Compression of Indomethacin Coprecipitates with Polymer Mixtures: Effect of Preparation Methodology

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Abstract
The objective of this study was to prepare, characterize, formulate and compare coprecipitates, solid dispersions and physical mixtures of indomethacin with Eudragit polymer mixtures, RS100 and L100. Coprecipitates, solid dispersions (melting-solvent method) and physical mixtures were prepared with a drug : polymer ratio of 12.6: 1.0 respectively. Biconvex tablets of 7 mm diameter were compressed. Response variables studied were cumulative percent released and T50. Dissolution was performed by exposing the tablets to SGF (PH 1.2) for 1 hour followed by pH 7.2 phosphate buffer for 24 hours. T50 values obtained were 7.5 hours for coprecipitates, 4.5 hours for solid dispersions and 17 hours for physical mixtures. The drug loading for all the three formulations did not show significant difference. The formulations were characterized by X-ray diffraction (qualitative and quantitative) and IR. IR data did not indicate any significant difference between the pure drug and the formulations. However, significant differences were seen in X-ray diffractograms. The crystallinity did not change for physical mixtures, was reduced for coprecipitates and solid dispersions. Also the diffraction patterns for solid dispersions and coprecipitates were similar. The coprecipitates and physical mixture followed the Higuchi's square-root-of-time equation suggesting a matrix effect. These results suggest that compression of coprecipitates offer most efficient release as compared to solid dispersions and physical mixtures.