Atorvastatin calcium

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%.

The main objective of current research work was to develop a stable pharmaceutically equivalent combined dosage form of immediate release Atorvastatin calcium and extended release Metoprolol succinate formulation, which is comparable to that of innovator’s. Combination therapy affords the physician and the patient the opportunity to more effectively treat diseases that may stem from more than one cause. When used correctly and appropriately, combination therapy leads to better outcomes than mono therapy by treating more than one cause of the disease and/or by synergistically enhancing the action of one of the component drugs. The purpose of the study was to develop a capsule of Atorvastatin calcium (IR) and Metoprolol succinate (ER) having different release pattern, which is indicated for the management of hypertension. The study was planned in three stages. In the first stage three batches (A1, A2, and A3) of immediate release blend of Atorvastatin calcium was prepared using pre-gelatinized starch as super disintegrate. In the second stage, nine batches (M1-M9) of Metoprolol succinate sustained release pellets were prepared using various polymers and levels of coatings as rate retardants. Preformulation studies were performed after granulation. In the third stage capsules were evaluated for weight variation, drug content, and disintegration time and in vitro drug release using RP-HPLC. FTIR studies revealed no disturbances in the principle peaks of pure drugs and it confirms the integrity and compatibility of pure drugs with their excipients.