Optimization, evaluation and comparative IVPT study of micro and nano liposomal topical formulations of apremilast

Abstract

Atopic Dermatitis (AD) is an immune system-related, pruritic, chronically relapsing, skin inflammatory disease, which is more prevalent in children while it also affects adults. Apremilast (APT), available in market as a film-coated tablet for oral administration and is indicated for treatment of adult patients with active psoriatic arthritis. Apremilast is a BCS IV drug, has low permeability and solubility. Thus, prepared micro and nano-liposomes of apremilast for enhancement of permeability and compared with cetirizine and niacinamide using in-silico modeling approach. Liposomes were prepared by film hydration technique utilizing design experiment for optimization and evaluated their physicochemical properties such as particle size, PDI, entrapment efficiency, morphology by TEM, interaction study and in-vitro skin permeation test (IVPT) of both prototypes was performed using Franz Diffusion cell (cadaver skin). The prepared optimized liposome formulations showed particle size 2 ± 0.3 µm (microliposomes), 200 ± 31 nm (nanoliposomes), 0.18 ± 0.05 PDI and high entrapment efficiency (95.3 %). TEM image reveal that most of the particles were spherical and no tear was observed. Permeation test (IVPT) of both prototypes showed insignificant difference (p > 0.05) in the permeation of Apremilast delivered by micro-liposomes and nano-liposomes. The outcome of this study contradicted our hypothesis and the conclusion of many other published studies, which had demonstrated that delivery of drug molecules into skin depends on the particle size of liposome.