Sertaconazole

Therapeutic importance of synthetic thiophene.[Pubmed:30564984]

Chem Cent J. 2018 Dec 19;12(1):137.

Thiophene and its substituted derivatives are very important class of heterocyclic compounds which shows interesting applications in the field of medicinal chemistry. It has made an indispensable anchor for medicinal chemists to produce combinatorial library and carry out exhaustive efforts in the search of lead molecules. It has been reported to possess a wide range of therapeutic properties with diverse applications in medicinal chemistry and material science, attracting great interest in industry as well as academia. It has been proven to be effectual drugs in present respective disease scenario. They are remarkably effective compounds both with respect to their biological and physiological functions such as anti-inflammatory, anti-psychotic, anti-arrhythmic, anti-anxiety, anti-fungal, antioxidant, estrogen receptor modulating, anti-mitotic, anti-microbial, kinases inhibiting and anti-cancer. Thus the synthesis and characterization of novel thiophene moieties with wider therapeutic activity is a topic of interest for the medicinal chemist to synthesize and investigate new structural prototypes with more effective pharmacological activity. However, several commercially available drugs such as Tipepidine, Tiquizium Bromides, Timepidium Bromide, Dorzolamide, Tioconazole, Citizolam, Sertaconazole Nitrate and Benocyclidine also contain thiophene nucleus. Therefore, it seems to be a requirement to collect recent information in order to understand the current status of the thiophene nucleus in medicinal chemistry research.

Solutol HS15 based binary mixed micelles with penetration enhancers for augmented corneal delivery of sertaconazole nitrate: optimization, in vitro, ex vivo and in vivo characterization.[Pubmed:30442039]

Drug Deliv. 2018 Nov;25(1):1706-1717.

Keratomycosis is a serious corneal disease that can cause a permanent visual disability if not treated effectively. Sertaconazole nitrate (STZ), a novel broad spectrum antifungal drug, was suggested as a promising treatment. However, its utility in the ocular route is restricted by its poor solubility, along with other problems facing the ocular delivery like short residence time, and the existing corneal barrier. Therefore, the objective of this study was to formulate STZ loaded binary mixed micelles (STZ-MMs) enriched with different penetration enhancers using thin-film hydration method, based on a 3(1).2(2) mixed factorial design. Different formulation variables were examined, namely, type of auxiliary surfactant, type of penetration enhancer, and total surfactants: drug ratio, and their effects on the solubility of STZ in MMs (SM), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) were evaluated. STZ-MMs enhanced STZ aqueous solubility up to 338.82-fold compared to free STZ. Two optimized formulations (MM-8 and MM-11) based on the desirability factor (0.891 and 0.866) were selected by Design expert((R)) software for further investigations. The optimized formulations were imaged by TEM which revealed nanosized spherical micelles. Moreover, they were examined for corneal mucoadhesion, stability upon dilution, storage effect, and ex vivo corneal permeation studies. Finally, both in vivo corneal uptake and in vivo corneal tolerance were investigated. MM-8 showed superiority in the ex vivo and in vivo permeation studies when compared to the STZ-suspension. The obtained results suggest that the aforementioned STZ loaded mixed micellar system could be an effective candidate for Keratomycosis-targeted therapy.

A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis.[Pubmed:30409926]

Indian J Dermatol Venereol Leprol. 2018 Nov 5. pii: 245052.

Background: Dermatophytosis is becoming increasingly unresponsive to conventional antifungals. Newer topical antifungals may be more effective in these patients. Aims: To evaluate and compare the efficacy and safety of amorolfine 0.25% cream and Sertaconazole 2% cream in limited tinea cruris/corporis. Methods: A single-center, randomized (1:1), double-blind, parallel group, active-controlled trial (CTRI/2014/12/005246) was performed. Sixty-six untreated adults with acutely symptomatic tinea cruris/corporis were included in the study. All patients had limited cutaneous involvement and were KOH mount positive. Group A received amorolfine 0.25% cream, and group B received Sertaconazole 2% cream twice daily application to the lesions for 4 weeks. After the baseline visit, four follow-up visits were carried out. The outcome measures for effectiveness were clinical and mycological cure. Safety parameters studied were treatment-emergent adverse events and changes in routine laboratory parameters. Results: Both Sertaconazole and amorolfine significantly reduced symptoms (P < 0.001) in both groups. However, improvement in symptoms (pruritus, burning sensation, erythema, scaling and crusting) was significantly greater in the Sertaconazole group at every follow-up visit. Sertaconazole cream was also more effective than amorolfine cream in reducing the number of lesions (P = 0.002 at 12 weeks) and improving the Dermatology Life Quality Index (P < 0.001) at all the follow-up visits. Adverse events were similar in the two groups (P = 0.117). Fungal cultures became negative in 92.3% of the Sertaconazole group as compared to 80% in the amorolfine group (P = 0.010). Limitations: Antifungal susceptibility testing could not be done. Conclusion: Sertaconazole 2% is superior to amorolfine 0.25%, both in terms of effectiveness and tolerability. Improvement can be appreciated from second week onwards.

Corneal targeted Sertaconazole nitrate loaded cubosomes: Preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies.[Pubmed:30393167]

Int J Pharm. 2018 Dec 20;553(1-2):386-397.

Sertaconazole nitrate (STZ) is a poorly soluble antifungal drug commonly used for treating fungal skin infections. Introducing it as a new treatment option for the management of fungal keratitis, requires the development of a delivery system capable of targeting the infected cornea with an adequate STZ concentration. Hence, Sertaconazole nitrate loaded cubosomes (STZ-CUBs) were prepared, characterized and optimized based on a 3(3) central composite face-centred design. Optimized formulation (CUB-opt) showed maximum desirability (0.905), with solubilization efficiency (SE%) of 94.50+/-0.51%, particle size (PS) of 216.55+/-2.33nm, polydispersity index (PDI) of 0.229+/-0.11 and zeta potential (ZP) of 34.00+/-6.93mV. Under the transmission electron microscope, it showed discrete cubic shaped structures. Moreover, it exhibited a promising mucoadhesive behavior, terminal sterilization stability, and storage stability. Ex vivo corneal permeation study revealed its ability to enhance the steady state flux (Jss) and the permeability coefficient (KP) of STZ, compared to STZ-suspension. Finally, CUB-opt formulation was found to be safe on the corneal tissues in the in vivo corneal tolerance study, and demonstrated a superior corneal penetration power in the in vivo corneal uptake study.

Sertaconazole nitrate loaded nanovesicular systems for targeting skin fungal infection: In-vitro, ex-vivo and in-vivo evaluation.[Pubmed:28522423]

Int J Pharm. 2017 Jul 15;527(1-2):1-11.

The aim of this study was to develop different vesicular systems for Sertaconazole nitrate and evaluate the ability of targeting deep skin layers to treat dermal fungal infection. Therefore, different phospholipid based nanovesicles, namely liposomes, glycerosomes, transferosmes and ethosomes were prepared and in-vitro evaluated for morphology, entrapment efficiency, vesicle size and zeta potential value, followed by ex-vivo evaluation through skin penetration and permeation. The selected vesicular formula was incorporated into gel base system and assessed by ex-vivo permeation visualization study using confocal laser scanning microscopy (CLSM). In-vivo study was performed to compare antifungal efficacy of STZL loaded vesicular gel with commercial cream (Dermofix((R))). All nanovesicles were unilamller and almost spherical in shape. Entrapment efficiency, vesicle size and zeta potential were dependent upon vesicle composition. Vesicular formulae promoted drug permeation compared to commercial cream where transferosomal system containing 3% soyphospholipid (SPC) and 0.15% sodium deoxychloate (SDC) exhibited highest flux (645mug/cm(2)/h). The CLSM images confirmed the penetration of the developed probe-loaded tansferosomal system to viable epidermis layers with fluorescence intensity greater than unencapsulated probe. The in-vivo study revealed significant prevention effect in immunecompromised rat model. Furthermore, the antifungal activity with lowest histopathological changes was significantly observed in the developed STZL-loaded transferosomal gel compared to commercial cream using immunecompromised rat model with fungal skin infection.