Development and Evaluation of Implant using Hot-Melt Extrusion

S. Lee, Geunjeong Lee, Young Jin Kim, Young ho Cho, Gye-Won Lee
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Abstract

In this study, poly(lactic-co-glycolic acid) (PLGA)-based subcutaneous implant containing metformin HCl was prepared by hot-melt extrusion (HME). This study aimed to evaluate swelling and dissolution behavior for application as subcutaneous implant. Implants containing metformin HCl were fabricated successfully at 30 rpm, 90oC by HME. Drugexcipient compatibility studies through FT-IR and DSC revealed the absence of any interaction between the drug and polymers. Dissolution rate and swelling ratio of metformin HCl was significantly affected by the type of PLGA. Dissolution rate increased as the ratio of -COOH terminal group and GA. By the results, we could confirm that the mechanism of drug release from implants is Korsmeyer-Peppas model (n=0.14~0.71) by combination of non-fickian diffusion and erosion. The formulation F7 with 65% of RG 752H and 5% of RG 502 was showed excellent swelling ratio with drug release control. In this study, mixing 5~10% of RG 502 with RG 752H can be expected to develop optimal implants exhibiting diffusion-controlled release for 3 months without initial burst release.
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热熔挤压种植体的研制与评价
本研究采用热熔挤压(HME)法制备了含二甲双胍的聚乳酸-羟基乙酸(PLGA)皮下植入物。本研究旨在评估其作为皮下植入物的溶胀和溶解行为。含二甲双胍HCl的植入物在30 rpm, 90℃的HME下成功制备。通过FT-IR和DSC进行的药物赋形剂相容性研究显示药物和聚合物之间没有任何相互作用。PLGA类型对盐酸二甲双胍溶出率和溶胀率有显著影响。溶解速率随-COOH末端基团与GA的比值增大而增大。结果表明,种植体的药物释放机制为Korsmeyer-Peppas模型(n=0.14~0.71),为非黏性扩散和侵蚀相结合的释放机制。F7中RG 752H含量为65%,RG 502含量为5%,具有良好的溶胀率和控释效果。在本研究中,将5~10%的RG 502与RG 752H混合,有望开发出最佳的植入物,具有3个月的扩散控制释放,没有初始爆裂释放。
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