Coffin M D, McGinity J W
Glaxo Inc., Research Triangle Park, North Carolina 27709.
Pharm Res. 1992 Feb;9(2):200-5. doi: 10.1023/a:1018981222092.
Pseudolatexes of the biodegradable polyesters poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL) have been developed as potential aqueous coatings for sustained release. Since PLA and PCL are known to hydrolyze, the influence of the surfactant system, temperature, pH, and particle size on the chemical stability of the polymers as aqueous colloidal dispersions was investigated. Pseudolatexes of PLA and PCL formulated with a nonionic surfactant system were the most stable. When these dispersions were stored in unbuffered media for 350 days at 5 degrees C, only small changes in the weight-average molecular weights (Mw) of the polymers were observed. At 37 degrees C there was rapid degradation of both polymers in the dispersions. Arrhenius plots for the degradation of PLA and PCL resulted in a linear relationship for PCL. The nonlinear relationship for PLA was attributed to the polymer being in two different physical states within the 5 to 37 degrees C range which was used for the Arrhenius plots. PCL was in the rubbery state at all temperatures studied. Storage of the pseudolatexes in pH 1.65 buffer at 37 degrees C catalyzed the rates of degradation of both PLA and PCL. However, refrigeration of the pseudolatexes stabilized the polymers even at pH 1.65 for up to 4 months. Particle size had an insignificant effect on PLA and PCL stability in pseudolatexes prepared with either a nonionic or an anionic surfactant system.
可生物降解聚酯聚(D,L-丙交酯)(PLA)和聚(ε-己内酯)(PCL)的假胶乳已被开发为用于缓释的潜在水性包衣。由于已知PLA和PCL会水解,因此研究了表面活性剂体系、温度、pH值和粒径对聚合物作为水性胶体分散体的化学稳定性的影响。用非离子表面活性剂体系配制的PLA和PCL假胶乳最稳定。当这些分散体在5℃的无缓冲介质中储存350天时,仅观察到聚合物的重均分子量(Mw)有微小变化。在37℃时,分散体中的两种聚合物都迅速降解。PLA和PCL降解的阿仑尼乌斯图显示PCL呈线性关系。PLA的非线性关系归因于该聚合物在用于阿仑尼乌斯图的5至37℃范围内处于两种不同的物理状态。在所有研究温度下,PCL均处于橡胶态。将假胶乳储存在37℃的pH 1.65缓冲液中会催化PLA和PCL的降解速率。然而,即使在pH 1.65下,将假胶乳冷藏也能使聚合物稳定长达4个月。在使用非离子或阴离子表面活性剂体系制备的假胶乳中,粒径对PLA和PCL的稳定性影响不大。