Formulation and ex vivo permeation evaluation of ketotifen-loaded microemulgels for topical delivery

Developing patient-friendly and non-invasive topical drug delivery systems is essential for improving therapeutic efficacy and patient compliance. In this study, ketotifen (KTF)-loaded microemulgels (μEGs) were formulated using biocompatible ingredients for enhanced topical delivery. Microemulsion (μE) systems composed of castor oil, Emulan EL, isopropanol, and water with varying surfactant/co-surfactant ratios (S mix ) were developed to systematically investigate the influence of formulation composition on microstructural characteristics and topical drug delivery performance and subsequently gelatinized using PEG-6000 and Poloxamer 407 to achieve controlled skin permeation. Pseudoternary phase diagram analysis identified optimized formulations containing ∼11% castor oil, ∼14% water, and ∼75% S mix , capable of incorporating ∼2.5 wt% KTF. Conductivity and viscosity analyses confirmed phase transitions from water-in-oil (w/o) to oil-in-water (o/w) systems through a bicontinuous phase. Transmission electron microscopy and dynamic light scattering revealed monodisperse nano-sized droplets with sizes ranging from ∼49–95 nm for μEs and ∼61–120 nm for KTF-loaded μEGs. Ex vivo permeation studies using rabbit skin in a Franz diffusion cell at pH 7.4 demonstrated enhanced permeation, with μEGs achieving >90% drug release after 12 h. The improved performance was attributed to their nanoscale droplet size and higher viscosity, and the combined physicochemical and permeation analyses established a clear relationship between formulation composition, microstructural evolution, and topical permeation behavior. These findings provide mechanistic insight for the rational optimization of μE-based topical drug delivery systems.