Midazolam Lab Report

Results and discussion

The aqueous solubility of midazolam is a function of both the imidazobenzodiazepine ring opening, which is a fully reversible process, and the ionization of the drug molecule play an important role in the supramolecular complexation with water-soluble cyclodextrins (Loftsson et al., 2001). Therefore, the total charges were assessed from the acid dissociation constant determined for different forms of midazolam as depicted in Figure 1. First, predicted negative decimal logarithm of acid dissociation constant ( and) and degree of dissociation for different forms of midazolam (Figure 1 (A)) were calculated by using the MarvinSketch software (ChemAxon, Budapest, Hungary), and equations 1 and 2 considering the charge-contributing functional groups for predicting molecular macrospecies distribution (88.29% for OR and 86% for CR) at physiological pH (Supplementary material 1). It was already experimentally determined for benzodiazepines that the positively charged nitrogen atom () = 7.0) has been affected by the pH-dependent reaction, hence the diazepine ring (1,4-benzodiazepine moiety) was formed with of 2.4 (Cho et al., 1983; Loftsson et al., 2001). In addition, the basic nitrogen in position 2 of the imidazole ring (imidazobenzodiazepine moiety) allows the active elements of
Given that methods like AutoDock have a typical error of ±2 kcal*mol-1, which might produce a huge deviation of ΔGbind and Kb for the analysed compound (Cosconati et al., 2010), the midazolam-TRIMEB complexes, including OR-TRIMEB, TS-TRIMEB, and CR-TRIMEB, were subjected to the molecular docking with data collection for analysis from three different experiments (Table S1 and