Microemulsified Gel Formulations for Topical Delivery of Clotrimazole: Structural and In Vitro Evaluation

Abstract

Microemulsified gels (μEGs) with fascinating functions have become indispensable as topical drug delivery systems due to their structural flexibility, high stability, and facile manufacturing process. Topical administration is an attractive alternative to traditional methods because of advantages such as noninvasive administration, bypassing first-pass metabolism, and improving patient compliance. In this article, we report on the new formulations of microemulsion-based gels suitable for topical pharmaceutical applications using biocompatible and ecological ingredients. For this, two biocompatible μE formulations comprising clove oil/Brij-35/water/ethanol (formulation A) and clove oil/Brij-35/water/1-propanol (formulation B) were developed to encapsulate and improve the load of an antimycotic drug, Clotrimazole (CTZ), and further gelatinized to control the release of CTZ through skin barriers. By delimiting the pseudo-ternary phase diagram, optimum μE formulations with clove oil (∼15%) and Brij-35 (∼30%) were developed, keeping constant surfactant/co-surfactant ratio (1:1), to upheld 2.0 wt % CTZ. The as-developed formulations were further converted into smart gels by adding 2.0 wt % carboxymethyl cellulose (CMC) as a cross-linker to adhere to the controlled release of CTZ through complex skin barriers. Electron micrographs show a fine, monodispersed collection of CTZ-μE nanodroplets (∼60 nm), which did not coalesce even after gelation, forming spherical CTZ-μEG (∼90 nm). However, the maturity of CTZ nanodroplets observed by dynamic light scattering suggests the affinity of CTZ for the nonpolar microenvironment, which was further supported by the peak-to-peak correlation of Fourier transform infrared (FTIR) analysis and fluorescence measurement. In addition, HPLC analysis showed that the in vitro permeation release of CTZ-μEG from rabbit skin in the ethanolic phosphate buffer (pH = 7.4) was significantly increased by >98% within 6.0 h. This indicates the sustained release of CTZ in μEBG and the improvement in transdermal therapeutic efficacy of CTZ over its traditional topical formulations.

Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling

“…Thereby, droplet size and viscosity are the main physical parameters with a direct impact on the drug release. A high level of the aqueous phase and the nanometer scale of the dispersed droplets sustain a faster diffusion, as previously described for microemulsions with clotrimazole [ 111 ]. Reduced droplet diameters between 119.60–188.33 nm, specific for the ME 1–ME 4 fluid systems, were correlated to higher values of diffusion coefficients, while in the case of ME 5–ME 8 gel-like systems, elevated sizes up to 250.20 nm slowed down the MCZ release.…”

Natural Oils Enhance the Topical Delivery of Ketoconazole by Nanoemulgel for Fungal Infections

“…Despite enhancing permeation, the natural oils used in this study are nontoxic and moisturizing, prevent the loss of electrolytes and fluids, and maintain skin tonicity. The inadequate drug solubility, dissolution, and permeation led to poor flux from the pure ketoconazole gel . Shahid and colleagues developed a ketoconazole-loaded cationic nanoemulsion for topical delivery against cutaneous fungal infection.…”

“…The inadequate drug solubility, dissolution, and permeation led to poor flux from the pure ketoconazole gel. 46 Shahid and colleagues developed a ketoconazole-loaded cationic nanoemulsion for topical delivery against cutaneous fungal infection. The authors reported a nanoemulsion size of 239 nm and the highest drug permeation of 95.34 ± 1.22 μg cm –2 .…”

β-Caryophyllene-Loaded Microemulsion-Based Topical Hydrogel: A Promising Carrier to Enhance the Analgesic and Anti-Inflammatory Outcomes

“…Analogously, dilutions of Smix with saline were prepared and titrated with IPM until the end. All the percentage values of the three components for each titration were plotted on a ternary phase diagram to demarcate the homogeneous (microemulsion) [ 3 ] region from the heterogeneous phase [ 30 , 31 ]. Three compositions were selected out of the homogeneous phase of the pseudo-ternary diagram, accounting for almost the same amount of oil, but different Smix and saline amounts.…”