Influence of Sodium Caseinate on the Dissolution Rate of Hydrochlorothiazide and Chlorothiazide

Abstract

The solubility and dissolution characteristics of drug-casein systems were investigated and their solid state properties examined. Systems of varying drug-sodium caseinate weight fraction were prepared by physical mixing and freeze drying. Enhancements in the intrinsic dissolution rates were obtained for freeze dried systems of both drugs. The relative enhancement for 50/50 systems in phosphate buffer pH 7.4 was 5 fold and 1.5 fold for chlorothiazide and hydrochlorothiazide respectively. A 35 fold increase was observed for the chlorothiazide system in water, The release of both drugs from mechanically mixed systems in phosphate buffer approximated to a non interacting model, while release from hydrochlorothiazide systems in 0.1N HC1 showed a tendency towards matrix controlled release. Thus the magnitude of the effect is dependant on the nature of the drug, the content of carrier, the method of preparation and the dissolution medium.