproducts were also observed.
Huang et al. (Huang et al., 2010) provided constructive suggestions for the production and quality inspection of drugs. At first they collected quality inspection data of 198 batches of

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flupentixol and melitracen tablets by Laboratory Information Management System (LIMS) in
Guangdong institute. They showed that the maximum impact on the quality items content uniformity of tablets. Laboratory Information Management System is highly responsible collecting large quantities of drug data, and the quality index serves as an effective means for the evaluation of drug quality.
Sasmita et al. (Sasmita et al., 2010) have developed a simple, precise and economical spectrophotometric method for the simultaneous estimation of Flupentixol+Melitracen combination (tablet) dosage form. The first method is developed on the use of simultaneous equation, the second method is developed on the simultaneous equation using AUC of the two drugs, the third method is developed on the use of absorbance ratio method and the fourth one is based on first order derivative method. Both drugs follow the Beer’s law. The International
Conference on Harmonization suggested following the analytical performance parameters for validating the method. All validation parameters must be within the acceptable range.
Mr. B. Lakshminarayana (Mr. B. Lakshminarayana Pharm 2011) has developed five sensitive, simple and specific methods for the quantitative estimation of Flupentixol dihydrochloride in bulk and pharmaceutical formulations. Five methods are Zero, First; second order derivative
Spectroscopy, RP-HPLC and HPTLC.
In case of Zero order derivative Spectroscopy, Mr. B. Lakshminarayana prepared a stock solution by weighing 100 mg of Standard Flupentixol dihydrochloride in 100 ml volumetric flask with dH2O. He also prepared final stock solution to produce 100 mcg / ml with dH2O.He also prepared further dilutions as per procedure. The maximum absorbance was found at 229nm for the drug solution, and the linearity was of 3-15 mcg / ml (concentration range). 0.9999 was found as a Correlation coefficient. He found regression equation that is Y = 0.0612 C + 0.0046.
It was a validated method for linearity, accuracy, precision, limit of detection, limit of quantitation and ruggedness. He was found the limit of detection and limit of quantitation is to be
0.128 (mcg / ml) and (0.390 mcg / ml), respectively for the estimation of Flupentixol dihydrochloride. The range of 98.63-99.87% was found as a recovery of Flupentixol dihydrochloride. In case of First order derivative Spectroscopy, Mr. B. Lakshminarayana prepared a stock solution by weighing 100 mg of Standard Flupentixol dihydrochloride in 100 ml volumetric flask with dH2O. He also prepared final stock solution to produce 100 mcg / ml with dH2O.He also prepared further dilutions as per procedure. The maximum absorbance was found at 222nm for the drug solution, and the linearity was of 3-15 mcg / ml (concentration range). 0.9996 was found as a Correlation coefficient. He found regression equation that is Y = 0.0158 C + 0.0015.
It was a validated method for linearity, accuracy, precision, limit of detection, limit of quantitation and ruggedness. He was found the limit of detection and limit of quantitation is to be
0.12 (mcg / ml) and (0.37 mcg / ml), respectively for the estimation of Flupentixol

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dihydrochloride. The % RSD values were less than 2. The range of 99.21-100.87% was found as a recovery of Flupentixol dihydrochloride.
In case of Second order derivative Spectroscopy, Mr. B. Lakshminarayana prepared a stock solution by weighing 100 mg of Standard Flupentixol dihydrochloride in 100 ml volumetric flask with dH2O. He also prepared final stock solution to produce 100 mcg / ml with dH2O.He also prepared further dilutions as per procedure. The maximum absorbance was found at 214nm for the drug solution, and the linearity was of 3-15 mcg / ml (concentration range). 0.9998 was found as a Correlation coefficient. He found regression equation that is Y = 0.036 C + 0.0001. It was a validated method for linearity, accuracy, precision, limit of detection, limit of quantitation and ruggedness. He was found the limit of detection and limit of quantitation is to be 0.36 (mcg / ml) and (1.11 mcg / ml), respectively for the estimation of Flupentixol dihydrochloride. The range of 99.18-99.87% was found as a recovery of Flupentixol dihydrochloride.
In case of High Performance Liquid Chromatography method, Mr. B. Lakshminarayana used
Gemini C-18 (250x4.6mm, 5 µm) as a stationary phase with in an isocratic condition and the mobile phase was Methanol: Water (65: 35, v/v). The flow rate was 1.0mL/min and at 229 nm.
The effluent was monitored. The retention times of Flupentixol dihydrochloride was 4.28min. . It was a validated method for linearity, accuracy, precision, limit of detection, limit of quantitation and ruggedness. He was found the limit of detection and limit of quantitation is to be 0.11 (mcg / ml) and 0.11(mcg / ml), respectively for the estimation of Flupentixol dihydrochloride. The range of 98.95-99.88% was found as a recovery of Flupentixol dihydrochloride.
In case of High Performance Thin Layer Chromatography method, Mr. B. Lakshminarayana used aluminium plates coated with silica gel 60 F264 as stationary phase and the mobile phase was toluene: glacial Acetic Acid (7: 3, v/v). At 229 nm the densitometry evaluation of separated bands was performed. The Rf value was 0.21 +/- 0.02. The validated calibration range was 3001500 ng per spot (r2 =0.9993). He was found the limit of detection and limit of quantitation is to be 6.24 ng per spot and 18.92 ng per spot, respectively for the estimation of Flupentixol dihydrochloride. It was a validated method for linearity, accuracy, precision, limit of detection, limit of quantitation and ruggedness according to the ICH guidelines.
Akhil et al. has been described a simple, precise and accurate method for the estimation of
Flupenthixol and Melitracen in formulation. They were used SP Thermo Separation Products
HPLC system and Thermo scientific BDS C8 column (150×4.6 mm) in isocratic mode that is composed of LC-10AT pumps and UV detector and the mobile phase was potassium dihydrogen phosphate buffer: methanol: ACN, (3:6:1). The flow rate was 1.5 ml/min and the effluent was monitored at 230nm. The retention times of Melitracen and Flupenthixol were 3.16 and 5.31 min respectively. The linearity range for Melitracen and Flupenthixol were 80- 120 µg/ml. The
%RSD values of precision were less than 2 is useful for the good reproducibility method. The method validation parameters were found to be within the USP standards. These are theoretical

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plates, resolution, tailing factor, LOD and LOQ. The excipients consisting in the formulation were not interfered the method. As a result method is become suitable for routine analysis, combined formulations of Melitracen and Flupenthixol.
Chhalotiya et al. (Chhalotiya et al., 2011) were developed a reversed-phase high-performance liquid chromatographic method for determination of melitracen hydrochloride and flupentixol dihydrochloride in tablet dosage form. It was very specific and simple method. They used a
Brownlee C-18 column as stationary phase. For 5 μm particle size they used column having 250
× 4.6mm i.d. in isocratic mode and the mobile phase was 0.025M potassium dihydrogen phosphate: methanol (10: 90, v/v; pH 7.3). The flow rate was 1.0mL/min and at 230 nm. The effluents were monitored. The retention time of melitracen hydrochloride was 7.75min and flupentixol dihydrochloride was 5.50min. The range of linearity for melitracen hydrochloride and flupentixol dihydrochloride was 0.5–60 μg/mL. 99.81–100.77% and 99.42–100.12% were obtained as a recovery for melitracen hydrochloride and flupenthixol dihydrochloride, respectively. It was successful and validated method.
Mohd et al. (Mohd et al., 2011) used a simple and cost effective spectrophotometric method for the determination of flupenthixol dihydrochloride in pure form and in pharmaceutical formulations. Flupenthixol dihydrochloride was highly soluble in methanol that ensured adequate drug solubility and maximum assay sensitivity. At 230 nm, the linearity range for flupenthixol dihydrochloride was obtained as 1-15 μg/ml that gives a linear regression equation,
Y = 0.0639X + 0.0013, where Y is the absorbance and X is the concentration (in μg/ml) of pure drug solution. The correlation coefficient value was 0.9997. The detection limit was 0.324 μg/ml and the quantification limit was 0.982 μg/ml. It was a successful method for the determination of flupenthixol dihydrochloride in pharmaceutical formulations without any interference from common excipients.
Ahmed A. Elbary et al. (Ahmed A. Elbary et al., 2011) used Eudragit E100 as a taste masking to prepare bitterless rapid disintegrating tablet. For preparation the tablet they used 2% sodium starch glycolate, 3% crosscarmellose sodium and 4% crosprovidone. They used mass extrusion technique for preparation of these tablets. The blend was examined for angle of repose, bulk density, tapped density, compressibility index and Hausner’s ratio. Hardness, drug content, friability, disintegration time in vitro and in vivo, wetting time and dissolution time of compressed tablets were evaluated. X-ray diffraction and Fourier transform infrared spectroscopy were used for preparing the tablet. There were nine formulas showed in-vitro disintegration times and ten formulas showed in-vivo disintegration times. In vitro test showed that the release pattern of the superdisintigrants follow the descending order like crosprovidone > crosscarmellose sodium > sodium starch glycolate. Maximum in-vitro dissolution rate was found in F10 formulation, so f10 was considered the best formulations than others. Crosprovidone is suitable for preparing rapid disintegrating the Flupentixol Dihydrochloride tablet that is found in
F10 formulation.

Photolytic Degradation of Flupentixol-Melitracen

Chapter Three
Materials & Testing
Procedure

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3.1 MATERIALS
3.1.1 Sample Collection
500 tablets of Flupentixol-melitracen a combined drug (Fluxit, manufactured by Opsonin
Pharma) of same batch, were collected from the local pharmacy shop in Dhaka as a sample
Table 3.1.1: Samples used in the experiment including source
Materials Name

Source (Supplier Name)

Fluxit tablets

Opsonin Pharma ltd.

Table 3.1.2: Reagents used in the experiment including source
Reagents Name
Distilled Water
Concentrated Sulfuric acid

Source (Supplier Name)
Laboratory(East West University)
Germany

Table 3.1.3: Equipment used in the experiment including source
Serial no.

Equipment

Source (Supplier Name)

1

Vernier Caliper

China Supplier

Shanghai, China

2

Spectrophotometer

Shimadzu UV-1800

Japan

3

Distill Water Plant

SMIC

China

4

Electronic Balance

Precisa XB120A

Switzerland

5

Friability tester

Veegoindia

India

6

Hardness tester

Manually operated hardness tester

India

Photolytic Degradation of Flupentixol-Melitracen

Figure: 3.1.1 [Left to right] Vernier Caliper, Shimadzu UV-1800 Double Beam
Spectrophotometer, Distilled water Plant

Figure: 3.1.2 [Left to right] Hardness Tester, Electronic Balance, Friability tester

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Table 3.1.4: List of Apparatus used in this project
Serial no.

Apparatus

1

Forceps

2

Funnel

3

Beakers

4

Spatula

5

Glass Rod

6

Filter Papers

7

Aluminum foil paper

8

Transparent plastic paper

9

Plastic Containers

10

Mortar & Pastels

11

Test tubes

12

Volumetric Flasks (50 ml & 100 ml)

13

Pipette pumper

14

Pipette

15

Volumetric Pipette

3.2 Testing procedure
3.2.1 Standard curve and equation derivation
The standard curve was prepared to compare the test result. For the preparation of standard curve the average weight of 5 tablets were taken and was crashed by using mortar and pestle.
The powder drugs to dissolve in 100ml of 0.1N H2SO4 solvent after measuring the powder drugs using a balance.
Series dilution was carried out with the standard stock solution by pipetting 2 ml of the stock solution in test tube (1) and adding 8 ml of solvent to it. Then again pipetting 2 ml solution from test tube (1) to test tube (2) and adding 8 ml solvent to it. This was continued for more 3 times. It is called a known concentration of Flupentixol dihydrochloride.

Photolytic Degradation of Flupentixol-Melitracen

20

Table 3.2.1: Concentration of Flupentixol dihydrochloride
Serial no.
Concentration (mg/ml)
1
0.01
2
0.002
3
0.0004
4
0.00008
5
0.000016
That was also followed in concentration of Melitracen hydrochloride
Table 3.2.2: Concentration of Melitracen hydrochloride
Serial no.
1
2
3
4
5

Concentration (mg/ml)
0.2
0.04
0.008
0.0016
0.00032

Using UV-Spectrophotometer absorbance was taken above all the solution for flupentixol dihydrochloride (at 229 nm wavelength) and for melitracen hydrochloride (at 258 nm wavelength). The observed value was plotted against concentration and a linear regression equation was obtained.
3.2.2 Sample collection
To determine the photo stability of the drug the tablets were subjected to various types of photo exposure, which are:


Electric Bulb exposure (25 watt, 40 watt)



Sunlight exposure(summer)



Exposure to normal room temperature (14 days, 28 days, 42 days)

3.2.2.1 Electric Bulb exposure (25 watt, 40 watt)
Two power ranges of bulb, 25 watt and 40 watt were used as the artificial light source.
Thirty tablets were kept on a solid surface and were placed under 25 watt containing lamp. A thermometer was kept behind the tablets submerge in a glass of water to measure the temperature. We kept the tablets for nine hour and after each three hour 10 tablet were collected.
In three hour 10 tablets where collected as 3 hour exposed sample and with more 3 hour the
6 hour exposed sample and finally with addition of more 3 hour the 9 hour sample was collected.

Photolytic Degradation of Flupentixol-Melitracen

21

After the sample collection analysis of the sample was conducted by measuring some physical parameters and UV visible spectroscopy to determine the potency of the drug.
3.2.2.2 Sunlight exposure
For Sunlight exposed sample the tablets were exposed to the summer sun. Thirty tablets were kept on a paper with a thermometer for the sun exposure. In three hour 10 tablets where collected as 3 hour exposed sample and with more 3 hour the 6 hour exposed sample and finally with addition of more 3 hour the 9 hour sample was collected. Each sample containing 10 tablets.
3.2.2.3 Exposure to normal room temperature
The exposure of the tablets was done in normal room temperature. Hundred tablets were kept in the normal room temperature in a plastic transparent container. We rapped the container
Photolytic Degradation of Flupentixol-Melitracen 24 with transparent plastic paper so that moisture and air cannot enter to the container. We started the preservation of the tablets in the box on 23rd February 2012. We fixed our observation date after 14 days, 28 days, 42 days and each time we took out 10 tablets from the container. After the sample collection analysis of the sample was conducted by measuring some physical parameters and UV visible spectroscopy to determine the potency of the drug.
3.2.2.4 Sample analysis
After the collection of the sample it was time to proceed to the analysis step. At first the average weight of the three sample tablets were taken by the electronic balance. Then the tablets were crashed to fine powder by the help of mortar and pestle. The average weight that was previously accounted was then weighted from the crashed powdered sample and was allowed to dissolve into 100ml of 0.1N H2SO4 in a 100 ml volumetric flask. The solution of the volumetric flask was then filtered thought a filter paper.10 ml of the filtrate was pipetted to a 100ml volumetric flask and 0.1 N H2SO4 was then added to the filtrate. After all that, the sample solution was prepared for the potency test using UV-Spectroscopy. For that, each of the tests was run against a blank, and for the test the test solution was poured into the quartz cell. The quartz cell was then placed into the holder situated inside the machine. Using a specified software technology the absorbance of the sample solution was established in the computer.
3.2.3 Physical parameters determination
3.2.3.1 Color Test
We observed the color of tablets to find any change in color. We used a digital camera to take the picture of the tablets for the comparative observation. In case of taking picture we did not use flash. We maintain a fixed camera with fixed resolution.

Photolytic Degradation of Flupentixol-Melitracen

22

3.2.3.2 Weight Variation Test
Weight variation test is most significant because it has a relationship with content uniformity of a solid dosage forms. Any of the following factors, can produce excessive tablet variations: 1. Poor granulation flow properties, resulting in uneven die fill.
2. A wide variation in granulation particle size, which result in a variation in die fill density as a function of particle size and particle size distribution at different points in the production run. 3.2.3.2.1 Procedure
1. 10 tablets were taken and weighed all the tablets
2. The average was taken and it was considered as the standard weight of an individual tablet 3. All the tablets were weighed individually and observed whether the individual tablets are within the range or not. The variation from the average weight in the weights not more than two tablets must not differ more than the percentage listed below:
Table 3.2.3: Accepted percentage list for the weight variation test of tablets
Weight of tablet
130 mg or less
More than 130 to 324 mg
More than 324 mg

Percentage difference
±10%
±7.5%
±5%

3.2.3.2.2 Calculation
We used following equation to determined % Weight Variation of tablets
% Weight Variation = (A~I/I) ×100. Where, Initial Weight of Tablet, I (gm) Average weight of
Tablet, and A (gm)
3.2.3.3 Thickness test
The thickness test was carried out to measure the thickness of the sample tablet, to determine the deviation of the tablet thickness due to the exposure of the light. It was done by using a Vernier caliper.
3.2.3.3.1 Procedure
1. First placing the tablet between the two jaws of the Vernier caliper.
2. Then, the main scale reading was taken.

Photolytic Degradation of Flupentixol-Melitracen

23

3. The Vernier scale was taken also.
4. The two reading was added together by multiplying with the Vernier constant.
3.2.3.3.2 Calculation
We used following formula to determined thickness of the tablets.
Thickness of the table = reading of cm scale + (reading of Vernier scale x Vernier error)
3.2.3.4 Hardness Test of Tablets
Tablet hardness is usually expressed as the load required crushing a tablet placed on its edge. Hardness is thus sometimes termed the tablet crushing strength. The suitability of a tablet in regard to mechanical stability during packaging and shipment can usually be predicted on the basis of hardness. Tablet hardness, in turn, influences tablet density and porosity. It may affect tablet friability and disintegration time. It usually affects drug dissolution and release and it may affect bioavailability.
3.2.3.4.1 Procedure
1. The slide scale of the hardness tester was made zero
2. One tablet was placed vertically between two jaws.
3. Force was applied with a screw thread and spring until the tablet fractured.
4. Reading in Kg was taken from the sliding scale.
3.2.3.5 Friability Test of Tablets
Friction and shock are the forces that most often cause tablets to chip, cap or break. The friability test is closely related to tablet hardness and is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping. The value is expressed as a percentage. 3.2.3.5.1 Procedure
1. 10 tablets were weighted. It was considered as an initial reading
2. The tablet were placed in the section 1 of the drum of the friability tester and rotated
100 times.
3. The tablets were re-weighted. It was considered as a final reading.
4. The percent loss was calculated.
5. According to the U.S.P the tablets should not lose more than 1% of their total weight
3.2.3.5.2 Calculation
We used following formula to determined Friability of the tablets
% weight loss = (Initial weight – Final weight) ÷Initial weight × 100%

Photolytic Degradation of Flupentixol-Melitracen

Chapter Five
Result & Discussion

24

Photolytic Degradation of Flupentixol-Melitracen

25

4.1 RESULT
4.1.1 Standard curve preparation
Different absorbance was found for different dihydrochloride that were given in the following table.

concentration

of

Flupentixol

Table 4.1: Concentration and Absorbance for Standard Curve of Flupentixol dihydrochloride
Concentration (mg/ml)

Absorbance

0.01

1.087

0.002

0.221

0.0004

0.03

0.00008

-0.01

0.000016

-0.007

We found a straight line by plotting the concentration against the absorbance of Flupentixol dihydrochloride. From the Standard Curve we derived the equation Y=109.98X-0.0107 and
R2=0.9997. We use this equation to get the concentration from different samples absorbance of
Flupentixol dihydrochloride.

Figure 4.1: Absorbance vs. concentration of Flupentixol dihydrochloride
Different absorbance was found for different concentration of Melitracen hydrochloride that was given in the following table.

Photolytic Degradation of Flupentixol-Melitracen

26

Table 4.2: Concentration and Absorbance for Standard Curve of Melitracen hydrochloride
Concentration (mg/ml)

Absorbance

0.2

0.959

0.04

0.199

0.008

0.036

0.0016

0.002

0.00032

0.015

We found a straight line by plotting the concentration against the absorbance of Flupentixol dihydrochloride. From the Standard Curve we derived the equation Y=4.7824X+0.0032 and
R2=0.9996. We use this equation to get the concentration from different samples absorbance of
Melitracen hydrochloride.

Figure 4.2: Absorbance vs. concentration of Melitracen hydrochloride

Photolytic Degradation of Flupentixol-Melitracen

27

4.1.2 Control Sample
Table 4.1.2.1: Weight variation test of control sample 1
Tablet no.

1
2
3
4
5
6
7
8
9
10

Average initial Final weight, weight, Iav F (gm)
(gm)
0.0964
0.091
0.0909
0.0963
0.09324
0.0918
0.0912
0.0914
0.0948
0.0961
0.0925

Weight variation, % weight F-Iav (gm)
(F~Iav/Iav)*x100
0.00316
-0.00224
-0.00234
0.00306
-0.00144
-0.00204
-0.00184
0.00156
0.00286
0.00074

variation

3.4
2.4
2.5
3.3
1.5
2.2
1.8
1.7
3.1
0.8

Figure 4.1.2.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all

Photolytic Degradation of Flupentixol-Melitracen

28

specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters
Table 4.1.2.2: Thickness test of control sample 1
Tablet no.

Main scale reading(cm), Vernier
M
reading(cm), V

1
2
3
4
5
6
7
8
9
10

0.75
0.75
0.7
0.75
0.8
0.8
0.8
0.8
0.85
0.8

0.0275
0.0275
0.0275
0.0275
0.0275
0.0275
0.0275
0.0275
0.0275
0.0275

scale Thickness of tablets (cm),
(M+V) cm
0.7775
0.7775
0.7275
0.7775
0.8275
0.8275
0.8275
0.8275
0.8775
0.8275

the
i.e.

Figure 4.1.2.2: Thickness of tablets
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.

Photolytic Degradation of Flupentixol-Melitracen

29

Table 4.1.2.3: Hardness test of control sample 1
Tablet no.

Hardness(kg)

Hardness Average (kg)

1

6

6

2

5.5

6

3

6.5

6

Figure 4.1.2.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.2.4: Friability test of control sample 1
Initial weight

Weight after rotation

Weight loss

0.9324

0.932

0.04%

Photolytic Degradation of Flupentixol-Melitracen

30

Figure 4.1.2.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
The graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight
4.1.3 Control sample 2
Table 4.1.3.1: Weight variation test of control sample 2
Tablet no.

Average initial Final weight, Iav (gm)
(gm)

weight,

F Weight
% weight variation variation, F-Iav (F~Iav/Iav)*x100
(gm)
-0.00237
-2.51673

1

0.0918

2

0.094

-0.00017

-0.18052

3

0.0921

-0.00207

0.456621

4

0.0946

0.00043

0.456621

0.093

-0.00117

-1.24243

6

0.0954

0.00123

1.306148

7

0.0943

0.00013

0.138048

8

0.0964

0.00223

2.368058

9

0.0935

-0.00067

-0.71148

10

0.0966

0.00243

2.58044

5

0.09417

Photolytic Degradation of Flupentixol-Melitracen

31

Figure 4.1.3.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit. This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and Xaxis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters

Table 4.1.3.2: Thickness test of control sample 2
Tablet no.

Main scale reading(cm), Vernier
M
reading(cm), V

1

0.6

0.0275

scale Thickness of tablets (cm),
(M+V) cm
0.6275

2

0.6

0.0275

0.6275

3

0.6

0.0275

0.6275

4

0.6

0.0275

0.6275

5

0.6

0.0275

0.6275

6

0.6

0.0275

0.6275

7

0.6

0.0275

0.6275

8

0.6

0.0275

0.6275

9

0.6

0.0275

0.6275

10

0.6

0.0275

0.6275

the
i.e.

Photolytic Degradation of Flupentixol-Melitracen

32

Figure 5.1.3.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.3: Hardness test of control sample 2
Tablet no.
1
2
3

Hardness(kg)
6.2
6.1
6

Hardness Average (kg)
6.1

Figure 4.1.3.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3

Photolytic Degradation of Flupentixol-Melitracen

33

tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.4: Friability test of control sample 2
Initial weight

Weight after rotation

Weight loss

0.9417

0.9414

0.03%

Figure 4.1.3.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight

4.1.3 Potency determination by UV spectroscopy
4.1.3.1 Control sample 1
We found different absorption for different concentration of Flupentixol dihydrochloride and Melitracen hydrochloride on the tablet solution. We got a straight line by plotting the concentration against the absorbance for the Flupentixol dihydrochloride and Melitracen hydrochloride on the tablet solution.
Table 4.1.3.1.1: Concentration and Absorbance of Flupentixol dihydrochloride of Control
Sample-1
Concentration (mg/ml)

Absorbance

0.74

0.802

Photolytic Degradation of Flupentixol-Melitracen

34

Table 4.1.3.1.2: Concentration and Absorbance of Melitracen hydrochloride of Control Sample-1
Concentration (mg/ml)

Absorbance

13.78

0.662

4.1.3.2 Control sample 2
Table 4.1.3.2.1: Concentration and Absorbance of Flupentixol dihydrochloride Control Sample-2
Concentration (mg/ml)

Absorbance

0.699

0.758

Table 4.1.3.2.2: Concentration and Absorbance of Melitracen hydrochloride Control Sample-2
Concentration (mg/ml)

Absorbance

13.6

0.653

4.1.3.3 Electrical Bulb (25 Watt 3 hours)
Table 4.1.3.3.1: Weight variation test of 3 hours sample (Tablet) of 25 watt electrical bulb
Tablet
no.
1

Average
Iav (gm)

weight, Final weight, Weight variation, % weight F (gm)
F~Iav (gm)
(F~Iav/Iav)*x100
0.0935
-0.00042
0.4

2

0.0936

-0.00032

0.3

3

0.0952

0.00128

1.4

4

0.0936

-0.00032

0.3

0.0928

-0.00112

1.2

6

0.0944

0.00048

0.5

7

0.0933

-0.00062

0.7

8

0.0948

0.00088

0.9

9

0.096

0.00208

2.2

10

0.092

-0.00192

2

5

0.09392

variation,

Photolytic Degradation of Flupentixol-Melitracen

35

Figure 4.1.3.3.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit. This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and Xaxis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.
Table: 4.1.3.3.2: Thickness test of 3 hours sample (Tablet) of 25 watt electrical bulb
Tablet
no.
1

Main scale Vernier reading(cm), M reading(cm), V
0.85
0.03

scale Thickness of (cm),i.e.(M+V) cm
0.88

2

0.85

0.03

0.88

3

0.8

0.03

0.83

4

0.9

0.03

0.93

5

0.85

0.03

0.88

6

0.8

0.03

0.83

7

0.9

0.03

0.93

8

0.85

0.03

0.88

9

0.85

0.03

0.88

10

0.85

0.03

0.88

the

tablets

Photolytic Degradation of Flupentixol-Melitracen

36

Figure 5.1.3.3.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.3.3: Hardness test of 3 hours sample (Tablet) of 25 watt electrical bulb
Tablet no.
1
2
3

Hardness(kg)
6
5
5.6

Hardness Average (kg)
5.53
5.53
5.53

6.2
6
5.8
5.6
5.4
5.2
5
4.8
4.6
4.4

Hardness(kg)

Hardness Averege (kg)

1

2

3

4

Figure 4.1.3.3.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3

Photolytic Degradation of Flupentixol-Melitracen

37

tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table: 4.1.3.3.4 Friability test of 3 hours sample (Tablet) of 25 watt electrical bulb

Initial weight
0.9392

Weight after rotation
0.9389

Weight loss
0.03%

Difference of weight in fraibility test
0.929
0.928
0.927

Series1
Initial weight

Weight after rotation Figure 4.1.3.3.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.3.1 Concentration/Potency: 3 hours sample (Tablet) of 25 watt electrical bulb
Table 4.1.3.3.1.1: Concentration of Flupentixol dihydrochloride
Concentration (mg/ml)

Absorbance

0.68

0.737

Table 4.1.3.3.1.2: Concentration of Melitracen hydrochloride
Concentration (mg/ml)

Absorbance

11.9

0.57

Photolytic Degradation of Flupentixol-Melitracen

38

4.1.3.4 Electrical Bulb (25 Watt 6 hours sample)
Table 4.1.3.4.1: Weight variation test of 6 hours sample (Tablet) of 25 watt electrical bulb
Tablet
no.
1
2
3
4
5
6
7
8
9
10

Average initial Final weight, Iav (gm) weight, (gm)
0.0918
0.0907
0.0955
0.0929
0.09281
0.0949
0.0945
0.0902
0.0935
0.0924
0.0917

Weight variation, % weight variation
F F-Iav (gm)
(F~Iav/Iav)*x100
-0.00101
-0.00211
0.00269
0.00009
0.00209
0.00169
-0.00261
0.00069
-0.00041
-0.00111

1.1
2.3
2.9
0.1
2.3
1.8
2.8
0.7
0.4
1.2

Figure 4.1.3.4.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit. This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and Xaxis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.

Photolytic Degradation of Flupentixol-Melitracen

39

Table 4.1.3.4.2: Thickness test of 6 hours sample (Tablet) of 25 watt electrical bulb
Tablet
no.
1

Main scale Vernier reading(cm), M reading(cm), V
0.9
0.03

scale Thickness of the
(cm),i.e.(M+V) cm
0.93

2

0.95

0.03

0.98

3

0.9

0.03

0.93

4

0.95

0.03

0.98

5

0.95

0.03

0.98

6

0.95

0.03

0.98

7

0.95

0.03

0.98

8

0.95

0.03

0.98

9

0.95

0.03

0.98

10

0.95

0.03

tablets

0.98

Figure 4.1.3.4.2: Thickness of tablets
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.

Photolytic Degradation of Flupentixol-Melitracen

40

Table 4.1.3.4.3: Hardness test of 6 hours sample (Tablet) of 25 watt electrical bulb
Hardness(kg)

Hardness Average (kg)

Tablet no.
1

6.8

5.67

2

5.2

5.67

3

5

5.67

Figure 4.1.3.4.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.4.4: Friability test of 6 hours sample (Tablet) of 25 watt electrical bulb
Initial weight

Weight after rotation

Weight loss

0.9281

0.9275

0.07%

Photolytic Degradation of Flupentixol-Melitracen

41

Figure: 4.1.3.4.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.5 Concentration/Potency: 6 hours sample (Tablet) of 25 watt electrical bulb
Table 4.1.3.5.1: Concentration and Absorbance of Flupentixol dihydrochloride

Concentration (mg/ml)

Absorbance

0.477

0.514

Table4.1.3.5.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)

Absorbance

7.3

0.354

Photolytic Degradation of Flupentixol-Melitracen

42

4.1.3.6 Electrical Bulb (25 Watt 9 hours sample)
Table 4.1.3.6.1: Weight variation test of 9 hours sample (Tablet) of 25 watt electrical bulb
Tablet
no.
1
2
3
4
5
6
7
8
9
10

Average initial Final weight, Iav (gm) weight, (gm)
0.091
0.0939
0.0922
0.0917
0.09331
0.0956
0.0976
0.0913
0.0928
0.0926
0.0942

Weight variation, % weight variation
F F-Iav (gm)
(F~Iav/Iav)*x100
-0.00231
0.00059
-0.00111
-0.00161
0.00229
0.00429
-0.00201
-0.00051
-0.00071
0.00089

2.5
0.6
1.2
1.7
2.5
4.6
2.2
0.5
0.8
0.95

Figure 4.1.3.6.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit. This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and Xaxis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters

Photolytic Degradation of Flupentixol-Melitracen

43

Table 4.1.3.6.2: Thickness test of 9 hours sample (Tablet) of 25 watt electrical bulb
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),i.e.(M+V) cm
1
0.85
0.03
0.88
2
0.85
0.03
0.88
3
0.85
0.03
0.88
4
0.9
0.03
0.88
5
0.9
0.03
0.88
6
0.9
0.03
0.88
7
0.85
0.03
0.88
8
0.85
0.03
0.88
9
0.85
0.03
0.88
10
0.85
0.03
0.88

Thicness of the tablets

Thickness of the tablets
(cm),i.e.(M+V) cm
1
0.8
0.6
Thickness of the tablets (cm),i.e.(M+V) cm

0.4
0.2

0
1 2 3 4 5 6 7 8 9 10 11
Number of tablets

Figure 4.1.3.6.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.6.3: Hardness test of 9 hours sample (Tablet) of 25 watt electrical bulb
Tablet no.
Hardness(kg)
Hardness Average (kg)
1

5.5

5.4

2

5.6

5.4

3

5.1

5.4

Photolytic Degradation of Flupentixol-Melitracen

5.7
5.6
5.5
5.4
5.3
5.2
5.1
5
4.9
4.8

44

Hardness(kg)
Hardness Average (kg)

1

2

3

4

Figure 4.1.3.6.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.6.4: Friability test of 9 hours sample (Tablet) of 25 watt electrical bulb
Initial weight
Weight after rotation
Weight loss
0.9331

0.9325

0.06%

Difference of weight in fraibility test 0.929
0.928
0.927

Series1
Initial weight
Weight after rotation Figure 4.1.3.6.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,

Photolytic Degradation of Flupentixol-Melitracen

45

Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
5.1.3.7 Concentration/Potency
Table 4.1.3.7.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.476

0.513

Table 4.1.3.7.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
8.5

0.41
4.1.3.8 Electrical Bulb (40 Watt 3 hours sample)

Table 4.1.3.8.1: Weight variation test of 3 hours sample (Tablet) of 40 watt electrical bulb
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.098
0.0039
4.1
2
0.0923
-0.0018
1.9
3
0.0972
0.0031
3.3
4
0.094
-0.0001
0.1
5
0.0941
0.0952
0.0011
1.7
6
0.0923
-0.0018
1.9
7
0.0925
-0.0016
1.7
8
0.0949
0.0008
0.9
9
0.0922
-0.0019
2
10
0.0921
-0.002
2.1

Photolytic Degradation of Flupentixol-Melitracen

46

Figure 4.1.3.8.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit. This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and Xaxis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters
Table 4.1.3.8.2: Thickness test of 3 hours sample (Tablet) of 40 watt electrical bulb
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),i.e.(M+V) cm
1
0.8
0.03
0.83
2
0.8
0.03
0.83
3
0.8
0.03
0.83
4
0.8
0.03
0.83
5
0.8
0.03
0.83
6
0.8
0.03
0.83
7
0.8
0.03
0.83
8
0.8
0.03
0.83
9
0.85
0.03
0.88
10
0.8
0.03
0.83

Photolytic Degradation of Flupentixol-Melitracen

47

Figure 4.1.3.8.2: Thickness of tablets
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.8.3: Hardness test of 3 hours sample (Tablet) of 40 watt electrical bulb
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
5.8
5.2
2
5
5.2
3
4.8
5.2

Figure 4.1.3.8.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.

Photolytic Degradation of Flupentixol-Melitracen

48

Table 4.1.3.8.4: Friability test of 3 hours sample (Tablet) of 40 watt electrical bulb
Initial weight
Weight after rotation
Weight loss
0.941

0.9361

0.50%

Figure 4.1.3.8.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight
4.1.3.9 Concentration/Potency
Table 4.1.3.9.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.506

0.546

Table 4.1.3.9.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
8.86
0.427

Photolytic Degradation of Flupentixol-Melitracen

49

4.1.3.10 Electrical bulb (40 watt 6 hours sample)
Table 4.1.3.10.1: Weight variation test of 6 hours sample (Tablet) of 40 watt electrical bulb
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0942
-0.00005
0.1
2
0.0917
-0.00255
2.7
3
0.0971
0.00285
3
4
0.0939
-0.00035
0.4
5
0.09425
0.0923
-0.00195
2.1
6
0.0954
0.00115
1.2
7
0.0952
0.00095
1
8
0.0967
0.00245
2.6
9
0.0916
-0.00265
2.8
10
0.0944
0.00015
0.2

Figure 4.1.3.10.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.

Photolytic Degradation of Flupentixol-Melitracen

50

Table 4.1.3.10.2: Thickness test of 6 hours sample (Tablet) of 40 watt electrical bulb
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),i.e.(M+V) cm
1
0.85
0.03
0.88
2
0.75
0.0285
0.7785
3
0.75
0.0285
0.7785
4
0.85
0.03
0.88
5
0.8
0.03
0.83
6
0.8
0.03
0.83
7
0.8
0.03
0.83
8
0.8
0.03
0.83
9
0.75
0.0285
0.7785
10
0.75
0.0285
0.7785

Figure 4.1.3.10.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification. It has found that the thickness varies from tablet to tablet.
Table 4.1.3.10.3: Hardness test of 6 hours sample (Tablet) of 40 watt electrical bulb
Tablet no.
Hardness(kg)
Hardness Average (kg)
1

3.2

3.33

2

3.2

3.33

3

3.6

3.33

Photolytic Degradation of Flupentixol-Melitracen

51

3.7
3.6

3.5
Hardness(kg)

3.4
3.3

Hardness Averege
(kg)

3.2
3.1
3

1

2

3

Figure 4.1.3.10.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets do not meet the criteria of USP standard.
Because, USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.10.4: Friability test of 6 hours sample (Tablet) of 40 watt electrical bulb
Initial weight
Weight after rotation
Weight loss
0.9425

0.9417

0.08%

Figure 4.1.3.10.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,

Photolytic Degradation of Flupentixol-Melitracen

52

Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.11 Concentration/Potency
Table 4.1.3.11.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.471
0.507
Table 4.1.3.11.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
8.67
0.418
4.1.3.12 Electrical bulb (40 watt 9 hours sample)
Table 4.1.3.12.1: Weight variation test of 9 hours sample (Tablet) of 40 watt electrical bulb
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0938
-0.00087
0.9
2
0.0926
-0.00207
2.19
3
0.094
-0.00067
0.7
4
0.0914
-0.00327
3.45
5
0.09467
0.0917
-0.00297
3.1
6
0.0977
0.00303
3.2
7
0.0962
0.00153
1.6
8
0.0956
0.00093
0.98
9
0.095
0.00033
0.3
10
0.0987
0.00403
4.26

Photolytic Degradation of Flupentixol-Melitracen

53

Figure 4.1.3.12.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.
Table 4.1.3.12.2: Thickness test of 9 hours sample (Tablet) of 40 watt electrical bulb
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),
1
0.9
0.0285
0.9285
2
0.9
0.0285
0.9285
3
0.85
0.0285
0.8785
4
0.95
0.0285
0.9785
5
0.8
0.0285
0.8285
6
0.85
0.0285
0.8785
7
0.9
0.0285
0.9285
8
0.9
0.0285
0.9285
9
0.9
0.0285
0.9285
10
0.9
0.0285
0.9285

Photolytic Degradation of Flupentixol-Melitracen

54

Figure 4.1.3.12.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.12.3: Hardness test of 9 hours sample (Tablet) of 40 watt electrical bulb
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
2.7
2.73
2
2.5
2.73
3
3
2.73

Figure 4.1.3.12.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets do not meet the criteria of USP standard.
Because, USP specifies that hardness of any tablets must not be lower than 4 kg.

Photolytic Degradation of Flupentixol-Melitracen

55

Table 4.1.3.12.4: Friability test of 9 hours sample (Tablet) of 40 watt electrical bulb
Initial weight
Weight after rotation
Weight loss
0.9467

0.9435

0.30%

Figure: 4.1.3.12.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.13 Concentration/Potency
Table 4.1.3.13.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.468
0.504
Table 4.1.3.13.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
8.63
0.416

Photolytic Degradation of Flupentixol-Melitracen

56

4.1.3.14 Sunlight Exposure (3 hours)
Table 4.1.3.14.1: Weight variation test of 3 hours sample (Tablet) of sunlight exposure
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0937
0.00017
0.2
2
0.0916
-0.00193
2.1
3
0.0949
0.00137
1.5
4
0.0921
-0.00143
1.5
5
0.09353
0.0925
-0.00103
1.1
6
0.0936
0.00007
0.1
7
0.0927
-0.00083
0.9
8
0.0951
0.00157
1.7
9
0.0933
-0.00023
0.2
10
0.0958
0.00227
2.4

Figure 4.1.3.14.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.

Photolytic Degradation of Flupentixol-Melitracen

57

Table 4.1.3.14.2: Thickness test of 3 hours sample (Tablet) of sunlight exposure
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),
1
0.65
0.0275
0.6775
2
0.6
0.0275
0.6275
3
0.6
0.0275
0.6275
4
0.65
0.0275
0.6775
5
0.65
0.0275
0.6775
6
0.65
0.0275
0.6775
7
0.65
0.0275
0.6775
8
0.65
0.0275
0.6775
9
0.6
0.0275
0.6275
10
0.6
0.0275
0.6275

Figure 4.1.3.14.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.14.3: Hardness test of 3 hours sample (Tablet) of sunlight exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
5.8
2
5.5
5.36
3
4.8

Photolytic Degradation of Flupentixol-Melitracen

58

Figure 4.1.3.14.3: Hardness of Flupentixol-Melitracen (Fluxit). This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard. According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.14.4: Friability test of 3 hours sample (Tablet) of sunlight exposure
Initial weight
Weight after rotation
Weight loss
0.9353

0.9351

0.02%

Figure 4.1.3.14.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.

Photolytic Degradation of Flupentixol-Melitracen

59

4.1.3.15 Potency/ concentration
Table 4.1.3.15.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.557

0.602

Table 4.1.3.15.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
10.33

0.497

4.1.3.16 Sunlight exposure (6 hours)
Table 4.1.3.16.1: Weight variation test of 6 hours sample (Tablet) of sunlight exposure
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0933
0.00014
0.2
2
0.0917
-0.00146
1.6
3
0.0908
-0.00236
2.5
4
0.0942
0.00104
1.1
5
0.09316
0.0911
-0.00206
2.2
6
0.0965
0.00334
3.6
7
0.0891
-0.00406
4.3
8
0.0953
0.00214
2.3
9
0.0952
0.00204
2.2
10
0.0944
0.00124
1.3

Figure 4.1.3.16.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.

Photolytic Degradation of Flupentixol-Melitracen

60

This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.
Table 4.1.3.16.2: Thickness test of 6 hours sample (Tablet) of sunlight exposure
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(M+V cm),
1
0.6
0.0275
0.6275
2
0.6
0.0275
0.6275
3
0.6
0.0275
0.6275
4
0.5
0.0275
0.5275
5
0.55
0.0275
0.5775
6
0.5
0.0275
0.5275
7
0.6
0.0275
0.6275
8
0.6
0.0275
0.6275
9
0.6
0.0275
0.6275
10
0.6
0.0275
0.6275

Figure 4.1.3.16.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.

Photolytic Degradation of Flupentixol-Melitracen

61

Table 4.1.3.16.3: Hardness test of 6 hours sample (Tablet) of sunlight exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
5.9
2
6
5.56
3
4.8

Figure 4.1.3.16.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.16.4: Friability test of 6 hours sample (Tablet) of sunlight exposure
Initial weight
Weight after rotation
Weight loss
0.9316
0.9295
0.25%

Figure 4.1.3.16.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.

Photolytic Degradation of Flupentixol-Melitracen

62

This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.17 Concentration/ Potency
Table 4.1.3.17.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.538

0.581

Table 4.1.3.17.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
10.05

0.484
4.1.3.18 Sunlight exposure (9 hours sample)

Table 4.1.3.18.1: Weight variation test of 9 hours sample (Tablet) of sunlight exposure
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0946
0.00214
2.3
2
0.0932
0.00074
0.8
3
0.0927
0.00024
0.3
4
0.0918
-0.00066
0.7
5
0.09246
0.0908
-0.00166
1.8
6
0.0958
0.00334
3.6
7
0.0923
-0.00016
0.1
8
0.0897
-0.00276
3
9
0.0925
0.00004
0.04
10
0.0912
-0.00126
1.4

Photolytic Degradation of Flupentixol-Melitracen

63

Figure 4.1.3.18.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.
Table 4.1.3.18.2: Thickness test of 9 hours sample (Tablet) of sunlight exposure
Tablet Main scale Vernier scale Thickness of the tablets no. reading(cm), M reading(cm), V
(cm),
1
0.6
0.0275
0.6275
2
0.65
0.0275
0.6775
3
0.65
0.0275
0.6775
4
0.65
0.0275
0.6775
5
0.7
0.0275
0.7275
6
0.5
0.0275
0.5275
7
0.55
0.0275
0.5775
8
0.65
0.0275
0.6275
9
0.6
0.0275
0.6275
10
0.5
0.0275
0.5275

Photolytic Degradation of Flupentixol-Melitracen

64

Figure 4.1.3.18.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.18.3: Hardness test of 9 hours sample (Tablet) of sunlight exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
6.2
2
4.8
5.67
3

5.4

Figure 4.1.3.18.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates

Photolytic Degradation of Flupentixol-Melitracen

65

the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.18.4: Friability test of 9 hours sample (Tablet) of sunlight exposure
Initial weight
Weight after rotation
Weight loss
0.9246

0.9244

0.02%

Figure 4.1.3.18.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight.
4.1.3.19 Concentration/Potency
Table 4.1.3.19.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.413
0.444
Table: 4.1.3.19.1: Concentration of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
7.46
0.36

Photolytic Degradation of Flupentixol-Melitracen

66

4.1.3.20 Normal Light Exposure (14 Days)
Table 4.1.3.20.1: Weight variation test of 2 weeks (14 days) sample (Tablet) of normal light exposure Tablet Average initial Final weight, Weight variation, weight variation no. weight, Iav (gm)
F (gm)
F~Iav (gm)
(F~Iav/Iav)*x100
1
0.095
0.00067
0.70%
2
0.0945
0.00017
0.18%
3
0.0936
-0.00073
0.78%
4
0.0954
0.00107
1%
5
0.09433
0.0924
0.00193
2%
6
0.0969
0.00257
2.70%
7
0.0927
-0.00163
1.70%
8
0.0922
0.00213
2.26%
9
0.0935
0.00083
0.90%
10
0.0971
0.00277
2.90%

Figure 4.1.3.20.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.

Photolytic Degradation of Flupentixol-Melitracen

67

Table 4.1.3.20.2: Thickness test of 2 weeks sample (Tablet) of normal light exposure
Tablet Main scale Vernier scale Thickness of the tablets (cm), no. reading(cm), M reading(cm), V
i.e.(M+V) cm
1
0.6
0.275
0.6275
2
0.6
0.275
0.6275
3
0.6
0.275
0.6275
4
0.6
0.275
0.6275
5
0.6
0.275
0.6275
6
0.6
0.275
0.6275
7
0.6
0.275
0.6275
8
0.6
0.275
0.6275
9
0.6
0.275
0.6275
10
0.6
0.275
0.6275

Thickness of tablet

Thickness of the tablets (cm),
i.e.(M+V) cm
0.8
0.6
0.4

Thickness of the tablets (cm),
i.e.(M+V) cm

0.2
0
1

2

3

4

5

6

7

8

9 10 11

Number of tablets

Figure 4.1.3.20.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.20.3: Hardness test of 2 weeks sample (Tablet) of normal light exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
6
2
6
6.17
3
6.5

Photolytic Degradation of Flupentixol-Melitracen

68

Figure 4.1.3.20.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.20.4: Friability test of 2 weeks sample (Tablet) of normal light exposure
Initial weight
Weight after rotation
Weight loss
0.9433

0.9429

0.04%

Figure 4.1.3.20.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,

Photolytic Degradation of Flupentixol-Melitracen

69

Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight
4.1.3.21 Potency/Concentration
Table 4.1.3.21.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.68
0.741
Table 4.1.3.21.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
13.29

0.639

4.1.3.22 Normal light exposure (28 days)
Table 4.1.3.22.1: Weight variation test of 4 weeks sample (Tablet) of normal light exposure
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0921
-0.00243
2.6
2
0.094
-0.00053
0.6
3
0.0951
0.00057
0.6
4
0.0957
0.00117
1.2
5
0.09453
0.0926
-0.00193
2
6
0.0957
0.00117
1.2
7
0.0954
0.00087
0.9
8
0.0974
0.00287
3
9
0.0944
-0.00013
0.1
10
0.0929
-0.00163
1.7

Photolytic Degradation of Flupentixol-Melitracen

70

Figure 4.1.3.22.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.
Table 4.1.3.22.2: Thickness test of 4 weeks sample (Tablet) of normal light exposure
Tablet Main scale Vernier scale Thickness of the tablets (cm), i.e. no. reading(cm), M reading(cm), V
(M+V) cm
1
0.6
0.0275
0.6275
2
0.6
0.0275
0.6275
3
0.6
0.0275
0.6275
4
0.6
0.0275
0.6275
5
0.6
0.0275
0.6275
6
0.6
0.0275
0.6275
7
0.65
0.0275
0.6775
8
0.65
0.0275
0.6775
9
0.65
0.0275
0.6775
10
0.65
0.0275
0.6775

Photolytic Degradation of Flupentixol-Melitracen

71

Figure 4.1.3.22.2: Thickness of tablets.
This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP,
Batch passed the specification.
Table 4.1.3.22.3: Hardness test of 4 weeks sample (Tablet) of normal light exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1
5.3
2
6.6
6
3
6.2

Figure 4.1.3.22.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.

Photolytic Degradation of Flupentixol-Melitracen

72

Table 4.1.3.22.4: Friability test of 4 weeks sample (Tablet) of normal light exposure
Initial weight
Weight after rotation
Weight loss
0.9453

0.9442

0.12%

Figure 4.1.3.22.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,
Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight
4.1.3.23 Concentration/Potency
Table 4.1.3.23.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.68

0.737

Table 4.1.3.23.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
12.2

0.589

Photolytic Degradation of Flupentixol-Melitracen

73

4.1.3.24 Normal light exposure (6 weeks)
Table 4.1.3.24.1: Weight variation test of 6 weeks sample (Tablet) of normal light exposure
Tablet Average initial Final
Weight variation, % weight variation no. weight, Iav (gm) weight, F F~Iav (gm)
(F~Iav/Iav)*x100
(gm)
1
0.0938
0.00142
1.54
2
0.0933
0.00092
0.996
3
0.0897
-0.00208
2.25
4
0.0939
0.00152
1.65
5
0.09238
0.0938
0.00142
1.54
6
0.0914
-0.00098
1.06
7
0.0937
0.00132
1.43
8
0.0925
0.00013
0.14
9
0.0914
-0.00098
1.06
10
0.0915
-0.00088
0.95

Figure 4.1.3.24.1: Line chart of %weight variation of Flupentixol-Melitracen, Brand: Fluxit.
This graph provides information about the individual % weight variation of Fluxit tablet. The line chart is showing % weight variation. Y axis is indicating individual % weight variation and
X-axis indicating the number of tablets. According to BP all the tablets comply with all specification. No tablets exceed ± 5 % variation. That means the Batch of Fluxit has passed the
QC parameters.

Photolytic Degradation of Flupentixol-Melitracen

74

Table 4.1.3.24.2: Thickness test of 6 weeks sample (Tablet) of normal light exposure
Tablet Main scale Vernier scale Thickness of the tablets (cm), i.e. no. reading(cm), M reading(cm), V
(M+V) cm
1
0.55
0.0275
0.5775
2
0.5
0.0275
0.5275
3
0.6
0.0275
0.6275
4
0.6
0.0275
0.6275
5
0.55
0.0275
0.5775
6
0.6
0.0275
0.6275
7
0.55
0.0275
0.5775
8
0.6
0.0275
0.6275
9
0.6
0.0275
0.6275
10
0.6
0.0275
0.6275

Figure 4.1.3.24.2: Thickness of tablets. This graph provides information about the thickness of the individual tablet. Y- Axis indicates the thickness of the tablets and X-axis indicates the number of the tablets. According to USP, Batch passed the specification.
Table 4.1.3.24.3: Hardness test of 6 weeks sample (Tablet) of normal light exposure
Tablet no.
Hardness(kg)
Hardness Average (kg)
1

6.2

2

6.6

3

5.5

6.1

Photolytic Degradation of Flupentixol-Melitracen

75

Figure 4.1.3.24.3: Hardness of Flupentixol-Melitracen (Fluxit).
This graph provides information about the hardness of 3 tablets and average hardness of the tablets. The blue colored bar chart indicates hardness of 3 tablets and the red color chart indicates the average hardness (kg) of 3 tablets. All the tablets meet the criteria of USP standard.
According to USP all the tablets passed the specification. USP specifies that hardness of any tablets must not be lower than 4 kg.
Table 4.1.3.24.4: Friability test of 6 weeks sample (Tablet) of normal light exposure
Initial weight
Weight after rotation
Weight loss
0.9238

0.9227

0.12%

Figure 4.1.3.24.4: Bar chart showing percent friability of Flupentixol-Melitracen. Brand: Fluxit.
This graph provides information of difference of weight in friability test. The bar chart is indicating final weight of ten tablets and weight after rotation of 10 tablets. According to USP,

Photolytic Degradation of Flupentixol-Melitracen

76

Batch passed the specification. USP specifies that if friability study is performed with ten tablets of any batch they must not lose 1% of their initial weight
4.1.3.25 Concentration/Potency
Table 4.1.3.25.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance
0.658

0.713

Table 4.1.3.25.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance
12.4

0.595
4.1.3.26 Difference in Concentration and Absorbance in control sample
Table 4.1.3.26.1: Concentration and Absorbance of Flupentixol dihydrochloride
Control
Concentration (mg/ml)
Absorbance
Control 1

0.74

0.802

Control 2

0.699

0.758

In here, we found column diagram where we saw that concentration of Flupentixol dihydrochloride of Fluxit almost same.

Figure4.1.3.26.1: Column showing the difference concentration of control sample

Photolytic Degradation of Flupentixol-Melitracen

77

Table 4.1.3.26.2: Concentration and Absorbance of Melitracen hydrochloride
Control
Concentration (mg/ml)
Absorbance
Control 1

13.78

0.662

Control 2

13.6

0.653

In here, we found column diagram where we saw that concentration Melitracen hydrochloride of
Fluxit almost same

Figure 4.1.3.26.2: Column showing the concentration of control sample
4.1.3.27 Difference in Concentration and Absorbance in each 3 Hour time interval for
Sample that was kept under of 25 watts Electrical Bulb
Table 4.1.3.27.1: Concentration and Absorbance of Flupentixol dihydrochloride
Time
Concentration (mg/ml) Absorbance
3 hours
0.68
0.737
6 hours
0.477
0.514
9 hours
0.476
0.513
In here, we found column diagram where we saw that concentration of Flupentixol dihydrochloride of Fluxit decreases in each three hour time interval

Photolytic Degradation of Flupentixol-Melitracen

78

Figure 4.1.3.27.1: Column showing the difference in Concentration after each 3 Hour time interval for Flupentixol dihydrochloride

Time

Table 4.1.3.27.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance

3 hours

11.9

0.57

6 hours

7.3

0.354

9 hours

8.5

0.41

In here, we found column diagram where we saw that concentration Melitracen hydrochloride of
Fluxit decreases in each three hour time interval

Figure 4.1.3.27.2: Column showing the difference in Concentration after each 3 Hour time interval for Melitracen hydrochloride

Photolytic Degradation of Flupentixol-Melitracen

79

4.1.3.28 Sample that was kept under of 40 watt Electrical Bulb

Time

Table 4.1.3.28.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance

3 hours

0.506

0.546

6 hours

0.471

0.507

9 hours

0.468

0.504

In here, we found column diagram where we saw that concentration of Flupentixol dihydrochloride of Fluxit decreases in each three hour time interval

Figure 4.1.3.28.1: Difference in Concentration after each 3 Hour time interval for Flupentixol dihydrochloride Time

Table 4.1.3.28.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance

3 hours

8.86

0.427

6 hours

8.67

0.418

9 hours

8.63

0.416

In here, we found column diagram where we saw that concentration Melitracen hydrochloride of
Fluxit decreases in each three hour time interval

Photolytic Degradation of Flupentixol-Melitracen

80

Figure 4.1.3.28.2: Difference in Concentration after each 3 Hour time interval for Melitracen hydrochloride 4.1.3.29 Sample that was kept under Sunlight exposure
Table 4.1.3.29.1: Concentration and Absorbance of Flupentixol dihydrochloride
Time
Concentration (mg/ml)
Absorbance
3 hours
0.557
0.602
6 hours

0.538

0.581

9 hours

0.413

0.444

In here, we found column diagram where we saw that concentration of Flupentixol dihydrochloride of Fluxit decreases in each three hour time interval

Figure 4.1.3.29.1: Difference in Concentration after each 3 Hour time interval for Flupentixol dihydrochloride Photolytic Degradation of Flupentixol-Melitracen

Time

81

Table 4.1.3.29.2: Concentration and Absorbance of Melitracen hydrochloride
Concentration (mg/ml)
Absorbance

3 hours

10.33

0.497

6 hours

10.05

0.484

9 hours

7.46

0.36

In here, we found column diagram where we saw that concentration of Melitracen hydrochloride of Fluxit decreases in each three hour time interval

Figure 4.1.3.29.2: Difference in Concentration after each 3 Hour time interval for Melitracen hydrochloride 4.1.3.30 Difference in Concentration and Absorbance for the Sample prepared on Room temperature for stability testing: Preservation of sample started at 23rd February 2012

Time

Table 4.1.3.30.1: Concentration and Absorbance of Flupentixol dihydrochloride
Concentration (mg/ml)
Absorbance

14 days

0.68

0.741

28 days

0.68

0.737

42 days

0.658

0.713

In here, we found column diagram where we saw that concentration of Flupentixol dihydrochloride of Fluxit decreases in each days interval

Photolytic Degradation of Flupentixol-Melitracen

82

Figure 4.1.3.30.1: Difference in Concentration after days interval for Flupentixol dihydrochloride Table 4.1.3.30.2: Concentration and Absorbance of Melitracen hydrochloride
Time
Concentration (mg/ml)
Absorbance
14 days

13.29

0.639

28days

12.2

0.589

42 days

12.4

0.595

In here, we found column diagram where we saw that concentration of Melitracen hydrochloride of Fluxit decreases in days time interval

Figure 4.1.3.30.2: difference in Concentration after days interval for Melitracen hydrochloride

Photolytic Degradation of Flupentixol-Melitracen

83

4.2 Discussion
In our experiment it was observed that the concentration of Flupentixol dihydrochloride and
Melitracen hydrochloride was decreased gradually in various light condition like under 25 and
40 watt electrical bulb, sunlight, normal light (room temperature) exposure condition.
The sample was kept under that was Fluxit under 25 and 40 watt electrical bulb condition. We carried out test every three hours after exposed the sample under electrical bulb. We observed that the concentration of Flupentixol dihydrochloride and Melitracen hydrochloride was decreased gradually. It was found that the nine hours sample had the less concentration than six hours and six hours sample had the less concentration than the three hours exposed condition.
It was also found the same result after sunlight and normal room temperature exposure condition.
So we can say that the Fluxit containing combination of Flupentixol dihydrochloride and
Melitracen hydrochloride is light sensitive and the potency is decreased after light exposure.

Photolytic Degradation of Flupentixol-Melitracen

Chapter Five
Conclusion

84

Photolytic Degradation of Flupentixol-Melitracen

85

CONCLUSION
In this study it was observed that the physical parameter like weight variation, friability, hardness, thickness have passed the USP and BP specification. But there were remarkable changes in concentration/potency. The concentration of Flupentixol dihydrochloride and
Melitracen hydrochloride was decreased gradually after exposure in 25 and 40 watt electrical light condition, sunlight and normal light exposure (room temperature) condition. In this study it was also observed that hardness of six and nine hours 40 watt exposure sample do not meet the
USP specification. So we can say that the Fluxit containing combination of Flupentixol dihydrochloride and Melitracen hydrochloride is light sensitive and the potency is decreased after light exposure.

Photolytic Degradation of Flupentixol-Melitracen

Chapter Six
References

86

Photolytic Degradation of Flupentixol-Melitracen

87

REFERENCES
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Kumari, S. et al. (2010) ‘Spectrophotometric methods for simultaneous estimation of Flupentixol
Dihydrochloride and Melitracen Hydrochloride in combined tablet dosage form.’ Journal of
Chemical and Pharmaceutical Research, J. Chem. Pharm. Res., 2010, 2(3):158-171.
Lakshminarayana, B. (2011) ‘Development and validation Methods for the Estimation of
Flupenthixol dihydrochloride in bulk and pharmaceutical Dosage Form.’ Rajiv Gandhi
University
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