A Pharmaco-Technical Investigation of Thymoquinone and Peat-Sourced Fulvic Acid Nanoemulgel: A Combination Therapy

Abstract

Thymoquinone has a multitude of pharmacological effects and has been researched for a wide variety of indications, but with limited clinical success. It is associated with pharmaco-technical caveats such as hydrophobicity, high degradation, and a low oral bioavailability. A prudent approach warrants its usage through an alternative dermal route in combination with functional excipients to harness its potential for treating dermal afflictions, such as psoriasis. Henceforth, the present study explores a nanoformulation approach for designing a fulvic acid (peat-sourced)-based thymoquinone nanoemulsion gel (FTQ-NEG) for an enhanced solubility and improved absorption. The excipients, surfactant/co-surfactant, and oil selected for the o/w nanoemulsion (FTQ-NE) are Tween 80/Transcutol-P and kalonji oil. The formulation methodology includes high-energy ultrasonication complemented with a three-dimensional/factorial Box–Behnken design for guided optimization. The surface morphology assessment through scanning/transmission electron microscopy and fluorescence microscopy revealed a 100 nm spherical, globule-like structure of the prepared nanoemulsion. Furthermore, the optimized FTQ-NE had a zeta potential of −2.83 ± 0.14 Mv, refractive index of 1.415 ± 0.036, viscosity of 138.5 ± 3.08 mp, and pH of 5.8 ± 0.16, respectively. The optimized FTQ-NE was then formulated as a gel using Carbopol 971® (1%). The in vitro release analysis of the optimized FTQ-NEG showed a diffusion-dominant drug release (Higuchi model) for 48 h. The drug permeation flux observed for FTQ-NEG (3.64 μg/cm2/h) was much higher compared to that of the pure drug (1.77 mg/cm2/h). The results were further confirmed by confocal microscopy studies, which proved the improved penetration of thymoquinone through mice skin. Long-term stability studies of the purported formulation were also conducted and yielded satisfactory results.

Nanoemulsion Myricetin preparation increases the anticancer efficacy against Triple-negative Breast Cancer cells

“…Myr-NE preparation and optimization 2.2.1. Screening of components for NE preparation: Solubility and Miscibility studies: As discussed in an earlier publication [19][20], successful screening of various excipients (Oil, surfactants, and co-surfactants) was performed based on their drug solubility and miscibility ability, which is critical to the formulation development and management of a NE stability. Oils such as (Capryol 90, Castor oil, Labrafac Lipophile WL, Capmul MCM, Isopropyl myristate (IPM), Ethyl oleate, and Plurol oleique), surfactants (Kolliphor EL, Cremophor ELP, Labrasol, Tween 80, and Tween 20) and co-surfactants (Polyethylene glycol 200 (PEG)), Transcutol HP, Transcutol P, and Propylene glycol) were used for screening.…”

“…The data obtained from the titration procedure were used to construct pseudo-ternary phase diagrams. [19][20].…”

“…The required amount of Myricetin was first dissolved in a pre-selected oil; then, it was dissolved in a Smix. The obtained blend was then micro-titrated with double-distilled water [20]. Transparent formulations, evaluated by visual inspection, are taken for further thermodynamic stability studies.…”

“…DSC was performed for the analysis of melting point and solubilization, 2 mg sample of Myricetin, Myr-NE (lyophilized 5% w/v), and mannitol sample was sealed in an aluminum pan, and then the sample was allowed to heat at a temperature range of 100 -450 oC with a constant rate of 10 oC/m. At a flow rate of 60 ml per minute, nitrogen gas was purged to maintain an inert atmosphere [20].…”

Diosmin-Loaded Nanoemulsion-Based Gel Formulation: Development, Optimization, Wound Healing and Anti-Inflammatory Studies

“…Nanoemulsion (NEs) is a biphasic liquid dispersion in which the globule size ranges up to 100 nm. It is a thermodynamically stable isotropic system that contains oil, water, and an emulsifier, surfactant, and co-surfactant [24][25][26].…”