Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion

The objective of the study was to prepare solid dispersions containinga thermallly unstable drug by hot-melt extrusion (I-TME). Carbarnitzepine (CBZ) was selected as model drug and combinations of Kollidon VA64 (VA64), Soluplus (SOL) and Eudragit EPO (EPO) were utilized as carriers. Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters, differential scanning calorimetry (DSC), hot stage microscopy and thennogravimetric analysis. Physicochemical properties of solid dispersions were determined by DSC, X-ray diffraction, founer transform infrared spectroscopy, dissolution and accelerated stability testing. The results show that drug-polymer miscibility at temperatures below the melting point (T-m) of C:BZ was improved by combining EPO with VA64 or SOL. With 30% drug loading in a solid dispersion in SOL:EPO (1:1, CBZ was mainly present in an amorphous fonn accompanied by a small amount of a rnicfrociystalline form. The dissolution rate of the solid dispersion was significantly increased (approximately 90% within 5 ruin) compared to either the pure drug (approximately 85% within 60 min) or the corresponding physical mixture (approximately 80% within 60 min) before and after storage. The solid dispersion in SOL:EPO CI:I, (OD was relatively stable at 40 degrees C/75% RH under CBZ tablet packaging conditions for at least 3 months. In conclusion, polymer combinations that impmve drug-polymer miscibility at an HME processing temperature below the Ta, of a dmg appear to be beneficial in the preparation of solid dispersions containing then-nally unstable drugs. (C) 2013 Institute ledica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association. Production and hosting by Elsevier B.V. All rights reserved.