DEVELOPMENT OF NASAL DRUG DELIVERY SYSTEM OF ATORVASTATIN CALCIUM FOR ENHANCING BIOAVAILABILITY

Atorvastatin calcium is a synthetic lipid-lowering agent used in hyperlipidemia. An oral dose of Atorvastatin calcium ranges from 10mg to 80mg per day. Atorvastatin calcium belongs to BC’s class II drug having low solubility and high permeability. The absolute bioavailability of Atorvastatin calcium is approximately 12%, and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic availability attributed to presystemic clearance when given through oral route several approaches have been tried to improve the solubility of a drug by preparing oral formulation such as tablets, nanosuspension, nanoemulsions, and sustained release dosage forms, there was no article on nasal administration of Atorvastatin calcium. The objective of the present research study was to formulate and evaluate nasal solution containing Atorvastatin calcium 10 mg per 2 drops. As from saturation solubility studies of the drug in pure form, solid dispersions, and β-cyclodextrin inclusion complex of a drug, it was observed that the drug in a pure form showing greater solubility in propylene glycol. A nasal formulation containing Atorvastatin calcium in propylene glycol was prepared. To improve permeation, permeation enhancers such as SLS (1%), Tween 80 (1%), Chitosan (1% and 0.5%), EDTA (0.1%) were added. Formulations were evaluated for Appearance, color, clarity, PH, Drug content, Osmalarity, in-vitro, and ex-vivo permeation studies. Final optimized formulations showed good in-vitro and ex-vivo permeation and maintaining average flux value of 0.006mg/cm² for in-vitro and 0.017mg/cm² ex-vivo permeation. The best formulations were selected were selected for conducting further stability studies.