Effect of formulation variables on in vitro release of a water-soluble drug from chitosanesodium alginate matrix tablets

The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets.

Critical points in the formulation of pharmaceutical swellable controlled release dosage forms——Influence of particle size

Swellable matrix represents one of the most employed controlled release systems. These dosage forms provide slow release of drugs to reduce the fluctuation of drug concentration in plasma in order to improve the efficiency of treatment and/or to reduce adverse effects. The application of the concepts of statistical physics has allowed discovering the existence of critical points in the formulation of swellable matrices. These points, representing the volume fractions of the tablet components where the properties of the matrix diverge or change suddenly, provide important knowledge of how to rationalize the design of swellable matrices. The critical points are generally related to the percolation threshold of one of the components of the formulation, which corresponds to a geometrical phase transition of this component, passing from isolation to spanning the whole system. The last section of the paper is devoted to more recent findings concerning the influence of particle size of the components on the percolation threshold of the matrix forming polymer, and therefore on the release behaviour of the matrix. Knowledge of the excipient percolation threshold allows a more rational design of swellable matrices, according to the guidelines of the regulatory authorities concerning science-based formulation and quality by design.