Numerical Optimization of Prednisolone-Tacrolimus Loaded Ultraflexible Transethosomes for Transdermal Delivery Enhancement; Box-Behnken Design, Evaluation, Optimization, and Pharmacokinetic Study

• Published in: Gels Vol. 9; no. 5; p. 400
• Main Authors: Alfadhel, Munerah M, Zaki, Randa Mohammed, Aldosari, Basmah Nasser, Sayed, Ossama M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.05.2023; MDPI
• Subjects: Box–Behnken design; Corticosteroids; Design analysis; Design of experiments; Design optimization; Edema; Entrapment; Ethanol; Independent variables; Lipids; Nanoparticles; Physiological aspects; Prednisolone; Signal transduction; Steroids; Surfactants; Systems stability; Tacrolimus; transdermal delivery; Transdermal medication; transethosomes; Zeta potential; Japan; prednisolone; Box–Behnken design; transethosomes; transdermal delivery; tacrolimus
• ISSN: 2310-2861; 2310-2861
• DOI: 10.3390/gels9050400

The aim of the present study is to formulate highly permeable carriers (i.e., transethosomes) for enhancing the delivery of prednisolone combined with tacrolimus for both topical and systemic pathological conditions. A Box-Behnken experimental design was implemented in this research. Three independent variables: surfactant concentration (X1), ethanol concentration (X2), and tacrolimus concentration (X3) were adopted in the design while three responses: entrapment efficiency (Y1), vesicle size (Y2), and zeta potential (Y3) were investigated. By applying design analysis, one optimum formulation was chosen to be incorporated into topical gel formulation. The optimized transethosomal gel formula was characterized in terms of pH, drug content, and spreadability. The gel formula was challenged in terms of its anti-inflammatory effect and pharmacokinetics against oral prednisolone suspension and topical prednisolone-tacrolimus gel. The optimized transethosomal gel achieved the highest rate of rat hind paw edema reduction (98.34%) and highest pharmacokinetics parameters (Cmax 133.266 ± 6.469 µg/mL; AUC 538.922 ± 49.052 µg·h/mL), which indicated better performance of the formulated gel.