Barzegar-Jalali Mohammad, Dastmalchi Siavoush
Department of Pharmaceutics, School of Pharmacy and Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Dev Ind Pharm. 2007 Jan;33(1):63-70. doi: 10.1080/03639040600762636.
Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition technique using two grades of microcrystalline cellulose as carrier materials with different ratios of drug to carrier. The dissolution rate of chlorpropmide from the SDs was carried out at two physiological pH values of 1.1 and 7.25 simulating gastric and intestinal environments. The dissolution was dependent on the grade, the ratio of drug to carrier and pH. The higher dissolution was observed for more hydrophilic grade of the carrier as well as the higher ratio of carrier to drug. At the higher pH the drug dissolved much faster than the lower pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas infrared spectroscopy revealed no drug interactions with solvent and the carriers. The enhanced dissolution was attributed to the reduced drug crystallinity, decreased particle size, increased wettability and reduced aggregation of the hydrophobic drug particles. A novel model denoted as reciprocal powered time model with its theoretical justification was employed to analyze the dissolution data and proved to be superior to commonly used models for the analysis of the data. There was a quantitative relation between the model parameter and the ratio of carrier to drug which could be of value in dissolution rate prediction.
采用溶剂沉积技术，以两种不同等级的微晶纤维素为载体材料，制备了不同药物与载体比例的氯磺丙脲固体分散体（SDs）。在模拟胃和肠道环境的两个生理pH值（1.1和7.25）下，测定了氯磺丙脲从SDs中的溶出速率。溶出度取决于载体等级、药物与载体的比例以及pH值。对于更亲水等级的载体以及更高的载体与药物比例，观察到更高的溶出度。在较高pH值下，药物溶解比在较低pH值下快得多。X射线衍射显示SDs中药物结晶度有所降低，而红外光谱表明药物与溶剂和载体之间没有相互作用。溶出度的提高归因于药物结晶度降低、粒径减小、润湿性增加以及疏水性药物颗粒聚集减少。采用一种新的模型——倒数幂时间模型及其理论依据来分析溶出数据，结果证明该模型在分析数据方面优于常用模型。模型参数与载体与药物的比例之间存在定量关系，这对于预测溶出速率可能具有价值。
