Formulation, Optimization, and Evaluation of a pH-Responsive In-situ gel of Tavaborole using Design of Experiments (DOE)

Onychomycosis, a chronic fungal infection of the nail, presents challenges in topical treatment due to the nail plate’s dense keratin structure and limited drug permeation. Tavaborole, a boron-containing antifungal agent, offers potent activity against dermatophytes but requires optimized formulations for effective transungual delivery. The present study aimed to formulate and optimize pH-responsive in-situ gels of Tavaborole using a Quality-by-Design (QbD) approach and Design of Experiments (DOE) methodology. Tavaborole was characterized as a clear, colorless liquid with no particulate matter, demonstrating purity and stability. Solubility studies revealed poor aqueous solubility but enhanced solubility in ethanol, methanol, and acetone, confirming its hydrophobic nature. UV-visible spectrophotometry at 272 nm provided a reliable method for quantitative analysis, with a linear calibration curve (R² ≈ 1.0). Various concentrations of Carbopol 934, HPMC K4M, and Triethanolamine were evaluated, significantly influencing viscosity (3426–4717 cps), gelation time (130–228 sec), pH (6.3–6.6), and drug release profiles. Formulations F12, F2, and F10 demonstrated the highest drug release (up to 92.51%) with suitable gelation and viscosity, ensuring effective and sustained topical delivery. FTIR analysis confirmed stable drug-excipient interactions, contributing to gel formation and controlled release behavior. Minimal bias percentages and predictive regression models validated the formulation process. Overall, the study establishes that the synergistic combination of Carbopol 934, HPMC K4M, and Triethanolamine enables the development of stable, patient-friendly, and efficient Tavaborole in-situ gels for onychomycosis treatment, with potential for improved therapeutic outcomes and patient compliance.