Application of mixtures of polymeric carriers for dissolution enhancement of oxeglitazar using hot-melt extrusion

摘要

Hot-melt extrusion was applied to improve the solubility of the poorly water-soluble drug oxeglitazar. Various polymers and their blends were used as carriers: copovidone (COP), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (PVCL-PVAc-PEG) and hypromellose 2910/5 (HPMC). After extrusion, the extrudate was pelletized. The physical state of the drug was assessed using X-ray diffraction and differential scanning calorimetry. The dissolution performance of the extrudates was compared to the physical mixture and pure oxeglitazar. The stability under long-term storage conditions (25°C/60%rH) was investigated.The solubility of oxeglitazar was improved with all hot-melt extruded formulations: 26-66% of the drug was dissolved and a 1.9-5.0-fold supersaturation was reached with the pelletized extrudates. All extrudates which were assessed for their storage stability showed sufficient product stability. A super-additive effect of COP and HPMC as a polymeric blend was successfully demonstrated as a higher supersaturation and longer time of supersaturation were shown for the ternary blend. Through variations of the ratio COP:HPMC, it was shown that the shape of the dissolution curve is dominated by the polymer with the higher amount in the polymeric blend. If PVCL-PVAc-PEG is applied as single or additional carrier, the initial release rate is drastically reduced.