Effect of Additives on the Physicochemical and Drug Release Properties of Pioglitazone Hydrochloride Spherical Agglomerates

Purpose: To prepare and evaluate spherical agglomerates of pioglitazone hydrochloride (PGH) for direct compression with different additives. Method: Spherical agglomerates of pioglitazone hydrochloride were prepared by emulsion solvent diffusion method with and without additives (polyethylene glycol 6000, polyvinyl pyrrolidone, beta cyclodextrin, Eudragit RS100, low acyl gellan gum and xanthan gum) using methanol, chloroform and water as good solvent, bridging liquid and poor solvent respectively. The agglomerates were evaluated for compressibility, solubility and dissolution rate and also by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and fourier transforms infrared spectroscopy (FTIR). Results: The particle size, flowability, compactibility, packability, solubility and dissolution rate of plain agglomerates and agglomerates with additives, except polyvinyl pyrrolidone, were enhanced compared with the original crystals of pioglitazone hydrochloride. This might be attributed to their large size (10 x original PGH crystals), spherical shape, enhanced fragmentation during compaction (yield pressure increased from 22.6 to 29.3 MPa) and reduced elastic recovery of compacts (from 8.1 to 5.5 %) compared to the original drug crystals. XRPD and DSC studies indicate polymorphic transition of PGH in all agglomerates from form II to I during recrystallization; FTIR spectra show that this was not associated with any chemical transition. Conclusion: The findings indicate that spherical crystallization by emulsion solvent diffusion method to produce agglomerates containing selected additives is a satisfactory approach for the formulation of directly compressed pioglitazone hydrochloride tablets.