TRANSDERMAL DELIVERY OF AZATHIOPRINE BY SOLID LIPID NANOPARTICLES: IN-VITRO AND EX-VIVO STUDIES

The aim of the present study was to prepare solid lipid nanoparticles (SLNs) of azathioprine to increase its permeability and to develop azathioprine loaded solid lipid nanoparticles (AZA SLNs) based transdermal film for topical administration with the aim of reducing systemic and gastro-intestinal side effects of the drug and achieve passive targeting of drug to the joint due to enhanced permeability and retention (EPR) effect. Azathioprine SLNs were prepared by hot homogenization technique and optimized by 3² factorial design to evaluate the impact of the formulation variables on the dependent variables. Optimized formulation was evaluated for various in-vitro attributes and then incorporated into a transdermal film by a solvent casting method, which was evaluated for various technological properties and ex-vivo permeability study. Size of the optimized SLNs was found to be 113.3 ± 5.09 nm with 0.308 ± 0.008, polydispersity index (PDI) and encapsulation efficiency of 80.28 ± 1.29%. The in-vitro release studies of optimized formulation showed sustained release up to 24 h possessing biphasic pattern with a burst release during the first 8 h. Film loaded with AZA SLNs showed cumulative percent release (% CPR) of 78.97 ± 1.242% at the end of 24 h for formulation FT₄ consisting propylene glycol and DMSO as a permeation enhancer. Drug-excipient compatibility studies revealed no drug-excipient incompatibility. Thus it can be concluded that transdermal film loaded with AZA SLNs represents a promising drug delivery system for the treatment of rheumatoid arthritis.