PHYSICOCHEMICAL ASPECTS OF DRUG RELEASE .11. TABLETING PROPERTIES OF SOLID DISPERSIONS, USING XYLITOL AS CARRIER MATERIAL

A set of tests, including characterization of carrier fragmentation tendency, radial and axial tablet tensile strength, friability, disintegration time and dissolution rate, is presented for the evaluation of the suitability of substances to be used as carriers in solid dispersions prepared by the melting method. The carrier used as a model substance was the sugar alcohol xylitol. Solid dispersions of the sparingly soluble drug griseofulvin were prepared at three concentrations (2, 10 and 20% w/w) by the melting method. Tablets were made of pure untreated xylitol, of fused/recrystallized xylitol and of solid dispersions with external lubrication or with lubricant included in the composition. In some of the compositions the binding/disintegrating agents Avicel and Ac-Di-Sol were included. It was observed that xylitol fragments extensively. The tableting properties were somewhat improved if xylitol was fused/recrystallized. The incorporation of griseofulvin increased the tablet tensile strength. This indicates that conclusions regarding tableting properties cannot be made directly from studies of an untreated carrier. Thus, the set of tests can be a valuable tool in tablet formulation. The fastest drug dissolution was obtained with solid dispersions of the lowest concentration of drug in both particulate and tablet form. An increase in drug content and compression pressure and a decrease in rotational paddle speed decrease the dissolution rate. Internal lubrication with the admixing of 0.5% magnesium stearate prior to tablet compression had a limited retarding effect on the dissolution rate.