Ravi Punna Rao, Ganga Sindhura, Saha Ranendra Narayan
Pharmacy Group, Faculty Division III, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
Chem Pharm Bull (Tokyo). 2008 Apr;56(4):518-24. doi: 10.1248/cpb.56.518.
Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.
采用不同比例和不同粘度等级的羟丙基甲基纤维素制备了齐多夫定口服控释骨架片。研究了聚合物比例、聚合物粘度和压力等各种制剂因素对药物体外释放的影响。体外释放研究采用美国药典(USP)1型装置(篮法),在900ml pH 6.8的磷酸盐缓冲液中,转速为100rpm。使用零级模型方程、Higuchi平方根方程和Ritger-Peppas经验方程分析释放动力学。研究了药物与所用各种制剂辅料的相容性。体外释放研究表明,释放速率随着聚合物比例和粘度等级的增加而降低。发现压力增加会降低药物释放速率。含有10%羟丙基甲基纤维素(HPMC)4000cps的骨架片在第一小时显示出21%的良好初始药物释放,并将释放延长至16小时。含有20% HPMC 4000cps和10% HPMC 15000cps的骨架片在第一小时释放18%,并将释放延长至20小时。释放动力学的数学分析表明,骨架片中药物的释放性质遵循非菲克或异常释放。在骨架片制剂中使用的药物和辅料之间未观察到不相容性。所研制的齐多夫定控释骨架片具有良好的初始释放(第一小时为17-25%),并将释放延长至16-20小时,可克服传统齐多夫定片的缺点。