Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives

Abstract

The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Ungual penetration enhancers (PEs) were screened based on the hydration enhancement effect to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel (P407: 27.32% w/w, ethanol: 3.18% w/w and TGA: 4.72% w/w), prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation

“…This phenomenon could be explained, at least in part, by the reversible gelling properties of P407. Increasing the P407 concentration can increase the viscosity via the complex physical entanglement, retarding drug diffusion and release from the polymeric matrix [ 29 ]. Taken together, the SD-F4 formulation was selected as the optimal SD formulation for MT-102.…”

Fabrication of Topical Pluronic Lecithin Organogel Containing Immunomodulatory Drug for Site-Specific Drug Delivery

“…Poloxamer shows swelling behavior with increase in temperature and convert to gel at defined temperature which was noted as Gel Transition Temperature. 15…”

Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis

“…Hydrogels and in situ gels are used to overcome the low viscosity limitation of emulsions. Hydrogels can be prepared from synthetic or natural biomaterials or polymers and consist of a hydrophilic cross‐linked network capable of holding large quantities of water 52 . They are viscous and can be retained on the nail plate for longer periods of time, increasing application intervals and the sustained release of drugs.…”

“…Hydrogels can be prepared from synthetic or natural biomaterials or polymers and consist of a hydrophilic cross-linked network capable of holding large quantities of water. 52 They are viscous and can be retained on the nail plate for longer periods of time, increasing application intervals and the sustained release of drugs. In situ gels or self-assembling gels, on the contrary, are prepared in liquid They transition into a semi-solid state after their application onto the nail plate due to changes in concentration (by evaporation of water or solvent), pH or temperature.…”