Preparation and in vitro characterization of Valsartan solid dispersions using skimmed milk powder as carrier.

Solubility is an important physicochemical factor affecting absorption of drug and its therapeutic effectiveness. Consequences of poor aqueous solubility would lead to failure in formulation development. The poor solubility of drug substances in water and their low dissolution rate in aqueous G.I. T fluid often leads to insufficient bioavailability. In the present investigation, an attempt was made to improve the solubility and dissolution rate of a poorly soluble drug, Valsartan by solid dispersion method using skimmed milk powder as carrier. Four different formulations were prepared with varying drug: carrier ratios viz.1:1, 1:3, 1:5 and 1:9 and the corresponding physical mixtures were also prepared. The formulations were characterized for solubility parameters, drug release studies and drug-polymer interactions by using phase solubility studies, dissolution studies; XRD analysis, FTIR spectrum, TLC analysis and UV overlay spectra. All the formulations showed marked improvement in the solubility behavior and improved drug release. Formulation containing drug:polymer ratio of 1:9 showed the best release with a cumulative release of 81.60% as compared to 34.91 % for the pure drug. The interaction studies showed no interaction between the drug and the carrier. It was concluded that skimmed milk powder as a carrier can be very well utilized to improve the solubility of poorly soluble drugs. Key-words: Solid Dispersion, Skimmed milk powder, solubility, Valsartan, Dissolution INTRODUCTION The formulation of poorly soluble drugs for oral delivery now presents one of the major challenges to formulation scientists in the industry. Various formulation parameters that play a crucial role for successful formulation are aqueous solubility, stability at ambient temperature and humidity, photo stability, compatibility with solvents and excipients etc. Of these, solubility is the most important property for developing formulations. Compounds exhibiting dissolution rate limited bioavailability are considered class II according to BCS classification. As per recent report, 46% of the total NDAs filed between 1995 to 2002 were BCS class IV, while only 9% were BCS class I drugs, revealing that a majority of approved new drugs were water insoluble. There are drug candidates that have poor solubility in water but can be dissolved by suitable conventional formulation strategies which include, Co-solvents, Milling techniques, super critical processing, Solid dispersions including complexation, and precipitation techniques. Solid dispersion technique has often proved to be the most commonly used in improving dissolution and bioavailability of poorly soluble active pharmaceutical ingredients because it is simple, economic and advantageous. In solid dispersion technique, water soluble carriers are used to improve dissolution characteristics of poorly water soluble drugs. Valsartan is 3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5yl) Phenyl] methyl] amino]butanoic acid. It is white fine powder having poor aqueous solubility. The present study is an attempt to overcome the poor aqueous solubility of VALSARTAN by solid dispersion technique using skimmed milk powder (SMP) as carrier. MATERIALS & METHODS Valsartan was obtained as gift sample from Rubicon Reseacrh limited, Mumbai, Skimmed milk powder K.Venkates Kumar et al /Int.J. PharmTech Res.2009,1(3) 432 (SMP) was obtained from Himedia Laboratories, Mumbai. All other solvents and reagents used were of