EVALUATION OF MISCIBILITY BETWEEN MODEL DRUG AND POLYMER IN HOT MELT EXTRUDED FILMS

Abstract

The aim of this study was to investigate miscibility between model drugs and polymer in the extruded films prepared by hot melt extrusion. The model drugs with different crystallization tendency were benzocaine (BZC), indomethacin (IND) and paracetamol (PAR) and the polymer was semi-crystalline polylactide. Drug-polymer miscibility was predicted by calculation and their thermal properties. The miscibility between drug and polymer in extrudates was evaluated by X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC). Drug-polymer interaction was also investigated by Fourier transform infrared spectroscopy (FTIR). Prediction by calculating solubility parameters suggested that BZC and IND were miscible, while PAR was immiscible with polylactide. This corresponded to thermal behaviors of the drug-polymer blends. The prediction results of IND and PAR agreed with drug-polymer miscibility in the extrudate, while BZC degraded at the extrusion process temperature. IND and PAR was miscible with polylactide up to the drug to polymer ratio of 50:50 and 10:90, respectively. Hydrogen bonding was mainly responsible for drug-polymer interaction in the miscible extrudate. The study revealed that the drug-polymer interaction was dependent on the drug content, being stronger than drug-drug interaction at the relatively low drug content. However, a plasticizing effect of the drugs in the extrudates was not observed.