An investigation into the use of low quantities of functional additives to control drug release from hot melt extruded solid dispersions for poorly soluble drug delivery
An investigation into the use of low quantities of functional additives to control drug release from hot melt extruded solid dispersions for poorly soluble drug delivery
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DOI：
10.1016/j.ijpharm.2020.119172
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发表时间：
2020-04-15
影响因子：
5.8
通讯作者：
Qi, Sheng
中科院分区：
文献类型：
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作者：
Alqahtani, Fahad;Belton, Peter;Qi, Sheng
本研究的动机是证明在单步热熔挤出（HME）工艺中生产缓释和快速释放产品的实用性。HPMCAS作为载体材料在模型药物卡马西平（CBZ）的整体控释制剂中显示出良好的潜力。作为二元制剂，CBZ-HPMCAS挤出物在24小时内显示零级释放，这伴随着挤出物的溶胀。以低量使用一系列功能性赋形剂以调节释放速率。HME挤出物的释放速率可通过稀释少量（5%w/w）可溶性添加剂来加速或通过添加脂质赋形剂Gelucire 50/13来进一步维持。与二元挤出物相比，挤出物中的可溶性添加剂（包括交联羧甲基纤维素钠、羟基乙酸淀粉钠、麦芽糖糊精和乳糖）的清楚的相分离导致更高的内部孔隙率和更快的侵蚀。挤出物中的相分离Gelucire导致挤出物的显著溶胀并导致进一步延长的药物释放。本研究提供了明确的处方策略，用于调节由单步HME直接制备的控释制剂的药物释放速率。此外，这项研究工作还首次评估了HME挤出物同时溶胀和药物释放使用这种紫外成像技术。该仪器的整个剂量单元用于提供对由HME制备的固体分散体的溶解过程的了解。
The motivation of this study is to demonstrate the practicality of producing slow release and fast release products in a single-step hot melt extrusion (HME) process. HPMCAS as the carrier material showed good potential in monolithic controlled release formulations for the model drug, carbamazepine (CBZ). As binary formulations, CBZ-HPMCAS extrudates showed zero-order release over 24 h which was accompanied by the swelling of the extrudates. A range of functional excipients was used at low quantities to modulate the release rate. The release rates of the HME extrudates could be either accelerated by the incorporations of low quantities (5% w/w) of soluble additives or further sustained by adding lipid excipient, Gelucire 50/13. Clear phase separations of the soluble additives including crosscarmellose sodium, sodium starch glycolate, maltodextrin and lactose in the extrudates led to higher interior porosity and quicker erosion in comparison to the binary extrudates. The phase separated Gelucire in the extrudates led to the substantial swelling of the extrudates and resulted in further prolonged drug release. This study provided clear formulation strategies for modulating the drug release rate from controlled release formulation prepared directly by single-step HME. In addition, this research work also evaluates for the first time HME extrudates simultaneous swelling and drug release using this UV imaging technique. The whole dose cell of this instrumentation is utilised to provide insights into the dissolution process of solid dispersions prepared by HME.