Kader A, Jalil R
Faculty of Pharmacy, Dhaka University, Bangladesh.
Drug Dev Ind Pharm. 1998 Jun;24(6):527-34. doi: 10.3109/03639049809085653.
Poly(L-lactic acid), (L-PLA) pellets containing theophylline as a model drug were prepared with increasing bovine serum albumin (BSA) load of 10, 20, 30, 40, or 50% by direct compression. The drug release from pellets was studied in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. The annealing effect on theophylline release from pellets was also studied at 20, 30, 60, and 80 degrees C. In all cases, release kinetics followed the Higuchian mechanism with an initial burst effect followed by sustained release of theophylline during the experimental period. Increasing BSA load resulted in a linear increase in Higuchian release rates presumably because of the hydrophilic nature of BSA. Furthermore, BSA did not interact chemically with the polymer matrix and was held physically by the dense polymer matrix. However, drug release decreased with an increase in annealing temperature. Release of theophylline was higher from PLA-BSA combination pellets compared to PLA pellets at temperatures below the glass transition temperature (Tg) of the polymer and lower for temperatures above Tg. The temperature effect on drug release may be attributed to both the reduction of core solubility in the bulk phase and the lowering of diffusibility of the polymeric membrane. No drug-polymer interactions or polymer degradation was observed within the experimental setup when studied by differential scanning calorimetry (DSC), infrared (FTIR) spectroscopy, and gravimetric methods. DSC studies of pellets showed no hints of microstructural changes (crystallinity) of the polymers. In our experiments, theophylline was released primarily by leaching through channels and not by polymer degradation. The release rate was dependent on BSA loading and annealing. It may be concluded that PLA pellets can be fabricated suitably using BSA and annealing to design sustained-release preparations of water-soluble drugs.
通过直接压片法制备了含有茶碱作为模型药物的聚（L-乳酸）（L-PLA）微丸，牛血清白蛋白（BSA）负载量分别为10%、20%、30%、40%或50%且逐渐增加。在37℃的磷酸盐缓冲盐水（PBS，pH 7.4）中研究了微丸的药物释放情况。还在20℃、30℃、60℃和80℃下研究了退火对微丸中茶碱释放的影响。在所有情况下，释放动力学均遵循Higuchi机制，在实验期间，茶碱首先有一个突释效应，随后是持续释放。BSA负载量的增加导致Higuchi释放速率呈线性增加，这可能是由于BSA的亲水性。此外，BSA与聚合物基质没有化学相互作用，而是被致密的聚合物基质物理包裹。然而，药物释放随着退火温度的升高而降低。在聚合物的玻璃化转变温度（Tg）以下，PLA-BSA组合微丸中茶碱的释放量高于PLA微丸；在Tg以上则较低。温度对药物释放的影响可能归因于本体相中核心溶解度的降低以及聚合物膜扩散性的降低。通过差示扫描量热法（DSC）、红外（FTIR）光谱法和重量法研究发现，在实验设置范围内未观察到药物-聚合物相互作用或聚合物降解。微丸的DSC研究未显示聚合物微观结构变化（结晶度）的迹象。在我们的实验中，茶碱主要通过通道溶出释放，而非聚合物降解。释放速率取决于BSA负载量和退火。可以得出结论，使用BSA和退火可以适当地制备PLA微丸，以设计水溶性药物的缓释制剂。
