Dissolution Profiles of Poorly Soluble Drug Salts in Bicarbonate Buffer.

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.

Dissolution Kinetics of Nifedipine-Ionizable Polymer Amorphous Solid Dispersion: Comparison Between Bicarbonate and Phosphate Buffers.

PURPOSE: The intestinal fluid pH is maintained by the bicarbonate buffer system that shows unique properties regarding drug dissolution. Nevertheless, current compendial dissolution tests use phosphate buffers. The purpose of the present study was to investigate the effect of bicarbonate and phosphate buffers on the dissolution profiles of amorphous solid dispersions (ASD) composed of ionizable polymers. METHODS: Hydroxypropylmethylcellulose acetate succinate (HPMCAS), amino methacrylate copolymer (AMC), and hydroxypropylmethylcellulose (HPMC) were employed as acidic, basic, and neutral polymers, respectively. Nifedipine (NIF) was used as a model drug. Dissolution profiles were measured in pH 6.5 bicarbonate and phosphate buffers by a mini-scale paddle dissolution test. The pH of bicarbonate buffers was maintained by the floating lid method. RESULTS: The pH change of the bicarbonate buffer was suppressed to less than + 0.25 pH for 3 h by the floating lid method. In all cases, the NIF concentration was supersaturated against the solubility of crystalline NIF. The dissolution rates of HPMCAS and AMC ASDs were 1.5 to 2.0-fold slower in the bicarbonate buffer than in the phosphate buffer when compared at the same buffer capacity. The dissolution profile of HPMC ASD was not affected by the buffer species. The higher the buffer capacity and ionic strength, the faster the dissolution rate of HPMCAS ASD. CONCLUSION: The dissolution rate of ASDs with ionizable polymers would be overestimated by using unphysiological phosphate buffer solutions. It is important to use a biorelevant bicarbonate buffer solution for dissolution testing.