Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the transdermal delivery of OXC from microemulsions using different penetration enhancers. Transcutol^® P (TRC), oleic acid (OA), cineole (cin), Labrasol (LS), Tween 80 (T80) and N-Methyl-Pyrrolidone (NMP) were used as penetration enhancers as well as microemulsion components. Simple formulations of OXC in propylene glycol (PG) incorporating various penetration enhancers and combination of penetration enhancers were also evaluated for transdermal delivery. Drug delivery and penetration enhancement were studied using human cadaver skin on Franz diffusion cells. The results showed that all penetration enhancers improved the rate of permeation of OXC compared to the control. The flux of drug delivery from the various formulations was found to be, in decreasing order, cin > OA + TRC > NMP > TRC > OA. Overall, microemulsions prepared using cineole, Tween 80 and Transcutol^® P (TRC) were shown to be provide the best penetration enhancement for OXC.

The fungal disease of the nail, onychomycosis, which is also the most prevalent nail disturbance, demands effective topical treatment options considering the possible adverse effects of systemic antifungal therapy. The current work is focused on development of an adhesive and resistant, drug-delivering and permeation-enhancing polymeric film containing econazole nitrate (ECN) for topical antifungal treatment. The development of the lacquer formulation was guided by the Quality by Design approach to achieve the critical quality attributes needed to obtain the product of desired quality. Eudragit RSPO at 10% w/w was found to be the ideal adhesive polymer for the application and an optimal permeation-enhancing lacquer formulation was achieved by the optimization of other formulation excipients, such as plasticizer and the solvent system. Additionally, novel experimental enhancements introduced to the research included refined D₅₀ drying time and drying rate tests for lacquer characterization as well as a multi-mechanism permeation-enhancing pre-treatment. Moreover, a practical implication was provided by a handwashing simulation designed to test the performance of the lacquer during actual use. In vitro drug release testing and ex vivo nail permeation testing demonstrated that the optimized nail lacquer performed better than control lacquer lacking the permeation enhancer by achieving a faster and sustained delivery of ECN. It can be concluded that this is a promising drug delivery system for topical antifungal treatment of onychomycotic nails, and the novel characterization techniques may be adapted for similar formulations in the future.

Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, possesses diverse therapeutic properties for skin conditions. However, formulating TQ presents challenges due to its hydrophobic nature and chemical instability, which hinder its skin penetration. Transethosomes, as a formulation, offer an environment conducive to enhancing TQ’s solubility, stability, and skin permeation. To optimize TQ transethosomal formulations, we introduced a combination of ionic and nonionic surfactants, namely Tween 20 and sodium lauryl sulfate (SLS) or sodium lauroyl glutamate (SLG). Surfactants play a crucial role in stabilizing the formulation, reducing aggregation, improving biocompatibility, and minimizing potential toxicity. We fine-tuned the formulation composition and gained insights into its interfacial behavior using the Langmuir monolayer technique. This method elucidated the interfacial properties and behavior of phospholipids in ethosome and transethosome formulations. Our findings suggest that monolayer studies can serve as the initial step in selecting surfactants for nanocarrier formulations based on their interfacial dilational rheology studies. It was found that the addition of surfactant to the formulation increased the elasticity considering the capability of transethosomes to significantly decrease their radius when permeating the skin barrier. The results of the dilational rheology experiments were most relevant to drug permeation through the skin for the largest amplitude of deformation. The combination of Tween 20 and SLS efficiently modified the rheological behavior of lipids, increasing their elasticity. This conclusion was supported by in vitro studies, where formulation F2 composed of Tween 20 and SLS demonstrated the highest permeation after 24 h (300.23 µg/cm²). Furthermore, the F2 formulation showed the highest encapsulation efficiency (EE) of 94%, surpassing those of the control and ethosomal formulations. Additionally, this transethosomal formulation exhibited antimicrobial activity against S. aureus, with a zone of inhibition of 26.4 ± 0.3 mm. Importantly, we assessed the cytotoxicity of both ethosomes and transethosomes at concentrations ranging from 3.5 µM to 50 µM on HaCaT cell lines and found no cytotoxic effects compared to TQ hydroethanolic solution. These results suggest the potential safety and efficacy of TQ transethosomal formulations.

Background/Objectives: Adapalene is a synthetic retinoid used as a treatment for acne vulgaris. In this study, we attempted to evaluate the dermal pharmacokinetics of adapalene utilizing experimental and in silico tools. Methods: We utilized three over the counter (OTC) adapalene gels to evaluate local dermal pharmacokinetics. A data-driven, robust, mechanistic dermal physiologically based pharmacokinetic (PBPK) model was developed by integrating the physicochemical properties of adapalene, the formulation attributes of the gels, and the biophysical aspects of dermal absorption. The dermal PBPK model was validated against experimental data using in vitro release studies and in vitro permeation studies with human cadaver skin. A clinical study was performed to evaluate the effects of adapalene from the three gel formulations. The impact of adapalene delivery from three gels on the stratum corneum (SC) thickness, pilosebaceous unit area, keratinocyte number, and epidermal thickness was captured using a non-invasive technique, line-field confocal optical coherence tomography (LC–OCT). These responses were evaluated using an Emax model. Results: The dermal PBPK model has successfully predicted adapalene penetration profiles across different gel formulations. The model accuracy, in predicting drug release and permeation characteristics, was confirmed using the experimental data. Clinical evaluation revealed formulation-dependent differences in adapalene’s effects on measured skin parameters, with distinct pharmacodynamic profiles observed for each gel formulation. Conclusions: The overall study gave us a detailed insight into potential effects of formulation on the dermal pharmacokinetics and pharmacodynamics of adapalene using three marketed gels.

The bioactive compound, thymoquinone (TQ), found in Nigella sativa seeds is known for its various therapeutic properties. Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, is known for its various therapeutic properties. However, TQ as a compound is challenging for a pharmaceutical formulator due to its hydrophobic nature and chemical instability, limiting its skin penetration. Transethosomes, as a formulation, provide an environment that enhances the solubility of TQ, stability, as well as skin permeation. To optimize TQ transethosomal formulations, we introduced a combination of surfactants namely nonionic Tween 20 and ionic sodium lauryl sulfate (SLS) or sodium lauroyl glutamate (SLG). These surfactants stabilize the formulation, reduce aggregation, and improve biocompatibility, as well as minimizing potential toxicity. Using the Langmuir monolayer technique, we fine-tuned the formulation composition and gained insights into its interfacial behavior. We conducted skin penetration studies using Rhodamine B as a model lipophilic compound to understand the skin penetration mechanisms. Our findings revealed that the transethosomes formulation, a combination of ionic and nonionic surfactants in the F2 formulation, resulted in the smallest particle sizes (115.4 nm) and demonstrated the highest skin permeation after 24 hours (267.13 μg/cm²), surpassing the control and ethosomal formulations. Additionally, this transethosomal formulation exhibited antimicrobial activity against S. aureus, with a zone of inhibition of 26.4 ± 0.3 mm. Importantly, we assessed the cytotoxicity of both ethosomes and transethosomes at concentrations ranging from 3.5 μM to 50 μM on HaCaT cell lines and found no cytotoxic effects in comparison to TQ solution controls. These results suggest the potential safety and efficacy of these TQ formulations and their further development in skin delivery.

Transdermal drug delivery offers several advantages over conventional routes. However, its use is limited by the low permeability of the stratum corneum. This limitation is especially significant in the case of hydrophilic drugs such as caffeine. This study explored microemulsion systems to enhance the transdermal delivery of caffeine (CF) using chemical penetration enhancers as cosurfactants. Kolliphor^® PS80 (PS80), Kolliphor^® RH40 (RH40), Kolliphor^® PS20 (PS20), and Kollicream^® OD (OD) were evaluated as cosurfactants for the first time in microemulsion formulations consisting of water, oil, and a fixed surfactant-to-cosurfactant ratio of 4:1 (w/w), with 14% of each cosurfactant incorporated. CF skin permeation from microemulsions was assessed via in vitro permeation studies using Franz diffusion cells and human cadaver skin. The results showed that OD-based microemulsions achieved approximately 3-fold higher CF skin permeation compared with the control formulation and 1.4–1.6-fold higher permeation compared with formulations containing PS80, RH40, and PS20. Furthermore, CF solubility in the four cosurfactants followed the order: PS20 > RH40 > PS80 > OD. These findings indicate that PS20 provides the highest solubility for CF among the tested cosurfactants. The results also included visual evaluations. No significant changes in appearance or physical properties were observed during the 10-month study. All samples remained clear and stable throughout the testing period. This study uniquely highlights the critical role of cosurfactant selection in optimizing microemulsion-based transdermal delivery systems. This work addresses a previously unexplored aspect, namely, the effect of cosurfactants with different physicochemical properties on the skin permeation of caffeine. The findings provide valuable insight into developing more effective transdermal and topical drug delivery systems.