背景:通常,原位形成植入物利用聚(丙交酯-共-乙交酯)(PLGA)作为载体和N-甲基-2-吡咯烷酮(NMP)作为溶剂。然而,必须开发不同的载体,以经济和安全方面的受控和持续的方式释放各种药物。
目的:本研究旨在评估盐酸布比卡因在手术后局部麻醉从原位形成系统中的体外释放。
方法:我们使用蔗糖乙酸异丁酸酯(SAIB),PLGA50:50,以及它们的混合物作为载体以比较释放行为。此外,PLGA分子量的影响(RG502H,RG503H,和RG504H),溶剂类型,和溶剂浓度对药物释放曲线的评价。通过研究其体外药物释放来表征制剂,流变性能,溶解度,DSC,除了它们的形态特性。此外,将Korsmeyer-Peppas和Weibull模型应用于实验数据。结果表明,与单独使用它们相比,SAIB和PLGA的混合物可以将盐酸布比卡因的释放从3天延长至2周。
结果:DSC结果通过显示单个Tg证明了混合物的相容性。与其他溶剂相比,具有NMP的制剂具有更高的突释和最终释放,分别为30%和96%。分别。将溶剂浓度从12%增加到32%,药物释放显著增加,这证实了形态学结果中较大的孔隙率。从Korsmeyer-Peppas模型来看,预测药物释放机制是非Fickian扩散。
BACKGROUND: Typically, in situ forming implants utilize Poly (lactide-co-glycolide) (PLGA) as a carrier and N-methyl-2-pyrrolidone (NMP) as a solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations.
OBJECTIVE: The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia.
METHODS: We used Sucrose acetate isobutyrate (SAIB), PLGA 50:50, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile was evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. The results revealed that a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks.
RESULTS: The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP had a higher burst release and final release in comparison with other solvents by 30% and 96%, respectively. Increasing the solvent concentration from 12% to 32% raised the drug release significantly, which confirmed the larger porosity in the morphology results. From the Korsmeyer-Peppas model, the mechanism of drug release is predicted to be non-Fickian diffusion.