Effect of buffer capacity on dissolution and supersaturation profiles of pioglitazone hydrochloride

Abstract

The purpose of the present study was to investigate the effect of buffer capacity (β) on the dissolution, supersaturation, and precipitation (DSP) profiles of a salt form drug. The DSP of pioglitazone HCl (PIO–HCl, pKa = 5.8, intrinsic solubility = 0.4 μg/mL) was investigated under a non-sink condition (30 mg in 500 mL) in phosphate and maleate buffers with various β (2–32 mM/ΔpH) at pH 6.5. Precipitation from the bulk solution was investigated by a pH-shift method (pH 3.0 to 6.5). The slurry pH was measured to assess the solid surface pH. As β was increased, the degree of supersaturation in the non-sink dissolution test decreased from 25 to less than 3. The PIO-HCl particles transformed to the free base (PIO-FB) while retaining the outer shape of the initial particles. In the pH-shift precipitation test, β did not affect the precipitation of PIO-FB, and the shape of precipitant was different from that in the dissolution tests. The pH of the PIO-HCl slurry increased from 0.9 to 1.6 as β increased. In conclusion, buffer capacity had a marked impact on the PIO-HCl DSP profile. PIO-HCl transformed to PIO-FB before dissolving into the bulk phase.