Simvastatin

The aim of present work was to design and evaluate sustained release matrix tablets of antihyperlipidemic drug. In the present investigation, polymers used in different combinations such as Eudragit RL100 and HPMC E5 in the ratio of 1:1, 1:2, 1:3 and vice versa with PVP K25 using direct compression technique were prepared. The tablets were evaluated for physical parameters like thickness, hardness, friability, weight variation, and in vitro release studies. The FTIR study indicated that the drug is stable in formulation. The maximum drug release was found to be 94.41% over a period for 12 hours for F4 batch, thus concluded that as the concentration of Eudragit RL100 is increased the drug release decreased. The drug release mechanism followed non-fickian transport from both polymer matrices. All the formulations were stored at 250C/60% RH and 450C/75% RH for 3 months. It showed that all the formulations were physically and chemically stable.

The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years.  The objective of this present investigation was to develop extended release (ER) trilayer matrix tablets containing simvastatin solid dispersion prepared by direct compression and consisted of middle active layer with different grades of hydroxypropylmethylcellulose (HPMC), guar gum, ethyl cellulose. Upper and lower layers are prepared with Carnauba wax, guar gum and carbopol 934P. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF14) was described by the Zero-order and Higuchi model. In-vivo bioavailability studies were carried out with the optimized formulation (HF14) and reference standard.  A fair correlation between the dissolution profile and bioavailability for the optimized formulation was observed. The results indicate that the approach used could lead to a successful development of a trilayer extended release formulation up to 24h. These results also demonstrated that the Simvastatin solid dispersion incorporated trilayer tablets shown more bioavailability because of its conversion from crystalline to amorphous form.

The aim of the present study is to enhance solubility of simvastatin by solid dispersion technique. Solid dispersions were prepared by fusion method by using various polymers. Formulation is optimized on the basis of acceptable solid dispersion properties and in-vitro release. In order to obtained best optimized product, 5 different formulations were developed. Different polymers like PEG 6000, HPMC 6000,HPC 1000 were taken as variables. Angle of repose, carr’s index, particle size, drug content and dissolution study were studied as response variables. The different physical properties showed best comparable results with drug. But higher percentage of drug release was observed when the formulation contained PEG6000 in 1:1.5 ratio (f5) compared to other formulations. Form this study it concluded that formulation (f5) which contained PEG (1:1.5) as polymer showed best dissolution profile compared to the drug. The formulation contained PEG 6000 was selected as optimized product.

A new, simple, accurate, precise and reproducible RP-HPLC method for the simultaneous estimation of Sitagliptin Phosphate Monohydrate and Simvastatin has been developed and validated. Chromatographic separation was achieved using Neosphere C-18 column (4.6 mm 250mm,5mm) in gradient mode with a mobile phase consisting a mixture of acetonitrile:methanol:0.1% orthophosphoric acid in water (70:15:15v/v) at a flow rate of 1ml/min. The eluents were detected at 254 nm using UV detector. The retention time of Sitagliptin Phosphate Monohydrate and Simvastatin were found to be 2.09min and 7.79min respectively. The method was linear over the concentration range of 25-150μg/mL for Sitagliptin Phosphate Monohydrate and 10-60μg/mL for Simvastatin. The % recoveries for Sitagliptin Phosphate Monohydrate and Simvastatin were found to be 98.98-101.06% and 99.89-102.43% respectively. The developed method was validated for parameters like system suitability, specificity, linearity, accuracy, precision, ruggedness and robustness as per International Conference on Harmonization guidelines and the results were found to be within the limits. This validated method can be used for the routine quality control analysis of Sitagliptin Phosphate Monohydrate and Simvastatin in combined dosage form.

A new, simple, specific, sensitive, rapid, accurate and precise RP-HPLC method was developed for the estimation of Simvastatin in bulk and pharmaceutical formulations. Simvastatin was chromatographed on a hypersil C18 column (250x4.6mm I.D., particle size 5 μm) in a mobile phase consisting of sodium dihydrogen phosphate and Acetonitrile in the ratio 40:60 v/v. The mobile phase was pumped at a flow rate of 1.0 ml/min with detection at 239 nm. The detector response was linear in the concentration of 10-200 μg/ml. The intra and inter day variation was found to be less than 2%. The mean recovery of the drug from the solution was 99.39%. The proposed method is simple, fast, accurate, precise and reproducible hence, it can be applied for routine quality control analysis of Simvastatin in bulk and pharmaceutical formulations.