Solubility and Bioavailability Enhancement of Mosapride Citrate

Abstract

MC is a class II water-insoluble drug and its dissolution rate and, consequently, absorption are dependent on the gastrointestinal pH. This results in a very high variability in bioavailability and related inter- and intra-subject absorption variations which present a major challenge that hinders the realization of an effective and uniform therapy. Our aim of work in this thesis was to produce MC in a solid dosage form that can increase its aqueous solubility and as a result improves its oral bioavailability. Achieving this goal will enable us to reduce the administered dose, which is advantageous, taking into consideration the adverse effects of the drug and the cost-treatment relationship. To achieve these goals, the work in this thesis was divided into three chapters: Chapter I: Preparation of msoapride citrate tablets using liquisolid technique. Chapter II: Preparation of msoapride citrate tablets using complexation technique. Chapter III: Bioavailability and pharmacokinetic study of mosapride citrate tablets in healthy human volunteers. In chapter I, it was hypothesized that the formulation of MC using liquisolid compacts technique may reduce the effect of pH variation on the drug dissolution rate. Solubilities of MC in propylene glycol, PEG Summary 217 400, and glycerol formal were first measured and glycerol formal was selected due to its superiority in dissolving MC among the tested solvents. Several liquisolid tablet formulations containing various ratios of drug: glycerol formal (5% and 10% w/w) were prepared. The carriers used were microcrystalline cellulose, mannitol and lactose. The R factor of the coating powder material (Aerosil 200) was 25 and 30. The dissolution behavior of MC from liquisolid compacts was investigated in several buffered and biorelevant media with different pH values. The results showed that the drug release rates produced by liquisolid compacts prepared using Avicel with R factor 30 and 10% concentration of drug in glycerol formal were significantly higher and less affected by pH variation compared with marketed (Mosapride®) tablets. In conclusion, liquisolid compacts technique may be used as a tool to enhance solubility and dissolution and minimize the effects of pH variation on the dissolution rate of drugs with poor water solubility.f