The effect of wetting agents on the dissolution of indomethacin solid dispersion systems

Abstract

Solid dispersion systems containing indomethacin and polyvinylpyrrolidone (PVP) 17 or 90 were prepared in drug: PVP ratios of 70 : 30, 80: 20 and 90 :10 by co-precipitation and spray drying. The polymorphic form of indomethacin in the systems was identified and physical mixtures containing the polymorphic form and the corresponding drug: PVP ratios were prepared for comparative purposes. Dissolution rates of indomethacin from the powdered systems were compared with that of the pure drug in water, in an aqueous polyethylene glycol (PEG) 300 solution and in 40 mM sodium cholate solution. Dissolution into PEG solution showed the drug dissolution rate from the systems depended upon the availability of drug to complex with PEG. In 40 mM sodium cholate solution, the dissolution rates of indomethacin from the systems were markedly enhanced due to favourable pH conditions, and were similar to one another, except for the indomethacin: PVP 17 co-precipitate which exhibited the fastest dissolution rate. The PVP 90 systems exhibited slightly slower dissolution rates in sodium cholate solution than the PVP 17 systems probably as a result of an increase in viscosity of the diffusion layer.