(M1230-07-43) Development and Evaluation of 2% (w/w) Apremilast Ointment for Psoriasis Management

Purpose: Psoriasis is a chronic autoimmune disorder in which the immune system mistakenly attacks healthy skin cells, leading to a rapid proliferation of skin cells that forms red, inflamed, and scaly patches. It affects over 8 million individuals in the United States and approximately 125 million people worldwide, representing about 2-3 % of the global population. The prevalence of psoriasis among African Americans is reported to be 1.5 %, compared to 3.6 percent in Caucasians. Apremilast is a selective phosphodiesterase 4 inhibitor used in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. It is currently available in tablet form; however, there are no commercially available topical formulations for the management of psoriasis. Apremilast has low solubility and poor skin permeability, which pose significant challenges for its dermal delivery. The objective of this study was to design and develop topical Apremilast formulation with a view to improving its permeation for management of Psoriasis.

Methods: In this study, a 2% (w/w) Apremilast ointment was developed using polyethylene glycol (PEG) as a base. PEG was selected as an ointment base considering the emollient and humectant properties, which can benefit psoriasis patients by moisturizing the skin. Procipient® DMSO, acting both as a solubilizer and permeation enhancer, was explored to improve the solubility and permeability of Apremilast through the skin. Given the tacky nature of PEG-based formulations, various excipients were tested to improve the sensory feel and patient compliance, aiming to develop a smooth, non-tacky, and stable ointment. The optimized formulation underwent various evaluation for parameters including assay, pH, viscosity, texture, and in-vitro release testing (IVRT). Additionally, stability studies were conducted in accordance with the ICH Q1A (R2) guidelines.

Results: The optimized 2% w/w Apremilast ointment demonstrated promising sensory and textural properties. The pH of the formulation was found to be 7.22, which is compatible with the skin’s natural pH, promoting skin health and reducing irritation. The viscosity of the formulation was found to be 496,000 cP with 49.6% torque, which is indicative of an adequately thick formulation suitable for topical application. Texture analysis revealed a hardness of 80.0 g, signifying that the formulation possessed an appropriate level of firmness for ease of application. The low cohesiveness value of 0.42 indicated that the ointment was non-sticky and relatively less cohesive, improving patient compliance. The springiness value of 9.9 mm indicated optimal elasticity, providing a smooth application without excessive residue. In-vitro release testing (IVRT), performed using a Franz diffusion cell, showed that 37.36 % ± 3.35 of Apremilast was released over 8 hours, demonstrating that the formulation allows for controlled drug release. Stability studies confirmed that the ointment maintained its stability under standard storage conditions.

Conclusion: The developed Apremilast ointment shows promising potential as a topical treatment for psoriasis, offering an alternative, patient-friendly route for drug delivery. The developed formulation addresses the solubility and permeability challenges associated Apremilast by providing a controlled release system with improved patient compliance due to its non-tacky, stable, and easily applicable nature.

References: 1. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis Prevalence in Adults in the United States. JAMA Dermatol. Published online June 30, 2021.
2. Sarango-Granda P, Silva-Abreu M, Calpena AC, Halbaut L, Fábrega MJ, Rodríguez-Lagunas MJ, Díaz-Garrido N, Badia J, Espinoza LC. Apremilast microemulsion as topical therapy for local inflammation: Design, characterization and efficacy evaluation. Pharmaceuticals. 2020 Dec 21;13(12):484.


Figure 1: Apremilast Ointment In Vitro Release as a Function of Time