Formulation Development and Evaluation of Proniosomal Gel containing Crisaborole

Introduction: Atopic dermatitis is a prevalent chronic inflammatory skin disorder, characterized by pruritus and the formation of eczematous lesions, significantly impairing the quality of life. Crisaborole, a non-steroidal phosphodiesterase-4 inhibitor, has shown promise in the treatment of Atopic Dermatitis due to its anti-inflammatory properties. However, the development of an efficient topical delivery system for Crisaborole remains a challenge, necessitating innovative approaches to enhance its skin permeability and therapeutic efficacy. Objective: This study aimed to develop and optimize a proniosomal gel formulation of Crisaborole, utilizing the coacervation phase separation technique in conjunction with a 32 full factorial design, to achieve enhanced drug encapsulation and sustained release for effective management of Atopic Dermatitis. Methodology: Proniosomes, as colloidal carriers, consist of non-ionic surfactants, soya lecithin, and cholesterol, which upon hydration, self-assemble into niosomes. These systems are known for their ability to enhance drug stability, bioavailability, and permeation. The coacervation phase separation method was employed to encapsulate Crisaborole within proniosomal vesicles, aiming to improve its topical delivery. The 32 full factorial design was utilized to systematically assess the effects of two independent variables on-ionic surfactant (X1) and cholesterol (X2) on critical parameters, including vesicle size and entrapment efficiency. Results: Optimized formulations were identified based on factorial analysis, with the most promising batch exhibiting a vesicle size of 175 nm and an entrapment efficiency of 87.57±0.020%. The proniosomal gel formulation was comprehensively characterized for parameters such as vesicle size, morphology, viscosity, spreadability, extrudability, drug release, and stability. In vitro release studies indicated a sustained release profile, suggesting prolonged topical efficacy. Conclusion: The optimized Crisaborole proniosomal gel demonstrated favourable physicochemical properties, including small vesicle size and high entrapment efficiency, making it a suitable candidate for the topical treatment of Atopic Dermatitis. The sustained drug release from the proniosomal system indicates its potential to enhance therapeutic outcomes through prolonged skin residence time and improved drug penetration.