The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin ( α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). Th...The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin ( α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The interactions of drug-cyclodextrin in solution were investigated by the phase-solubility analysis. Diazepam (nitrazepam) content in aqueous complexation medium was analyzed UV spectrophotometrically. Classical solubility data were used to derive apparent stability constants (K1:1) which were used to derive thermodynamic parameters for the diazepam (nitrazepam)-cyclodextrin complexes. Since all phase solubility plots were of AL–types, and calculated Slopes after linear regression analysis were found to be less than 1, it could be assumed that stoichiometry of the formed binary systems was 1:1. According to the calculated K1:1 values, the stability of the complexes of diazepam and nitrazepam with a-CD, β-CD and 2-HP-β-CD varies as follows: 2-HP-β-CD > β-CD > β-CD. The a-CD has higher affinity for dissolving nitrazepam compared to diazepam. While all parameters lead to an improvement in solubility, the largest effect was obtained for guest-host complexation with 2-HP-β-CD. The solubility of diazepam and nitrazepam in water increased 93.02 times and 64.23 times, respectively, in the presence of 40% (w/w) 2-HP-β-CD, at 25°C. Solubility data for diazepam and nitrazepam in aqueous 2-HP-b-CD were used to derive thermodynamic parameters, ΔG° at 298 K = –14.43 kJ·mol–1, ΔH° = 0.79 kJ·mol–1, ΔS° at 298 K = 51.17 J·mol–1·K–1 and ΔG° at 298 K = –13.43 kJ·mol–1, ΔH° = 2.38 kJ·mol–1, ΔS° at 298 K = 53.01 J·mol–1·K–1, respectively. Formation of inclusion complexes substantially increases the water solubility of diazepam and nitrazepam. Diazepam and nitrazepam dissolution thermodynamics in aqueous 2-HP-β-CD were characterized by spontaneous and endothermic dissolution and hydrophobic interactions.展开更多
The metabolites and metabolic passways of nitrazepam in rat were confirmed.Wistar rats were feed a pill of nitrazepam,24 h urine reactions were collected.After β-Glucuronidase hydrolysis of the urine samples,the frac...The metabolites and metabolic passways of nitrazepam in rat were confirmed.Wistar rats were feed a pill of nitrazepam,24 h urine reactions were collected.After β-Glucuronidase hydrolysis of the urine samples,the fractions were extracted by Oasis HLB3cc solid-phase column and analyzed by gas chromatography-mass spectrometry with DB-35 MS column.7-Acetylaminonitrazepam,7-aminonitrazepam and 2-amino-5-nitrophenylphenylmethanone were identified as nitrazepam metabolites.The results suggested that two metabolic passways for nitrazepam may be operative in rat.The first passway leads to the corresponding 7-aminonimetazepam in which the amino group is subsequently acetylated.The second passway is open the parent compounds rings to 2-amino-5-nitrophenylphenylmethanone.Nitrazepam was metabolized quickly in rats and 7-acetylaminonitrazepam were the main metabolites in urine.展开更多
文摘The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin ( α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The interactions of drug-cyclodextrin in solution were investigated by the phase-solubility analysis. Diazepam (nitrazepam) content in aqueous complexation medium was analyzed UV spectrophotometrically. Classical solubility data were used to derive apparent stability constants (K1:1) which were used to derive thermodynamic parameters for the diazepam (nitrazepam)-cyclodextrin complexes. Since all phase solubility plots were of AL–types, and calculated Slopes after linear regression analysis were found to be less than 1, it could be assumed that stoichiometry of the formed binary systems was 1:1. According to the calculated K1:1 values, the stability of the complexes of diazepam and nitrazepam with a-CD, β-CD and 2-HP-β-CD varies as follows: 2-HP-β-CD > β-CD > β-CD. The a-CD has higher affinity for dissolving nitrazepam compared to diazepam. While all parameters lead to an improvement in solubility, the largest effect was obtained for guest-host complexation with 2-HP-β-CD. The solubility of diazepam and nitrazepam in water increased 93.02 times and 64.23 times, respectively, in the presence of 40% (w/w) 2-HP-β-CD, at 25°C. Solubility data for diazepam and nitrazepam in aqueous 2-HP-b-CD were used to derive thermodynamic parameters, ΔG° at 298 K = –14.43 kJ·mol–1, ΔH° = 0.79 kJ·mol–1, ΔS° at 298 K = 51.17 J·mol–1·K–1 and ΔG° at 298 K = –13.43 kJ·mol–1, ΔH° = 2.38 kJ·mol–1, ΔS° at 298 K = 53.01 J·mol–1·K–1, respectively. Formation of inclusion complexes substantially increases the water solubility of diazepam and nitrazepam. Diazepam and nitrazepam dissolution thermodynamics in aqueous 2-HP-β-CD were characterized by spontaneous and endothermic dissolution and hydrophobic interactions.
文摘The metabolites and metabolic passways of nitrazepam in rat were confirmed.Wistar rats were feed a pill of nitrazepam,24 h urine reactions were collected.After β-Glucuronidase hydrolysis of the urine samples,the fractions were extracted by Oasis HLB3cc solid-phase column and analyzed by gas chromatography-mass spectrometry with DB-35 MS column.7-Acetylaminonitrazepam,7-aminonitrazepam and 2-amino-5-nitrophenylphenylmethanone were identified as nitrazepam metabolites.The results suggested that two metabolic passways for nitrazepam may be operative in rat.The first passway leads to the corresponding 7-aminonimetazepam in which the amino group is subsequently acetylated.The second passway is open the parent compounds rings to 2-amino-5-nitrophenylphenylmethanone.Nitrazepam was metabolized quickly in rats and 7-acetylaminonitrazepam were the main metabolites in urine.
