School of Science, University of Greenwich, Chatham, Kent, UK.
Drug Dev Ind Pharm. 2013 Feb;39(2):218-27. doi: 10.3109/03639045.2012.670642. Epub 2012 Mar 28.
The aim of this study was to investigate the efficiency of hydrophilic polymers to enhance the dissolution rate of poorly water-soluble active pharmaceutical ingredients (APIs) processed by hot-melt extrusion (HME). Indomethacin (INM) and famotidine (FMT) were selected as model active substances while polyvinyl caprolactam graft copolymer, soluplus (SOL) and vinylpyrrolidone-vinyl acetate copolymer grades, Kollidon VA64 (VA64) and Plasdone S630 (S630) were used as hydrophilic polymeric carriers. For the purpose of the study, drug-polymer binary blends at various ratios were processed by a Randcastle single screw extruder. The physicochemical properties and the morphology of the extrudates were evaluated through X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Increased drug loadings of up to 40% were achieved in the extruded formulations for both drugs. INM and FMT exhibited strong plasticization effects with increasing concentrations and were found to be molecularly dispersed within the polymer blends. The in vitro dissolution studies showed increased INM/FMT release rates for all formulations compared to that of pure APIs alone.
本研究旨在探讨亲水性聚合物对热熔挤出（HME）加工的水溶性差的活性药物成分（API）的溶解速率的提高效率。选择吲哚美辛（INM）和法莫替丁（FMT）作为模型活性物质，而聚乙烯己内酰胺接枝共聚物、共聚维酮（SOL）和乙烯基吡咯烷酮-乙酸乙烯酯共聚物等级、共聚维酮 VA64（VA64）和泊洛沙姆 S630（S630）则用作亲水性聚合物载体。为了进行这项研究，以各种比例将药物-聚合物二元混合物通过 Randcastle 单螺杆挤出机进行加工。通过 X 射线衍射（XRD）、差示扫描量热法（DSC）和扫描电子显微镜（SEM）评估了挤出物的物理化学性质和形态。对于两种药物，在挤出制剂中都可以达到高达 40%的药物负载。随着浓度的增加，INM 和 FMT 表现出强烈的塑化作用，并且在聚合物混合物中被发现是分子分散的。体外溶解研究表明，与单独的纯 API 相比，所有制剂的 INM/FMT 释放速率都有所提高。
