Central composite design (CCD) based formulation, optimization, in-vitro and ex-vivo characterization of 5-fluorouracil-loaded emulgel for enhanced dermal penetration and psoriasis management.

Abstract

ObjectivePsoriasis is a condition that mostly responds to topical remedies. 5-FU is promising since it is anti-proliferative but has poor permeability. The study aimed to fabricate a novel 5-FU emulgel in order to accomplish enhanced therapy of psoriasis. Methods: A Central Composite Design (CCD) was employed to optimize the emulgel's key characteristics, including viscosity, spreadability, drug content, and in-vitro release profile. This statistical approach utilized a five-level, two-factor model to construct linear and quadratic relationships between the formulation variables and the desired responses. Design-Expert software (Version 13) facilitated this process, requiring thirteen experimental runs (FU1-FU13) to achieve optimal formulation parameters. The emulgel consisted of an oil phase (oleic acid, Span 80, and Transcutol P) and an aqueous phase (5-FU and Tween 80). High shear homogenization was utilized for emulsification. The emulsion and gel were combined in a 1:1 ratio to form the emulgel. Finally, the optimized emulgel (FU13) underwent assessments for drug-excipient compatibility, ex-vivo drug permeability through the skin barrier, and long-term stability. Results: The results of optimized formulation FU13 showed viscosity of 5166 ± 9.01 Pa.s, spreadability of 27.56 ± 2.69 g.cm/s, extrudability of 28.49 ± 2.25 g/cm, drug content of 87.9 ± 3.16%, in-vitro drug release of 96.4 ± 1.25 up to 360 mins and ex-vivo cumulative permeability of 1056.97 ± 10.33 µg/cm². FU13 showed no significant chemical interactions and was stable throughout stability period. Conclusion: It is within this context that the present study appears to possess significant potential for topical treatment of psoriasis, as it provides higher therapeutic gain over current treatment modalities with fewer undesired effects.