Application of solid dispersions of nifedipine with enteric coating agent to prepare a sustained-release dosage form.

Abstract

Pre-formulation studies were carried out to develop a sustained-release dosage form of nifedipine with good bioavailability. Granules were prepared by spray-coating nifedipine-enteric coating agent solid dispersions on an inert core material. Typical enteric coating agents, hydroxypropylmethylcellulose phthalate and methacrylic acid-methacrylic acid methyl ester copolymer, were used as carriers of the solid dispersions. Dissolution of nifedipine from granules coated with solid dispersions was practically nil in JPX 1st fluid, but a supersaturation phenomenon was observed in JPX 2nd fluid. These granules resulted in prolonged absorption of the drug with good bioavailability in beagle dogs and human volunteers. This absorption characteristic arises from the pH dependency of the dissolution behavior of these solid dispersions. That is, dissolution of nifedipine was suppressed in acidic medium and showed supersaturation in comparatively neutral medium. It was confirmed that the granules were transported through the gastrointestinal tract and showed prolonged drug release behavior with good bioavailability.