Fabrication and characterisation of nabumetone transferosomal gel for effective topical delivery

Abstract

Nabumetone is a lipophilic drug with a log P value of 3.2 and belongs to BCS class II due to its poor water solubility. When administered orally, it undergoes extensive first-pass metabolism, shows low bioavailability, and has unfavourable side effects that cause discomfort. Topical route has gain importance by delivering therapeutic agents via this route due to its safety and convenience of drug administration and as of there are no any gel formulations available for it. The present investigation aimed to prepare, optimise, and characterise Nabumetone-loaded transferosomes (Nb-TF) using 32 factorial designs. Transferosomes were prepared by the thin-film hydration method. The optimised formulation was incorporated into gel form (Nb-TG) and evaluated for its mechanical characteristics, in-vitro release, ex-vivo permeation, skin irritancy test, anti-inflammatory activity, and stability studies. The Nb-TF 5 transferosomal formulation was optimised based on vesicle size and entrapment efficiency and incorporated into the gel base. Both normal (Nb-gel) and transferosome-loaded (Nb-TG) gel pH was within the range of topical skin pH. The viscosities of Nb-gel and Nb-TG were 1262 ± 54 cP and 1327 ± 12 cP, respectively. The drug content of both gels was found to be 96.31 ± 1.16 and 97.18 ± 0.94, respectively. Nb-TG showed higher diffusion and drug permeation than Nb-gel. The skin irritancy test indicates that there was no sign of any edema or erythema observed. Nb-TG showed a curative and preventive anti-inflammatory effect. Gels were found stable at both refrigerator and room temperature. Nb-TFs were proven to be potential carriers for transdermal controlled delivery of Nabumetone as it has deep penetration in the dermis layer which directly goes into the systemic circulation, enhances the bioavailability and reduced toxicities.