Content area
Full Text
In the present investigation, mixed-solvency approach was applied for the enhancement of aqueous solubility of a hydrophobic drug by making blends of selected water-soluble substances from among the hydrotropes (urea, sodiumbenzoate, sodium citrate, nicotinamide); and cosolvents (propylene glycol, glycerine, PEG-200, PEG-300, PEG-400, PEG-600) precluding use of organic solvents and attempt was made to developed new oral solution (syrup) formulation. Analgesic, anti-inflammatory and ulcerogenic effect of newly developed oral solution (syrup) formulation (IOS4) of indomethacin using mixed solvency concept were evaluated in laboratory animals. Prepared formulation contains 40% mixed solvents as vehicle (% combination of UR, SC, PEGTH, PEGFH, PEGSH, GLY and PG) for drug. Acetic acid induced writhings and carrageenan induced paw edema methods were used to screened analgesic and anti-inflammatory activity of pure drug and formulation. Developed formulation IOS4 exhibited significant (P<0.0001) analgesic and anti-inflammatory effect as observed in paw edema model. The severity of gastric lesion of standard pure drug and formulation were also insignificant (P< 0.05).
INTRODUCTION
The formulation of solutions presents many technical problems to the industrial pharmacist (Savjani et al. 2012). It has been estimated that roughly 40% of all investigational compounds fail development because of poor bioavailability that is often associated with aqueous insolubility (Prentis et al. 1988). Different techniques are available for solubilization of the poorly water soluble drugs. Hydrophobic drugs completely absorb only when they show fair solubility in gastric medium after oral administration. Drug solubility in an aqueous medium and drug permeability through lipophillic membranes are the essential factor which governs drug's bioavailability (Chaudhary 2012). A large number of organic solvents like ethanol, methanol, ethylacetate, dimethyl sulfoxide, toluene, chloroform, dimethylformamide, acetonitrile, carbon tetrachloride, acetone, hexane etc. have been employed for solubilization of poorly water-soluble drugs. Drawbacks of organic solvents include higher cost, toxicity and pollution. Organic solvents have innumerous adverse effects caused by single exposure like nausea, eye irritation and long term exposure causes serious effects such as neurological disorders, chronic renal failure, liver damage, necrosis, mutagenesis disorder. They should be replaced by other eco-friendly alternative sources. The present investigation is an attempt to show that mixed solvent system can be wisely used to act as solvent precluding the use of organic solvents. Maheshwari et al. have demonstrated the synergistic solubilizing capability due to mixed...