Permeability Of Amorphous Form Of Indomethacin Case Study
The aim of this thesis project is to study in vitro the permeability of amorphous drug systems in different conditions.
First, three complementary techniques are performed to characterize the crystalline and amorphous form of indomethacin. These techniques include IR spectroscopy, Raman spectroscopy and differential scanning calorimetry.
Indomethacin is a compound belonging to class II of the BCS and is consequently a poorly water-soluble drug. The limiting step in order to have a good bioavailability is the dissolution step. Several possibilities can be applied to improve the dissolution step and hence the bioavailability, such as nanocrystalline and amorphous formulations.
The amorphous form exhibits a higher solubility in comparison with crystalline forms. …show more content…
MATERIALS AND METHODS
1.1. MATERIALS
The γ form of indomethacin was obtained from Orion Pharma (Helsinki, Finland). Potassium phthalate monobasic (Sigma Aldrich, Steinheim, Germany), sodium hydroxide (Eka Nobel, Bohus, Sweden), HPMC E5 (Dow chemical Company, Michigan, USA), Soluplus® (BASF, Ludwigshafen, Germany) and ethanol 99.5% (Altia Oy, Rajamäki, Finland) were used as received.
1.2. METHODS
1.2.1. Preparation of amorphous indomethacin
Amorphous indomethacin was prepared by spreading a thin layer of the crystalline powder on an aluminium pan. The aluminium pan was heated at 165 °C on a hot plate. The melt was then cooled down to room temperature by placing the pan on a cold metal surface.
(To prepare a solid dispersion, equal quantities of the γ form of indomethacin and a polymer were weighed. The amounts were mixed in a mortar and pestle to obtain a homogeneous mixture of indomethacin and polymer at a 1:1 ratio (w/w). This mixture was spread on an aluminium pan, heated at 165 °C and cooled down as described before in the procedure to prepare amorphous indomethacin. The polymers used in this study are Soluplus® and HPMC.)
1.2.2. Solid state characterization
1.2.2.1. Infrared
First, three complementary techniques are performed to characterize the crystalline and amorphous form of indomethacin. These techniques include IR spectroscopy, Raman spectroscopy and differential scanning calorimetry.
Indomethacin is a compound belonging to class II of the BCS and is consequently a poorly water-soluble drug. The limiting step in order to have a good bioavailability is the dissolution step. Several possibilities can be applied to improve the dissolution step and hence the bioavailability, such as nanocrystalline and amorphous formulations.
The amorphous form exhibits a higher solubility in comparison with crystalline forms. …show more content…
MATERIALS AND METHODS
1.1. MATERIALS
The γ form of indomethacin was obtained from Orion Pharma (Helsinki, Finland). Potassium phthalate monobasic (Sigma Aldrich, Steinheim, Germany), sodium hydroxide (Eka Nobel, Bohus, Sweden), HPMC E5 (Dow chemical Company, Michigan, USA), Soluplus® (BASF, Ludwigshafen, Germany) and ethanol 99.5% (Altia Oy, Rajamäki, Finland) were used as received.
1.2. METHODS
1.2.1. Preparation of amorphous indomethacin
Amorphous indomethacin was prepared by spreading a thin layer of the crystalline powder on an aluminium pan. The aluminium pan was heated at 165 °C on a hot plate. The melt was then cooled down to room temperature by placing the pan on a cold metal surface.
(To prepare a solid dispersion, equal quantities of the γ form of indomethacin and a polymer were weighed. The amounts were mixed in a mortar and pestle to obtain a homogeneous mixture of indomethacin and polymer at a 1:1 ratio (w/w). This mixture was spread on an aluminium pan, heated at 165 °C and cooled down as described before in the procedure to prepare amorphous indomethacin. The polymers used in this study are Soluplus® and HPMC.)
1.2.2. Solid state characterization
1.2.2.1. Infrared