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.