G. Gnanarajan*, Garima Thapliyal
Atorvastatin calcium (ATC) is the most effective and best tolerated agent for treating Coronary heart disease. ATC is unstable and at risk to heat, light, and moisture when packed in the form of tablets, powders, granules, or within capsules. In acidic environment it degrades into corresponding lactone. This instability of ATC leading to poor solubility is the main cause for low bioavailability of the drug after oral administration as the absolute bioavailability of ATC is only 14%. Therefore, aim of the research is to improve the oral bioavailability by formulating it into a fast dissolving sublingual film. Formulations were prepared composed of HPMC E15, HPMC K15M and Pectin as a film forming agent; Crospovidone, Sodium starch glycolate, and Croscarmellose sodium as a superdisintegrating agent; Polyethylene glycol as a plasticizer; citric acid as a saliva stimulating agent; mannitol as a sweetening agent; methanol and water as a solvent. Different film formulations of Atorvastatin calcium were prepared by using HPMC E15, HPMC K15M, Pectin, Crospovidone. Different formulations were prepared by varying concentration of (polymers and disintegrating agent) ratio by solvent casting method. The compatibility study of drug and excipients was performed by IR study and no interaction was found. The prepared films were clear, transparent and smooth surface. The percentage moisture uptake and percentage moisture loss were found to be high for the patches formulated with HPMC E15 and HPMC K15M when compared to the film formulated with pectin. Folding endurance of HPMC E15 and HPMC K15M containing films were found to be higher than the other films which might be due to the nature of the polymers. The formulations F1-F3 showed a better in vitro disintegration time (13-14 seconds), when compared to the other formulations. Optimized batch F1 containing containing hydroxy propyl methyl cellulose (500mg) and crospovidone(30mg) showed in vitro drug release (98.33%) within 6 minutes. The formulations F1 showed a better in- vitro permeation study profile (95.61 within 11minute), when compared to the other formulations. Keywords: Atorvastatin calcium, Coronary heart disease, bioavailability, fast dissolving sublingual film, film forming agent, in vitro dissolution study.