Department of Novel Drug Delivery Systems, Iran Polymer and Petrochemical Institute, Tehran, Iran.
Curr Drug Deliv. 2022;19(1):157-166. doi: 10.2174/1567201818666210617102634.
Typically, in situ forming implants utilize Poly (lactide- co- glycolide) (PLGA) as carrier and N-methyl-2-pyrrolidone (NMP) as solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations.
The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia.
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 has been 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. Results revealed that using a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks.
The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP exhibited 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 has been predicted to be non-Fickian diffusion.
通常情况下，原位形成植入物采用聚（乳酸-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，开发不同的载体以经济和安全的方式控制和持续释放各种药物是至关重要的。
本研究旨在评估布比卡因盐酸盐从原位形成系统作为术后局部麻醉的体外释放情况。
我们使用醋酸丁酸蔗糖（SAIB）、PLGA 50:50 以及它们的混合物作为载体来比较释放行为。此外，还评估了 PLGA 分子量（RG 502H、RG 503H 和 RG 504H）、溶剂类型和溶剂浓度对药物释放曲线的影响。通过考察体外药物释放、流变性能、溶解度和 DSC 以及形态学特性来对制剂进行表征。此外，还应用了 Korsmeyer-Peppas 和 Weibull 模型对实验数据进行了分析。结果表明，与单独使用 SAIB 和 PLGA 相比，使用它们的混合物可以将布比卡因盐酸盐的释放时间从 3 天延长至 2 周。
DSC 结果表明混合物具有相容性，因为它只显示了一个单一的 Tg。与其他溶剂相比，NMP 制剂表现出更高的突释释放和最终释放，分别提高了 30%和 96%。从 12%增加到 32%的溶剂浓度显著提高了药物释放，这证实了形态学结果中更大的孔隙率。从 Korsmeyer-Peppas 模型预测，药物释放的机制是非菲克扩散。
