Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation

被引:45
作者
Ali, Ahmed Mahmoud Abdelhaleem [1 ,2 ]
Ali, Adel Ahmed [1 ]
Maghrabi, Ibrahim Abdullah [2 ]
机构
[1] Beni Suef Univ, Fac Pharm, Dept Pharmaceut, Bani Suwayf, Egypt
[2] Taif Univ, Fac Pharm, Dept Clin Pharm, Al Huwaya, Saudi Arabia
关键词
clozapine; carboxylic acids; co-amorphous systems; plasticizer; WATER-SOLUBLE DRUGS; SOLID DISPERSIONS; PHASE-BEHAVIOR; CITRIC-ACID; IN-VITRO; SOLUBILITY; CRYSTAL; RELEASE; IMPROVE; INDOMETHACIN;
D O I
10.1515/acph-2015-0014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1: 1, 1: 1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1: 2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1: 1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism.
引用
收藏
页码:133 / 146
页数:14
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