Miyajima M, Koshika A, Okada J, Ikeda M
Product Development Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
J Control Release. 1999 Aug 5;60(2-3):199-209. doi: 10.1016/s0168-3659(99)00083-8.
The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium.
研究了酸性和中性药物从聚（L-乳酸）[P（L）LA]基质中的释放曲线，以揭示其释放机制。通过热压法制备圆柱形基质（棒；直径10mm×1mm）。将所研究的酸性和中性药物溶解在P（L）LA棒中。发现释放曲线由两个连续阶段组成。在第一个释放阶段，P（L）LA保持无定形状态，药物通过水合基质扩散。在第二个释放阶段，P（L）LA转变为半结晶状态，药物通过聚合物结晶形成的充满水的微孔扩散。此外，还发现药物在棒中以晶体形式沉淀出来，导致棒转变为药物分散基质。基于这些发现，我们推导了第二个阶段药物释放的修正扩散方程。该方程与这些药物的释放曲线拟合良好。此外，棒中药物含量的降低和介质pH值的升高均导致药物释放分数速率加快，这支持了所推导方程的有效性。
