Barakat Nahla S, Elbagory Ibrahim M, Almurshedi Alanood S
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Drug Deliv. 2009 Jan;16(1):57-65. doi: 10.1080/10717540802518157.
The objective of this study was to investigate the effect of lipophilic (Compritol 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE%), and similarity factor (f(2) factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to Case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets.
本研究的目的是考察亲脂性成分(Compritol 888 ATO)和亲水性成分(羟丙甲纤维素与微晶纤维素的组合)对卡马西平从颗粒剂及相应片剂中释放的影响。采用湿法制粒后压片的方法制备颗粒剂和片剂。研究了基质的溶胀行为。将每种制剂的溶出曲线与卡马西平缓释片(得理多CR)的溶出曲线进行比较,并计算平均溶出时间(MDT)、溶出效率(DE%)和相似因子(f(2)因子)。结果发现,羟丙甲纤维素浓度的增加会导致颗粒剂释放速率降低,且颗粒剂难以实现零级释放。羟丙甲纤维素的用量对药物释放起主导作用。卡马西平从基质片剂制剂中的释放机制遵循非菲克扩散,随着羟丙甲纤维素含量的增加向第二类转运,表明溶蚀作用显著。药物载量的增加导致药物释放加速,且由于片剂水化延迟而呈现非理想的控释机制。这些结果表明,湿法制粒后压片可能是制备卡马西平缓释片的合适方法。