to quantify the amount of drug present on the subjects’ backs.20 Plaum et al found that naftifine was present on all tape strip samples collected over the 28-day period after the cream or gel’s initial application.20 Moreover, the most relevant, deeper tape strip sets showed the potentially clinically relevant presence
of naftifine in the skin 28 days post-treatment.20 The investigators’ findings elucidate the progressive improvement in clinical and mycological response rates not only during the treatment period but also for up to four weeks post-treatment using naftifine cream or gel.20
Kircik and Onumah conducted an 8-week pilot study that examined
the efficacy of naftifine hydrochloride cream 2% and urea cream 39% for the treatment of tinea pedis with hyperkeratosis.
21 The treatment of tinea pedis with hyperkeratosis has traditionally been difficult for dermatologists due to the presence
of thick scaling after the resolution of the active fungal infection. So the investigators utilized urea, because it is a keratolytic
agent that clears the skin of hyperkeratosis scaling.21The investigators followed 10 patients for 8 weeks.21 At baseline, the subjects were given a 2-week supply of naftifine hydrochloride cream 2% and an 8-week supply of urea cream 39%.21 At weeks, 2, 4, and 8, the subjects were evaluated for compliance, and they also completed a visual analog scale (VAS) for pruritus severity and a dermatology life quality index (DLQI) questionnaire
in addition to verbal and clinical assessments.21 At week 8, Kircik and Onumah recorded significant clinical improvements and also subject satisfaction.21 Over the 8-week period, the subjects had a 1-point improvement in the resolution of their hyperkeratosis.21 Moreover, the subjects experienced a statistically
significant median 2-point improvement in VAS pruritus severity, and a median 3-point improvement over the 8 weeks in their DLQI from baseline.21 The investigators concluded that naftifine hydrochloride cream 2% and urea cream 39% were effective for the treatment of tinea pedis with hyperkeratosis, because, in part, the urea cream mitigated hyperkeratotic scaling,
which facilitated the penetration of naftifine hydrochloride.
A 2014 study, conducted by Erdal et al, assessed the absorption of another, allylamine , terbinafine in a gel formulation in the presence and absence of three chemical enhancers: nerolidol, dl-limonene, and urea.25 The investigators applied terbinafine 1% to the SC of healthy subjects, and, after 8 hours, used tape stripping and ATR-FTIR spectroscopy to determine absorption rates.25 Erdal et al found that the terbinafine gel formulation containing nerolidol produced significantly greater terbinafine permeation through the SC than formulations containing urea and dl-limonene.25 ATR-FTIR spectroscopy demonstrated that the terbinafine gel formulation containing nerolidol induced lipid bilayer disruption in the SC.25 The formulation with urea produced enhanced permeation of terbinafine into the SC, whereas dl-limonene produced a relatively minimal accumulation
of terbinafine in the upper SC.25 Erdal et al concluded that
a terbinafine gel formulation with nerolidol could potentially be of benefit for both superficial and deep cutaneous fungal infections.
25
A study published in 2015, conducted by Pillai et al, assessed various formulations of butenafine hydrochloride gel, and their affects on ex vivo skin permeation and antifungal activity when compared to marketed butenafine hydrochloride cream.26 The investigators incorporated isopropyl palmitate for the oil phase, and aerosol OT and sorbitan monooleate as surfactants.26 They found that incorporating the aforementioned ingredients into Carbopol 940 gel had greater efficacy when compared to sodium
alginate or hydroxyl propyl methyl cellulose gels. Pillai et al concluded that the developed gel demonstrated superior ex vivo skin permeation and antifungal activity when compared to marketed butenafine hydrochloride cream.26
Several studies have evaluated the safety and efficacy of a formulation of luliconazole cream 1%, which contains benzyl alcohol, butylated hydroxytoluene, cetostearyl alcohol, isopropyl
myristate, medium-chain triglycerides methylparaben, polysorbate 60, propylene glycol, purified water, and sorbitan monostearate. Benzyl alchohol, propylene glycol, and isopropyl myristate act as the vehicle’s primary penetration enhancers. In the preclinical guinea pig studies, high levels of luliconazole were achieved in the stratum corneum of guinea pig plantar skin within three consecutive days of application and was maintained
over 14 days of application.27
A phase III randomized, double-blind, vehicle-controlled study assessed the safety and efficacy of luliconazole cream 1% in subjects with tinea pedis who were 12 years of and older.28 The study included 321 patients; 159 subjects were randomized to receive luliconazole cream 1% and 162 received the vehicle once daily for 14 days.28 The efficacy of luliconazole cream 1% regarding
erythema, scaling, pruritus and mycology was evaluated at days 28 and 42, which were 14 and 28 days post-treatment.28 On day 42, investigators found that 26.4% of subjects receiving
luliconazole cream 1% achieved a complete clearance of clinical signs and mycology, and 1.9% of patients treated with the vehicle achieved a complete clearance of clinical signs and mycology (P< 0.001)28Comparable safety profiles were also recorded
for luliconazole cream and the vehicle.
Sertaconazole has shown efficacious antifungal activity against dermatophytes that may have reduced susceptibility to other azoles. Susilo et al conducted a study to assess the rate and extent of the penetration of sertaconazole nitrate 2% cream into the SC.29 The study included 12 healthy volunteers who were exposed to 8 applications of sertaconazole nitrate 2% cream or placebo over time intervals ranging between 0 and 48 hours.29 The investigators used tape stripping and an HPLC-assay to determine
the penetration of sertaconazole into three layers of the
