Formulation and evaluation of self nano-emulsifying mouth dissolving film of azathioprine

Abstract

Self-nanoemulsifying mouth dissolving films (SNMDFs) integrate the benefits of self-nanoemulsifying drug delivery systems (SNEDDS) with fast-dissolving oral films, offering a potential solution to the instability of liquid SNEDDS. Azathioprine, a poorly water-soluble immunosuppressant, is used to prevent joint damage in autoimmune disorders. Development and evaluation of a solid SNMDF of azathioprine to enhance its stability, oral bioavailability, and patient compliance have been reported in this article. Liquid SNEDDS was converted into a solid SNMDF using Aerosil 200 and pullulan as solid carriers and film-forming polymers. A pseudo-ternary phase diagram was constructed using the water titration method. A 3² factorial design was used to optimize film formulation. The optimized SNMDF showed suitable mechanical and physicochemical properties: thickness (0.112 ± 0.061 mm), surface pH (6.2 ± 0.75), folding endurance (>200), and wetting time (~16 ± 3.16 sec). Upon reconstitution in water, a nanoemulsion formed with 208.6 nm particle size and 7.4 mV zeta potential. Drug release followed zero-order kinetics. Solid-state characterization indicated azathioprine reduced crystallinity and partial molecular dispersion of the drug within the polymer matrix. Azathioprine-loaded SNMDF presents a promising approach for improving stability, rapid onset, and oral bioavailability of poorly water-soluble drugs.