In vitro and preclinical assessment of factorial design based nanoethosomal transdermal film formulation of mefenamic acid to overcome barriers to its use in relieving pain and inflammation

Abstract

Mefenamic acid (MA) is a non-steroidal anti-inflammatory drug with analgesic activity. Marketed MA tablets or capsules often result in gastrointestinal disorders, such as upset and bleeding. MA also has poor solubility and short half-life (2 h), which requires frequent dosing, leading to higher incidence of side effects. The objective was to develop a statistically optimized nanoethosome (NE) formulation of MA loaded into transdermal films, as an alternative to oral delivery, to offer an extended release behavior. Box-Behnken design was used to analyze the effect of phospholipid concentration, ethanol concentration, and ultrasonication time. On three variables, particle size, entrapment efficiency, and steady state flux. Optimized MA-loaded nanoethosome formulation was prepared using a thin layer evaporation technique. Further, the nanoethosomal-loaded transdermal film was evaluated for in-vitro release, ex-vivo permeation, and in-vivo pharmacokinetics studies. The optimized formula indicated particle size of 97 nm with 80% of entrapment efficiency. Enhanced skin permeation of MA was more than 3.4 folds higher for nanoethosomes loaded films in comparison to pure drug transdermal films The estimated steady state flux was 2 and 15 mcg/cm2 min. The bioavailability studies indicated that mean AUC0-48 increased by 4-folds after transdermal delivery of optimized nanoethosomal film with no side effects.