CALCIUM ALGINATE MATRICES FOR ORAL MULTIPLE-UNIT ADMINISTRATION .4. RELEASE CHARACTERISTICS IN DIFFERENT MEDIA

The release properties of calcium alginate minimatrices were studied in media of various compositions. Three drugs with different aqueous solubility (paracetamol, theophylline and chloramphenicol) were incorporated as model substances and their release rates were investigated in 0.1 M HCl and water. The theophylline release was also studied in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), 0.034 M NaCl and 0.1 M NaCl. Additionally, the simultaneous liberation of calcium ions from the carrier material into the different media was analysed and illustrated by means of calcium release curves. Only when pure water was applied as release medium were the matrices able to extend the release of the two least soluble model drugs, theophylline and chloramphenicol. In all other media the drug release proceeded much more rapidly, due to various transformations in the carrier material. The cross-linking calcium ions were rapidly discharged from the matrices in the presence of acid, and the carrier material was converted to alginic acid. Although the transformation did not change the morphology or the swelling behaviour of the matrices, it destroyed their ability to provide retarded drug release. In the NaCl solutions and SIF, the calcium ions were partly exchanged by the non-gelling sodium ions or sequestered by the phosphate. This caused swelling and, in the latter case, dissolution of the matrices, and induced a rapid release of the encapsulated drug. Due to the pronounced sensitivity towards the composition of the release medium and the rapid drug release in media of physiological relevance, it was concluded that the minimatrices do not seem applicable as an oral controlled release system.