Marcotte N, Polk A, Goosen M F
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
J Pharm Sci. 1990 May;79(5):407-10. doi: 10.1002/jps.2600790509.
The release kinetics of albumin diffusion from a poly(D,L-lactide) reservoir system was investigated with the long-term aim of developing a multidose pulsatile delivery system. Albumin pellets were coated with polylactide of varying viscosity-average molecular weight, Mv, and concentration, and incubated in aqueous solution. The albumin release profile was approximated by zero-order release kinetics, with release rates ranging from 3 to 1800 mg/day. The permeability of the poly(D,L-lactide) membranes to albumin diffusion ranged from 1 x 10(-9) to 100 x 10(-9) cm2/S, and was found to decrease with increasing membrane thickness (18 to 1400 microns) and density (300 to 3000 mg/cm3). The initiation of albumin release from the pellets could be delayed from a few hours to more than one month by increasing the Mv of the polylactide from 6.2 x 10(3) to 140 x 10(3) and raising the concentration of the polymer coating solution from 50 to 100 mg/mL. The diversity in delayed-release effect and the variations in membrane permeabilities were attributed to changes in membrane porosity and polymer morphology.
为了开发一种多剂量脉冲给药系统，对聚（D，L-丙交酯）储库系统中白蛋白扩散的释放动力学进行了研究。用不同粘均分子量（Mv）和浓度的聚丙交酯包被白蛋白微丸，并在水溶液中孵育。白蛋白释放曲线可用零级释放动力学近似，释放速率范围为3至1800毫克/天。聚（D，L-丙交酯）膜对白蛋白扩散的渗透率范围为1×10⁻⁹至100×10⁻⁹平方厘米/秒，并且发现随着膜厚度（18至1400微米）和密度（300至3000毫克/立方厘米）的增加而降低。通过将聚丙交酯的Mv从6.2×10³提高到140×10³，并将聚合物包衣溶液的浓度从50毫克/毫升提高到100毫克/毫升，白蛋白从微丸中的释放起始时间可以从几小时延迟到一个多月。延迟释放效果的多样性和膜渗透率的变化归因于膜孔隙率和聚合物形态的变化。
