Formulation and performance evaluation of betahistine dihydrochloride microspheres as sustained release systems.

UNLABELLED Betahistine dihydrochloride is a histamine-like drug widely used in relieving the symptoms associated with Ménière's syndrome. Pharmacokinetic studies of betahistine have demonstrated that it has a short plasma half-life of 3-4 hours. In such cases frequent administration of the drug is required in order to keep plasma concentration within the therapeutic range. However, this may lead to noncompliance and aggravate patients' comfort. An advanced approach for achieving sustained release of drugs is their incorporation in microparticulate carriers. AIM To design a sustained release microsphere formulation of betahistine providing reduced dose frequency and lower risk of side effects occurrence. MATERIALS AND METHODS Betahistine-loaded chitosan microspheres were obtained via W/O emulsion solvent evaporation technique and were characterized for particle size, drug loading and entrapment efficiency. Drug release into phosphate buffer saline pH 7.4 was performed and dissolution profiles of the formulations were obtained. To study the mechanism of drug release from the microspheres the dissolution data was fitted to various mathematic models. RESULTS Betahistine-loaded microspheres were produced with a high drug loading and entrapment efficiency. The microcarriers were spherical in shape with mean particle size of 3.82 μm to 7.69 μm. Betahistine release studies from the microspheres showed similar and slightly increasing dissolution profiles. The drug release proceeded in a controlled manner following Fickian diffusion. CONCLUSION The obtained results suggest that betahistine-loaded chitosan microspheres prepared by solvent evaporation method are capable of sustained release of drugs and therefore can be used as drug delivery systems in the treatment of Ménière's syndrome.