Calcium alginate matrices for oral multiple unit administration: III. Influence of calcium concentration, amount of drug added and alginate characteristics on drug release

Abstract

The influence of the calcium concentration, the amount of drug added and the characteristics of the alginate on the encapsulation and release of theophylline from minimatrices made of calcium alginate were studied. The combined effects of the calcium concentration used for gelation and the amount of drug added during matrix production was investigated by means of a central composite design. Both factors influenced the drug encapsulation and drug release rate in water. The response surfaces for the release parameters t 50% and T d showed that the slowest release was obtained from matrices prepared using intermediate levels of the two factors. The retardation was, however, relatively small, and t 50% and T d did not exceed 1.5 and 2.8 h, respectively. Drug release in 0.1 M HCl was very rapid from all the formulations tested. It was only slightly affected by the amount of drug added during matrix production and was not influenced by the calcium concentration. A high G alginate was used as carrier material in the matrices investigated during the central composite design. Alginates containing fewer G residues gave matrices with a lower encapsulation efficiency and a faster drug release rate in both dissolution media. An increase in the mean molecular weight of the alginate from 200 000 to 270 000 did not affect the release properties.