Jalil R, Nixon J R
Chelsea Department of Pharmacy, King's College London, University of London.
J Microencapsul. 1990 Jul-Sep;7(3):357-74. doi: 10.3109/02652049009021846.
Poly(DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (PB) were prepared using a w/o emulsion-evaporation method. DL-PLA of three different molecular weights, 20,200, 13,300 and 5,200 were used to prepare microcapsules of nominal core: polymer (C:P) ratios of 1 : 2, 1 : 2.5, 1 : 3 and 1 : 4. The release of PB was investigated in aqueous buffer of pH 2, pH 7 and pH 9 at 37 degrees C and found to follow a square root of time dependent release mechanism. The first order and zero order release mechanisms were disproved by the lower correlation coefficient of the release data as compared to that of the t1/2 mechanism. These microcapsules showed an initial burst phase release followed by a lag phase, during which time little PB was released. This lag time was affected by the polymer molecular weight and pH of the buffer. The polymer matrix was hydrated during the lag phase and a steady state release occurred. The steady state release rate per unit specific surface area (Kh2/SSA) was found to increase exponentially with the increase in core loading of the microcapsules. However the extent of normalized release rate reduced linearly with the increase in polymer molecular weight at any particular core loading (e.g. 20 per cent or 30 per cent). Increases in the normalized steady state release rate with an increase in buffer pH could be correlated to PB solubility in the dissolution medium. PB release from these microcapsules was diffusion controlled. However, swelling and erosion also contributed to the release process.
采用油包水乳液蒸发法制备了含苯巴比妥（PB）的聚（DL-乳酸）[DL-PLA]微胶囊。使用三种不同分子量（20,200、13,300和5,200）的DL-PLA制备标称芯材与聚合物（C:P）比例为1:2、1:2.5、1:3和1:4的微胶囊。在37℃下，于pH 2、pH 7和pH 9的水性缓冲液中研究了PB的释放情况，发现其遵循与时间平方根相关的释放机制。与t1/2机制相比，释放数据的较低相关系数证明一级和零级释放机制不成立。这些微胶囊表现出初始突释阶段，随后是一个滞后阶段，在此期间几乎没有PB释放。该滞后时间受聚合物分子量和缓冲液pH值的影响。在滞后阶段聚合物基质发生水合作用，并出现稳态释放。发现单位比表面积的稳态释放速率（Kh2/SSA）随微胶囊芯材负载量的增加呈指数增加。然而，在任何特定的芯材负载量（例如20%或30%）下，归一化释放速率的程度随聚合物分子量的增加呈线性降低。归一化稳态释放速率随缓冲液pH值的增加而增加，这与PB在溶解介质中的溶解度相关。PB从这些微胶囊中的释放是扩散控制的。然而，溶胀和侵蚀也对释放过程有贡献。
