Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box–Behnken Design and In Vitro Evaluation

Abstract

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box–Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2–6 h). Optimization data in batches (F1–F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1–F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

Formulation-by-Design of Efinaconazole Spanlastic Nanovesicles for Transungual Delivery Using Statistical Risk Management and Multivariate Analytical Techniques

“…For a systematic exploration of these factors on the efinaconazole-loaded spanlastics, the number of individual factors was varied according to 2 3 full factorial designs, and the effects of these alterations in the factors were studied. The data were fitted to the first-order polynomial regression equation, as mentioned below: Y= b0 + b1X 1 + b2X 2 + b3X 3 + b12X 1 X 2 + b13X 1 X 3 + b23X 2 X 3 + b123X 1 X 2 X 3 (1) where, b0: the arithmetic mean of all the quantitative outcomes of the experimental runs, b1, b2, and b3: the coefficients calculated from the experimental values of Y for X 1 , X 2 , and X 3 , Xp Xq: p and q can be any number from 1, 2, and 3 indicating interaction. One factor along with its coefficients indicates the effect of that particular factor while the cross-product of two or more factors along its coefficients represents the interaction term among these factors.…”

“…Onychomycosis (tinea unguium) is a fungal infection of the nails of the toe or fingers. It usually affects all the components of the nail unit (matrix, nail-bed, or nail-plate) [ 1 ]. It usually causes pain, discomfort, and disfigurement, producing certain limitations for physical and occupational activities that may adversely affect quality of life [ 2 , 3 ].…”

Printing Drugs onto Nails for Effective Treatment of Onychomycosis

“…Unlike previous inkjet printing systems which printed onto different materials [21][22][23][24][25]69], this system allows for users to apply the drug directly onto the nail at the point of care. It also poses an advantage as it requires no additional steps [70]. However, in order for this to be translated into a real-world setting, there are a number of steps that need to be taken.…”

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

“…27 Iontophoresis has been evaluated in several studies which demonstrated improved permeation of the antifungal across the nail plate, confirming the results of in vitro and ex vivo fingernail and toenail models. 29,[32][33][34] Nair et al 35 showed that terbinafine hydrochloride, combined with PEG 400 as a chemical enhancer, applied for 6 h at 12 V showed increased nail plate permeation and drug release. Amichai et al and Samhan et al 17,36 reported studies with terbinafine hydrochloride in patients with toenail onychomycosis demonstrating effectiveness and safety of 4 weeks of treatment.…”