Evaluation of hot-melt extrusion technique in the preparation of HPC matrices for prolonged release

摘要

The aim of the work was to explore the potential of hot-melt extrusion (HME) for preparing hydroxypro-pyl cellulose (HPC)-based prolonged-release matrices intended for oral administration. For this purpose, compressed and extruded systems, either composed of polymer only or containing different amounts of a model drug (theophylline or ketoprofen), were compared. The overall morphological/physical changes of the systems following interaction with water indicated that the manufacturing process would not exert a major influence on the swelling behavior of the polymeric matrices. On the other hand, the release rate was generally higher from HME systems probably due to an increase of the drug dissolution rate, which is in agreement with the relevant DSC data (loss of drug cristallinity). However, the technological characteristics of the matrices and the maximum drug load were demonstrated to depend on the mode of interaction of the active ingredient with the molten polymer. In this respect, the formation of a composite material from ketoprofen and HPC, when mixed in specific ratios, was supposed to explain the differences observed between compressed and extruded systems in terms of morphological characteristics, hydra-tion/swelling and release. The obtained results support the possibility of exploiting the advantages offered by HME technique, above all the potential for continuous manufacturing, in the preparation of prolonged-release swellable matrices based on a cellulose derivative.