Kader A, Jalil R
Faculty of Pharmacy, Dhaka University, Bangladesh.
Drug Dev Ind Pharm. 1998 Jun;24(6):535-9. doi: 10.3109/03639049809085654.
Poly(L-lactic acid) (L-PLA) pellets intended for either parenteral or oral use were successfully prepared by a direct compression technique without the use of heat or organic solvents. Salicylic acid and theophylline were chosen as drug candidates. The drug release from pellets was affected by the compression pressure. The Higuchi plots of the drugs showed a t1/2 dependent drug release pattern. The release rates of these drugs from PLA pellets were directly correlated to their solubilities in the dissolution media. At lower pH (< 7), the release of salicylic acid was found to be slower than theophylline; however, at higher pH (> 7), the release of salicylic acid was faster than that of the theophylline. The release rate of salicylic acid was higher at higher pHs, which was related to the increase in solubilities. Pellets were annealed at 20, 40, and 80 degrees C. A lower release rate was observed with increasing temperatures. Above the glass transition temperature (Tg) of the polymer, the release of drugs was significantly decreased. The drug release was independent of the ionic strength of the media for both salicylic acid and theophylline. We showed earlier that no drug-polymer interactions or polymer degradation were observed when studied by differentials scanning calorimetry (DSC) and infrared spectroscopy (IR) (1). The release mechanism was primarily physical diffusion and leaching during the experimental period. We conclude that the release of low molecular weight (MW) drugs from the high MW L-PLA was independent of the pH and the ionic strength of the dissolution media, but was dependent on the polarity of the drug and formulation factors, such as compression pressure and annealing temperature.
通过直接压片技术，在不使用加热或有机溶剂的情况下，成功制备了用于肠胃外或口服的聚（L-乳酸）（L-PLA）微丸。选择水杨酸和茶碱作为候选药物。微丸中的药物释放受压片压力影响。药物的Higuchi图显示出t1/2依赖性药物释放模式。这些药物从PLA微丸中的释放速率与其在溶出介质中的溶解度直接相关。在较低pH值（<7）下，发现水杨酸的释放比茶碱慢；然而，在较高pH值（>7）下，水杨酸的释放比茶碱快。水杨酸在较高pH值下的释放速率更高，这与溶解度的增加有关。微丸在20、40和80摄氏度下进行退火处理。随着温度升高，观察到释放速率降低。高于聚合物的玻璃化转变温度（Tg）时，药物释放显著减少。水杨酸和茶碱的药物释放均与介质的离子强度无关。我们之前通过差示扫描量热法（DSC）和红外光谱（IR）研究表明，未观察到药物-聚合物相互作用或聚合物降解（1）。在实验期间，释放机制主要是物理扩散和溶出。我们得出结论，高分子量L-PLA中低分子量（MW）药物的释放与溶出介质的pH值和离子强度无关，但取决于药物的极性和制剂因素，如压片压力和退火温度。
