Dissolution Profiles of Poorly Soluble Drug Salts in Bicarbonate Buffer

Abstract

Purpose: The purpose of the present study was to investigate the effect of buffer species on the dissolution profiles of poorly soluble drug salts, focusing on bicarbonate buffer (BCB).

Methods: Pioglitazone HCl (PIO HCl) and dantrolene sodium (DNT Na) were used as model drugs. Non-sink dissolution tests were performed using phosphate buffer (PB) and BCB (pH 6.5, buffer capacity: 4.4 mM/pH, ionic strength: 0.14 M, with/ without bile micelles). The pH value of BCB was maintained using a floating lid that avoided the loss of CO₂. The particles collected at the early stage of dissolution (< 5 min) were analyzed by powder X-ray diffraction, polarized light microscopy, and scanning electron microscopy. A bulk-phase pH shift precipitation test was also performed.

Results: The dissolution of PIO HCl was slower in BCB than in PB, whereas that of DNT Na was faster in BCB than in PB. The same trend was observed in the presence of bile micelles. Free-form precipitation on the surface of salt particles was observed early in their dissolution in both BCB and PB. However, the surface textures in BCB and PB were different. The bulk-phase precipitation of PIO was little affected by buffer species, whereas that of DNT was affected, but oppositely to the dissolution profile.

Conclusion: The dissolution profiles of PIO HCl and DNT Na in BCB were markedly different from those in PB. Free-form precipitation on the particle surface, rather than in the bulk phase, was affected by buffer species in the dissolution test.

Keywords: bicarbonate; biorelevant; disolution; salt; supersaturation.