Atorvastatin Calcium Solid Dispersion in Floating Tablets for Hypolipedmic Effect.

The aim of this study was increasing the bioavailability of poorly water soluble, atorvastatin calcium (ATC) via preparation of solid dispersion then incorporating it in floating tablets for oral use. Physical mixtures of ATC were prepared by mixing the appropriate amounts of ATC and carriers (PVP k-2000, PEG 6000 and skimmed milk) in geometric proportions using a mortar and pestle, until a homogeneous mixture was obtained. Solid dispersions of ATC with all carriers   were prepared at ratios of (1:1, 1:3, 1:5, 1:7 and 1:9 drug to carrier ratio w/w) by three methods, kneading method, solvent evaporation and melting method. Evaluation of solid dispersion was done by studying the phase solubility, in-vitro dissolution, FTIR spectroscopy, DSC and X-ray powder diffractometry. The selected solid dispersion formulation was incorporated in floating tablets which were prepared by melting granulation method. Evaluation of floating tablets was done by determination of tablet thickness, diameter, weight uniformity, content uniformity, hardness, friability, in-vitro dissolution, in-vitro buoyancy in addition to bioavailability studies. PEG 6000, PVP k-2000 and skimmed milk increased the solubility of ATC by 180, 290 and 1200 folds, respectively. Solid dispersion prepared using PEG 6000 (S2, 1:3 drug: polymer ratio) gave the highest % drug released than PVP k-2000 and skimmed milk. Floating tablet formulation (T1) showed the best drug dissolution rate which is 102.18% after 24 h. Bioavailability results showed that floating tablets containing ATC solid dispersion is effectively used for treatment of hyperlipedmia. Floating tablets contained PEG 6000 solid dispersion reduced the % of TC, TGS and LDL by 58.46, 32.00 and 91.21 %, respectively while the percent of HDL was raised by 11.11%.