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.
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