释放改性剂对聚己内酯-布洛芬贴片可打印性及释药性能的影响

Effect of Release Modifiers on Printability and Drug Release Properties of Poly (ε-caprolactone)-Ibuprofen Patch

以聚己内酯为药物载体材料、布洛芬为模型药物,以微晶纤维素、羟丙基甲基纤维素、乙基纤维素为释放改性剂,采用熔融沉积成型打印技术制备具有类石墨烯层间交错网络结构的经皮给药贴片。经力学性能、动态流变性能、红外分析、结晶性能、体外药物释放性能测试并结合释放动力学模型拟合,分析释放改性剂对聚己内酯基药物复合材料熔融沉积成型打印性能、聚己内酯-布洛芬经皮给药贴片药物释放性能的影响。结果表明:微晶纤维素的添加提高了聚己内酯-布洛芬线材的拉伸强度,而乙基纤维素、羟丙基甲基纤维素的添加均在不同程度上降低了线材的拉伸强度;3种释放改性剂均提高了聚己内酯-布洛芬熔体的复数黏度、储能模量,其中微晶纤维素的提高最为显著;红外分析表明释放改性剂与聚己内酯和布洛芬之间仅为物理混合,未发生化学反应;3种释放改性剂均降低了聚己内酯-布洛芬贴片的结晶度;与乙基纤维素、羟丙基甲基纤维素相比,微晶纤维素对熔融沉积成型打印的经皮给药贴片的累积释药率提高最为明显,120 h内累积释药率从62.3%提高到99.4%。

The transdermal drug delivery patches with graphene-like interlayer interlaced network structure were fabricated by fused deposition modeling printing technology using poly(ε-caprolactone)(PCL) as the drug carrier material, ibuprofen(IBP) as the model drug, microcrystalline cellulose(MCC), hydroxypropyl methyl cellulose(HPMC), and ethyl cellulose(EC) as release modifiers. The effects of release modifiers on the printing properties of polycaprolactone based drug composites by melt deposition molding and the drug release properties of PCL-IBP transdermal delivery patches were investigated by mechanical properties, dynamic rheological properties, infrared analysis, crystallization, in vitro drug release properties, and release kinetics model fitting. The results showed that the addition of microcrystalline cellulose increased the tensile strength of the PCL-IBP filaments, while the addition of ethyl cellulose and hydroxypropyl methyl cellulose reduced the tensile strength of the filaments. The dynamic rheological results showed that three release modifiers all increased the complex viscosity and storage modulus of the PCL-IBP melt, among which the degree of improvement of the microcrystalline cellulose was the most significant. Infrared analysis showed that the release modifiers were merely physically mixed with PCL and IBP, and no chemical reaction occurred. The three release modifiers all reduced the crystallinity of the PCL-IBP patches. Compared with ethyl cellulose and hydroxypropyl methyl cellulose, the effect of microcrystalline cellulose on the increase in the accumulative release rate of the transdermal drug delivery patches printed by fused deposition modeling was the most remarkable, and the accumulative drug release rate increased from 62.3% to 99.4% within 120 h.