Tang Yu, Singh Jagdish
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, ND 58105, USA.
Int J Pharm. 2008 Jun 5;357(1-2):119-25. doi: 10.1016/j.ijpharm.2008.01.053. Epub 2008 Feb 6.
The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (p<0.05) faster degradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.
本研究的目的是开发一种基于聚（d，l-丙交酯-乙交酯）（PLGA）的可注射相敏原位凝胶形成给药系统，用于阿司匹林的控释，并表征药物/聚合物相互作用对阿司匹林体外释放和聚合物降解的影响。将阿司匹林溶解于1-甲基-2-吡咯烷酮中的PLGA溶液中。使用聚乙二醇400作为增塑剂以减少初始突释。将溶液制剂注入水性释放介质中以形成凝胶库。定期取出释放的样品，并通过高效液相色谱法测定阿司匹林含量。使用质子核磁共振和凝胶渗透色谱法评估阿司匹林对PLGA基质降解的影响。基于PLGA的原位凝胶形成制剂仅在7天内控制了阿司匹林的体外释放。PLGA基质残留物分析表明，与空白制剂相比，载有阿司匹林的制剂中的PLGA表现出显著更快（p<0.05）的降解。这些发现表明阿司匹林导致PLGA异常快速降解。文献中报道的任何其他药物均未发现PLGA如此快速的降解。
