Toxicity Study of a Self-nanoemulsifying Drug Delivery System Containing N-methyl pyrrolidone.

Abstract

Recently within the lipid based formulation category, Self-nanoemulsifying drug delivery system (SNEDDS) has received considerable attention in the enhancement of bioavailability of poorly water-soluble drugs. Self-emulsifying formulation should have good solvent properties to allow appropriate solubility of the drug in the formulation. Drug incorporated in the formulation should also be readily dissolved as clear and monophasic liquid at ambient temperature when introduced to aqueous phase. N-methyl pyrrolidone (NMP) is one of the main pharmaceutical cosolvents and is a solubilizing excipient used in parenteral and oral medications. Marketed Leuprolide acetate (Sanofi-aventis, Quebec, Canada) is formulated as a solution composed of 55-66% NMP and 34-45% poly(DL-lactide-co-glycolide). Self-emulsifying oral formulation of fenofibrate containing NMP as solubilizer has been patented. Based on these reports we successfully developed SNEDDS formulation using NMP as cosolvent and found ~ 4 fold improvement in apparent permeability coefficient of model drug. To ensure the safety of the developed SNEDDS formulation, in the present study we further investigated its toxicity studies in mice and evaluated for various parameter. From the results it can be concluded that oral administration of SNEDDS formulation containing NMP did not exhibit significant toxicity in mice and further detail toxicity study is required so as to ensure the safety of this system in oral drug delivery.