Kader A, Jalil R
Faculty of Pharmacy, University of Dhaka, Bangladesh.
Drug Dev Ind Pharm. 1999 Feb;25(2):141-51. doi: 10.1081/ddc-100102154.
A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.
使用低分子量（MW）的DL-聚乳酸和高分子量的L-聚乳酸（PLA）聚合物制备了苯巴比妥（PB）微胶囊片的缓释（SR）制剂。PB的微囊化显示微胶囊的单峰尺寸分布（375至550微米），具有高负载量（>84%）。微胶囊中的药物释放受聚合物比例影响，并随L-PLA量的增加而增加。PB与PLA的微胶囊和物理混合物分别直接独立压片，形成微胶囊片和基质片。与基质片或游离微胶囊相比，微胶囊片的药物释放显著降低（p<.001）（游离微胶囊>基质>微胶囊片）。我们还研究了片剂辅料、压缩压力和微胶囊载药量对片剂性能的影响，包括脆碎度、硬度、孔隙率、拉伸强度和PB的释放动力学。在使用Emcompress或乳糖的情况下，药物释放速率随压缩压力的增加而增加，但使用Avicel时则不然。与没有崩解剂的片剂相比，羟丙基淀粉钠可使药物释放速率提高三至五倍。随着微胶囊载药量的增加，药物释放速率降低；然而，片剂性能仍然令人满意。在片剂溶解和崩解后，通过显微镜监测微胶囊的形态。由于微胶囊壁的机械破坏，片剂的压缩压力和微胶囊载药量会加速药物释放，这在片剂崩解和溶解后更明显。我们的数据表明，PLA微胶囊可以压片制成SR产品，而不会显著影响其释放动力学。
