You are hereFORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLETS FROM SOLID DISPERSIONS OF LOVASTATIN
FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLETS FROM SOLID DISPERSIONS OF LOVASTATIN
From the standard calibration curve of drug, it was concluded that drug obeys Beer-Lamberts law in concentration range of 0-50mcg/mL.
The dissolution data of plain drug in simulated gastric fluid showed that the release of the drug was less in both the medium and thus it was concluded that Lovastatin is poorly soluble drug and erratically absorbed throughout GI and also possess several dissolution related problem and that might be a reason for its poor bioavailability. Therefore, directly compressed tablet by using superdisintegrants and solid dispersion of drug were prepared by using different polymers. More stable polymers i.e. Crospovidone, Croscarmellose sodium and Sodium starch glycolate were used. The solid dispersions were prepared by solvent evaporation method as it is the easiest to perform and most preferred method.
The drug, solid dispersion and polymer were evaluated for the physical parameters. These physical parameters of solid dispersions and excipients concluded that these were considerably good to formulate the tablet using direct compression technique. The prepared tablets were characterized for physical parameters for each batch. Results reflected that all batches had desirable physical characteristics and had thickness, hardness, content uniformity, and friability values well within permissible range.
In vitro dissolution was carried out for each batch, and dissolution indicated release of Lovastatin which varied according to the quantity of matrix forming polymer. The tablets of batch K1-K6 were prepared using HPMC K100M with varying concentration. As the polymer used had higher the release was 72.22%, 74.97% and 56.21% in 12 hrs respectively. As the release was very less in stipulated time period the use of polymer was further discarded. However tablets of batch K5 sustained the release for 12 hours with cumulative drug release of about 99.08%. From dissolution data it was concluded that drug release rate decreased as the proportion of polymer increased than optimum.
Results of water uptake (swelling) and erosion study cleared that order of swelling observed in these polymers (HPMC) could indicate the rates at which the preparations were able to absorb water and swell. Maximum liquid uptake and swelling of polymer took place in the first 4-8 hours and then gradually decreased due to erosion. Exceptional to above observation batch K4-K6 showed linear increase in swelling as the concentration of the polymer is much greater to dominate the erosion phenomenon.
The observations of swelling and erosion studies of batch K1 to K6 clearly indicated the dual phenomenon i.e., of swelling and erosion, which could be observed visually. This might be due to the presence of poorly soluble Lovastatin with soluble HPMC, which results in the combination of polymer relaxation, which prevails in the first 4-8 hours and erosion, which dominates in the later stages (When erosion of the polymer becomes more intense). These findings were well supported by the Vlachos and co-workers.
The optimized batches of tablets were used for coating with hydroxylpropylmethyl cellulose phthalate of different concentrations of 5%, 8%, 10%. It was observed that tablets coated with HPMCP insoluble in gastric fluid and dissolve rapidly in the upper intestine. Among three batches, F3 (8% HPMCP) showed significant resistance to gastric release of drug and dissolves rapidly in upper intestine.
The optimized batch K5 and F3 were treated with different kinetic equations to interpret the order of release of Lovastatin and the coefficient of determination (r2) was determined. Results indicates that in the selected K5 formulation, the calculated regression coefficients for Zero order, First order, Hixson Crowell, Korsemeyer Pappas, Higuchi Plot models were 0.9860, 0.9868, 0.9589, 0.9269 and 0.9256 respectively. Therefore, the release seemed to fit in theKorsemeyer and Peppas diffusion model and the order in which the drug release was first - order kinetics. In this selected F3 formulation, the calculated regression coefficients for Zero order, First order, Hixson Crowell, Korsemeyer Pappas, Higuchi Plot models were 0.9559, 0.9876, 0.9642, 0.9298 and 0.9189 respectively. Therefore, the release seemed to fit in theKorsemeyer and Peppas diffusion model and the order in which the drug release was first - order kinetics.Further to characterize the release mechanism of Lovastatin from the tablets the dissolution data was subjected to Korsemeyer and Peppas diffusion model.
The values of n (diffusion exponent) were estimated by linear regression of log Mt / M∞ versus log (t). The value of n, for tablet batch K5 was found to be 1.1247 which depicts that the formulation exhibits a non-fickian release behavior, for tablet batch F3 was found to be 1.1605 which depicts that the formulation exhibits a non-fickian release behavior.
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