Use of chitosan and chitosan malate as an excipient in wet granulation of three water soluble drugs

Abstract

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.