USE OF CHITOSAN AND CHITOSAN MALATE AS AN EXCIPIENT IN WET GRANULATION OF 3 WATER-SOLUBLE DRUGS

The drug release from granules containing two different chitosan qualities was studied, using three model drugs. Granules were prepared by standard wet granulation, starting with a dry blend of drug and chitosan followed by spraying with a granulating fluid. The resulting granules have good flow properties, except from formulations with the cationic model drug (chloroquine), which gave electrical charged granules. Theophylline granules containing from 25 to 75% of chitosan malate showed an increasing sustained release effect when the chitosan malate content was increased. Zero-order kinetics for the dissolution rate was observed for all three drugs in formulations with a content of 75% chitosan malate. This was probably due to the swelling of the granules in acidic solution. In contrast to the formulations containing chitosan malate as an excipient, theophylline granules containing 25-90% chitosan (SeaCure 452) showed more rapid dissolution than the pure drug, due to fast disintegration and a wetting effect. In dissolution medium no. 2 (pH 6.8), the swelling was less marked, but an interaction between the phosphate buffer and chitosan malate appeared to influence the drug release rate.