A Nifedipine Coground Mixture with Sodium Deoxycholate. II. Dissolution Characteristics and Stability

Abstract

Nifedipine is a poorly water soluble drug that demonstrates low bioavailability. In a previous study, a coground mixture of nifedipine with sodium deoxycholate (DCNa), a bile salt, immediately produced colloidal particles when dispersed in water. In this study, the effect of the weight fraction of DCNa, grinding time, dissolution media, and storage conditions on colloidal particle formation in solution was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction. A laser diffraction particle size analyzer was used to determine the particle size distribution curve in water. The size of particles formed in solution decreased with an increase in the weight fraction of DCNa and grinding time. A nifedipine-DCNa (1 : 2 w/w) mixture coground for 30 min was used in the experiments. Colloidal particle formation from the coground mixture was also observed in dissolution media of water and a pH 6.8 buffer solution at 37°C. Most precipitates passed through a filter with a pore size of 0.8 μm, but the particle size distribution in water was different from that in the pH 6.8 buffer solution. DCNa exhibited not only micellar solubilization for drug crystals, but also a retarding effect on drug crystal growth in a supersaturated solution. The latter effect could serve to form colloidal particles in solution. When stored under 75% relative humidity at 40°C for 1 month, the amorphous coground mixture crystallized, and the particle size in water markedly increased. Therefore, the weight fraction of DCNa, grinding time, dissolution media, and humidity during storage influence the dissolution characteristics of nifedipine from a coground mixture.

Key Words:

• Coground mixture
• Colloidal particle
• Humidity
• Nifedipine
• Sodium deoxycholate