Claeys Bart, Vervaeck Anouk, Hillewaere Xander K D, Possemiers Sam, Hansen Laurent, De Beer Thomas, Remon Jean Paul, Vervaet Chris
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
Polymer Chemistry Research Group, Department of Organic Chemistry, Ghent University, Ghent, Belgium.
Eur J Pharm Biopharm. 2015 Feb;90:44-52. doi: 10.1016/j.ejpb.2014.11.003. Epub 2014 Nov 15.
This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM.
本研究评估了热塑性聚氨酯（TPUR）作为基质辅料，通过热熔挤出（HME）结合注塑成型（IM）来生产口服固体剂型。我们证明，TPUR能够在低于药物熔点（Tm）的挤出温度下生产固体分散体——结晶载体中的结晶活性药物成分（API），药物含量高达65%（重量）。酒石酸美托洛尔的释放可控制24小时，而二羟丙茶碱只有与药物释放调节剂聚乙二醇4000（PEG 4000）或吐温80联合使用时才能完全释放。溶出度测试后，任何制剂均未检测到突释现象，片剂尺寸和几何形状也未发生变化。药物释放时，总基质孔隙率逐渐增加。通过人体肠道微生物生态系统模拟器（SHIME）监测发现，口服TPUR不会影响胃肠道生态系统（pH值、细菌计数、短链脂肪酸）。在通过HME/IM生产的制剂领域，制剂的高载药量（65重量%）以及（体外和体内）控释能力值得关注。
