Preparation and Evaluation of a Controlled-Release Formulation of Nifedipine Using Alginate Gel Beads

Abstract

Alginate gel beads containing nifedipine (NP) were prepared using a gelation of alginate with calcium cations. The dissolution and absorption of NP from alginate gel beads were evaluated as a controlled-release formulation of NP. The release of NP from alginate gel beads was affected by the composition of uronic acid in alginate, and by the NP content in alginate gel beads. NP absorption after oral administration to beagle dogs of alginate gel beads prepared by air-drying was significantly lower than that after the administration of NP powder alone, due to the limited release of NP from the alginate gel beads in the gastrointestinal tract. On the other hand, the alginate gel beads prepared by freeze-drying improved the absorption of NP because of the increasing disintegration of alginate gel beads with decreasing structural strength. However, this method had poor reproducibility, compared with air-dried alginate gel beads. The gel beads with added alginate propylene glycol ester (PGA) swelled and released calcium ions rapidly, even in water. This is because PGA gels weakly to the calcium cation. Consequently, it was observed that NP release from the PGA gel beads was highly accelerated compared to the release from alginate gel beads. The higher serum level of NP with large variance was obtained after the oral administration of the PGA gel beads. Gel beads consisting of a 1: 1 ratio of PGA to alginate had intermediate characteristics between the alginate and PGA gel beads in respect to NP release and absorption. Furthermore, the oral administration of the PGA-alginate gel beads was found to reproduce a good sustained-release profile of serum level of NP comparable to that of a commercial sustained-release NP tablet. These results suggest that the PGA-alginate gel beads are useful for a controlled-release formulation of NP. © 1993, The Pharmaceutical Society of Japan. All rights reserved.