Solubility and dissolution enhancement of poorly aqueous soluble drug atorvastatin calcium using modified gum karaya as carrier: In vitro-In vivo evaluation
Keywords:
Solid dispersion, solubility, dissolution, atorvastatin calcium, gum karaya, modified gum karaya, kneading, co-grinding, solvent evaporation, amorphous, crystallineAbstract
Solid dispersion is a unique and promising approach for improving the oral absorption and oral bioavailability of BCS class II drugs. Modified gum karaya a recently developed excipient was evaluated as a carrier for solubility and dissolution enhancement of poorly water soluble drug atorvastatin calcium. Physical mixtures along with solid dispersions of drug and polymer was prepared using three methods kneading, solvent evaporation and solvent wetting method in 5 different ratios (1:1,1:3,1:5,1:7,1:9). Among the three methods used atorvastatin calcium solid dispersions prepared by kneading method in 1:3 ratio showed most promising results in terms of percent yield, percent drug content, solubility of solid dispersions in phosphate buffer pH 6.8, XRD, DSC, SEM and In vitro release studies. These solid dispersions were selected to prepare tablets using Ac-di-sol as superdisintegrant (T1, T2, T3, T4 and T5). Tablets were characterized for hardness, friability, disintegration time, percent drug content, drug release studies and stability studies. Tablets T5 showed highest dissolution rate and best dissolution efficiency at (DE30) and (DE120) minutes. Release data of T5 tablet was subjected to various release kinetics models to know the type and order of drug release. Order was found to be Korsemeyer–Peppas>Hixson– Crowell cube root law >zero-order >first-order >Higuchi. The similarity factor was calculated for comparison of the dissolution profile before and after stability studies. The f2 value was found to be more than 50 (~ 90.9) thereby indicating a close similarity between both the dissolution profiles. In vivo studies was conducted on healthy albino rats and formulation given by oral route showed that at the end of 14 days solid dispersion 1:3 performed better than pure atorvastatin calcium in reducing total cholesterol and TG level and increasing HDL- cholesterol levels.
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