Soluplus~R: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation

摘要

The aim of this work was to investigate the applicability of different industrially scalable techniques in the preparation of solid dispersions using a novel polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus~R) for preparing immediate-release formulations of a poorly water-soluble BCS class II drug. Carvedilol (CAR), a non-selective β-blocker, has been selected as poorly water-soluble model drug. The solid dispersions were prepared by three different techniques; solvent evaporation, freeze drying and spray drying in different CAR:Soluplus~R ratios using 3~2 full factorial design. Among the formulations tested, CAR solid dispersion preparation using freeze drying method at ratio of 1:10 (CAR: Soluplus~R) showed the highest saturation solubility and was selected for further investigation. Solid state characterization was evaluated by differential scanning calorimetry (DSC) and X-ray diffraction study (XRD), scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FTIR). DSC and XRD analyses indicated the complete transformation of CAR in the solid dispersion from crystalline to amorphous state. Selected CAR solid dispersion was further incorporated into ODTs using three commercially mannitol-based fillers; Pearlitol Flash~R, Pharmaburst~R and Ludifalsh~R. The ODTs were evaluated for hardness, disintegration time and drug dissolution. Pearlitol Flash~R, and Pharmaburst~R ODTs showed shorter disintegration times (<1 min) and significantly higher dissolution profile (>90% within 30 min) compared to Ludifalsh~R ODTs. Thus, the development of CAR solid dispersions using Soluplus~R as ODTs could be used as a promising approach for improving the solubility and oral bioavailability of poorly water-soluble drugs.