College of Pharmaceutical Sciences, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310032, People's Republic of China.
Ocean College, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310032, People's Republic of China.
AAPS PharmSciTech. 2019 Jun 14;20(6):219. doi: 10.1208/s12249-019-1435-7.
Hydroxypropyl methylcellulose (HPMC) is a hydrophilic retarding-release polymer with the limited application in hot melt extrusion (HME) due to its high glass transition temperature (T 181-191°C) and melt viscosity. The aim of this study is to develop hot melt extruded matrices using hydroxypropyl cellulose (HPC) and felodipine (FLDP) with HPMC for controlled release and explore the relations of their specialty, processability, and structure with the product properties. Results showed that FLDP/HPC/HPMC can be extruded at 160°C with torques not more than 0.5 N·m. The extruded matrices of FLDP/HPC/HPMC (10:45:45 and 30:35:35) achieved the controlled release for 24 h. Rheological behaviors demonstrated that HPC and FLDP were miscible with HPMC, attaining maximum 30% FLDP soluble in the molten mixtures. HPC and FLDP decreased the complex viscosity and plasticized HPMC to improve the extrusion processing. DSC and FT-IR indicated that the molten soluble FLDP was amorphous in the extruded matrices by hydrogen bonding with HPC/HPMC. SEM/energy-dispersive X-ray microanalysis illustrated that the microstructure of extrudates was surface dense and interior loose, and FLDP was homogenously dispersed. Three-point bending test revealed that the plasticizers of HPC and FLDP contributed differently to the mechanical properties. HPC decreased the flexural modulus of HPMC while that of HPC/HPMC was increased by FLDP. Besides controlled release, low moisture absorption and enhanced stability were also the correlated achievements. Therefore, HPC-combined poorly water-soluble drugs to plasticize HPMC provide an alternative novel potential approach to realize the controlled-release delivery via HME.
羟丙基甲基纤维素（HPMC）是一种亲水性延迟释放聚合物，由于其玻璃化转变温度（T 181-191°C）和熔体粘度较高，因此在热熔挤出（HME）中的应用有限。本研究旨在开发使用羟丙基纤维素（HPC）和非洛地平（FLDP）与 HPMC 的热熔挤出基质，以实现控制释放，并探索它们的特性、加工性能和结构与产品性能的关系。结果表明，FLDP/HPC/HPMC 可以在 160°C 下挤出，扭矩不超过 0.5 N·m。FLDP/HPC/HPMC（10:45:45 和 30:35:35）的挤出基质实现了 24 小时的控制释放。流变行为表明，HPC 和 FLDP 与 HPMC 混溶，可使熔融混合物中最大 30%的 FLDP 溶解。HPC 和 FLDP 降低了复合粘度并塑化了 HPMC，从而改善了挤出加工性能。DSC 和 FT-IR 表明，熔融可溶的 FLDP 通过与 HPC/HPMC 形成氢键在挤出基质中呈无定形状态。SEM/能谱微分析表明，挤出物的微观结构为表面致密、内部疏松，FLDP 均匀分散。三点弯曲试验表明，HPC 和 FLDP 的增塑剂对机械性能的贡献不同。HPC 降低了 HPMC 的弯曲模量，而 HPC/HPMC 的弯曲模量则因 FLDP 的加入而增加。除了控制释放外，低吸湿性和增强的稳定性也是相关的成果。因此，将 HPC 与难溶性药物结合以塑化 HPMC，为通过 HME 实现控制释放输送提供了一种替代的新方法。
