Sertaconazole Research Articles

An Experimentally Designed Sertaconazole Sensor for Selective and Enhanced Potentiometric Response: Determination in Cream, Plasma & in Presence of Other Imidazoles

AbstractA two‐step experimental design was followed to develop a potentiometric solid contact ion‐selective electrode for sertaconazole (STN) determination. A full factorial design was first employed in screening for the best cation exchanger, ionophore and conducting polymer. Amounts of the selected cation exchanger; tetrakis[3,5‐bis(trifluoromethyl)phenyl] borate (TFPB), and ionophore; calix[6]arene (CX6), incorporated in STN sensing membrane were then optimized with the aid of face centered composite design. Calibration slope, detection limit and electrode selectivity in presence of another imidazole‐classified drug; econazole, were the selected responses in both designs. The optimized ion‐sensing membrane, containing 1.0 mg TFPB and 9.9 mg CX6, showed enhanced responses compared to the primarily screened ones. This optimized electrode exhibited a linear response over a concentration range of 1.0×10−6‐−1.0×10−3 M with a Nernstian slope of 57.50 mV/decade. The detection limit was lowered by about one order of magnitude via this optimization to equal 3.16×10−7 M. The proposed electrode was successfully challenged for STN determination in the presence of other imidazoles. It was then used for STN determination in cream and spiked plasma as an example of biological fluid. Our proposed potentiometric method was finally compared to the reported chromatographic ones in terms of sensitivity, and greenness evaluation by the widely applicable Analytical GREEnness (AGREE) tool. The comparison revealed the superiority of our method in terms of sensitivity and sustainability.

Evaluation of the effectiveness of topical use of sertaconazole in dermatophytosis

Objective — to evaluate the effectiveness of a cream containing sertaconazole nitrate 2 % (Onabet 2 % cream) in patients with various forms of dermatophytosis. Materials and methods. 32 patients aged 21—50 were under outpatient observation. The duration of dermatophytosis varied from several weeks to 3 months. Tinea corporis was diagnosed in 25.0 % of patients, foot mycosis in 43.8 %, and axillary mycosis in 31.2 %. The diagnosis was based on the clinical manifestations of the disease and the results of microscopic examination with potassium hydroxide (PH). The clinical picture was evaluated based on the presence of subjective and objective signs (itching, erythema, scaling, vesicles/maceration, pustules) and their intensity according to the scale: 0 points — absence, 1 point — mild, 2 points — moderate, 3 points — severe. The area of skin damage was determined using the «rule of the palm» in patients. The final score of clinical manifestations was calculated by adding the individual scores of each symptom and the value of the area of the affected skin. Onabet 2 % cream was applied by patients twice a day to the affected area of the skin for 4 weeks. Results and discussion. As a result of topical treatment, positive dynamics regarding the clinical manifestations of dermatophytosis were noted in all patients. The regression of inflammatory symptoms (itching, erythema, wetting in 65.5, 40.6 and 71.4 % of patients, respectively) by the end of the 1st week of treatment serves as evidence of anti-fungal, anti-inflammatory and anti-pruritic effects. The terms of regression of clinical manifestations of dermatophytosis depended on the clinical form of the infection. Clinical remission by the end of the 1st week of therapy in 34.4 % of patients, clinical remission and mycological negativity by the end of the 2nd week in 81.3 % of patients testify to the rapid effect of the drug. At the end of the 6th week, clinical success was achieved in 93.7 %, mycological (pathogen eradication) in 100.0 % of patients. Remote observation results within 3 months showed no disease recurrence in all patients. Side effects during treatment were not registered. Conclusions. Onabet cream 2 % is a modern topical antimycotic with a wide spectrum of action; its use twice a day for 1 month allows for achieving clinical cure in 93.7 %, etiological cure in 100 % of patients with dermatophytes (tinea corporis, tinea pedis, and tinea cruris). The high effectiveness and safety of Onabet cream in treating dermatophytosis allow us to recommend this topical agent for treating patients with dermatophytosis.

Sertaconazole-PLGA nanoparticles for management of ocular keratitis

Ocular fungal infections can pose severe health conditions that may develop into vision impairment and blindness. Sertaconazole (STZ) is a widely used antifungal; however, its low aqueous solubility restricts its topical application for managing ocular keratitis. This investigation aimed to develop polymeric nanoparticles as delivery carriers to improve the ophthalmic availability of STZ for treating fungal keratitis. The impact of STZ solid dispersion incorporation within polymeric nanoparticles for in vitro drug release enhancement was also evaluated. STZ-laden PLGA NPs were formulated via nanoprecipitation technology, using a 24-full factorial layout to optimize the formulation. The formed nanoparticles were assessed for encapsulation efficiency percentage, hydrodynamic size, surface charge, and polydispersity index. The selected formula exhibited a particle size of 305.9 ± 4.36 nm, an entrapment efficiency (EE%) of 98.8 ± 0.008%, a surface charge of 22.57 ± 0.23 mV, and a low polydispersity index, indicating a uniform size distribution. Incorporating STZ in a solid dispersion form with PEG 2000 at a 1:3 w/w drug-to-carrier ratio increased the hydrodynamic size of the PLGA NPs. However, no significant variation in the entrapment efficiency percentage was recorded. The developed STZ-solid dispersion-loaded PLGA NPs have round-shaped structures. DSC and FTIR spectroscopy data indicated drug amorphization with successful loading within the PLGA matrix. Introducing the drug as a solid dispersion within PLGA NPs resulted in enhancing the rate of drug dissolution at initial time intervals, followed by a controlled drug release over 24 h. STZ-PEG2000-laden PLGA NPs enhanced permeability through rabbits’ corneas (Papp), 2.5-fold higher versus STZ-loaded PLGA NPs. The antimycotic activity of the developed formulation was tested against Candida albicans, and a 4-fold reduction in the MIC value was detected upon applying the nanoparticles’ formulation embedding STZ solid dispersion versus that containing the free drug. In conclusion, the formulation of solid dispersions of STZ loaded in PLGA nanoparticles may serve as a starting point for an efficient approach to the ocular delivery of hydrophobic medications and a viable setup for the upcoming research in animal models of fungal keratitis.

Formulation of Lipid Nanoparticles based Nanogel of Sertaconazole Nitrate and its Evaluation

Background: Sertaconazole nitrate is a topical antifungal drug used to treat interdigital tinea pedis in patients with immunocompetent conditions. The class of imidazole includes the antifungal medication sertaconazole nitrate. It is available in topical formulations for treating skin infections, including athlete's foot. Solid lipid nanoparticles (SLN) are at the cutting edge of nanotechnology, with several potential uses in drug delivery and research. Because of their unique size-dependent features, lipid nanoparticles hold the promise of novel therapies. Objective: Drug incorporation into nanocarriers creates a new drug delivery prototype that could be employed for drug targeting. The research aims to study the formulation and evaluation of Sertaconazole nitrate solid lipid nanoparticles. The goal behind formulating SLN gel is to provide and maintain therapeutic concentrations of the drug at the target biological site to maximise therapeutic efficacy and minimise side effects. Methods: Sertaconazole Nitrate Solid Lipid Nanoparticles are prepared by using High Pressure Homogenizer to get nanogel formulation as the final formulation and In-vitro drug release using a diffusion apparatus. The prepared SLNs were evaluated in their FTIR studies to determine compatibility between the drug and the excipients; zeta potential indicates the solid lipid nanoparticle was stable, and polydispersity index was used to determine particle size. Result: The results demonstrate that optimised SLN-based Sertaconazole nitrate gel exhibited the best physicochemical properties, including FTIR studies of the drug, excipients, and optimised formulation demonstrate that all are compatible with each other, particle size is less than 200 nm, zeta potential ranging from 12 to -20 mV, and highest entrapment efficiency is 71.48%. Optimised solid lipid nanoparticles showed good in vitro release and antimicrobial results. The main application of SLN large scale-up is possible, and the drug can be effective with less dose incor-poration. Conclusion: In this research work, the proposed plan of work SLN of Sertaconazole Nitrate was formulated successfully. The preliminary identification tests were performed, such as melting point determination, estimation of λmax by UV-visible spectrophotometry and plot of its calibration curve in solvent and buffer system, and FT-IR investigation to confirm the purity and confirmation of medication. High physical stability and drug loading are advantageous to SLN.

Possibilities of local therapy of recurrent candidiasis against the background of mixed vaginal dysbiosis

Introduction. The article describes the experience of treating patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using a variant of complex local therapy with drugs containing sertaconazole nitrate and benzyl-dimethyl-[3-(myristoylamino) propyl] ammonium chloride monohydrate.Aim. To evaluate the efficacy of local therapy in patients with recurrent vulvovaginal candidosis with underlying mixed non-specific vaginal dysbiosis.Materials and methods. A prospective open randomized clinical trial to evaluate the outcomes of treatment with drugs containing sertaconazole nitrate at a dose of 300 mg (Flucovag®, vaginal suppositories, two times with an interval of 7 days) and benzyl-dimethyl-[3-(myristoylamino)propyl] ammonium chloride monohydrate at a dose of 15 mg (Miramistin® vaginal suppositories once a day at bedtime for 10 days) in women with mixed nonspecific infectious vaginal diseases with underlying recurrent vulvovaginal candidosis (n = 68) was conducted. Methods: vaginal microbiota evaluation with AmpliPrime® Florocenosis/Bacterial vaginosis-FL PCR (NextBio LLC, Russian Federation), vaginal pH, Hay/Ison scoring criteria, antimycotic sensitivity evaluation against Candida spp. (NCCLS standards).Results and discussion. This kind of local complex therapy in patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using drugs containing sertaconazole nitrate (Flucovag®) and benzyl-dimethyl[3-(myristoylamino) propyl]ammonium chloride monohydrate (Miramistin®), followed by probiotic contamination showed high clinical (94.1 ± 2.3%) and microbiological (81.9 ± 2.1%) efficacy combined with safety and satisfactory compliance.Conclusion. A comprehensive approach to the treatment of mixed nonspecific vaginal dysbiosis with underlying recurrent vulvovaginal candidosis showed high clinical efficacy and satisfactory compliance.

Serum levels of tumor necrosis factor (TNF-α) and vaginal gene expression of toll-like receptor 2 (TLR2) & microtubule-associated protein 1 light chain 3 (LC3) after treatment of vulvovaginal candidiasis with sertaconazole nitrate spanlastics

The irritating infection known as vulvovaginal candidiasis (VVC) affects women all over the world. Around 75% of women will acquire at least one attack throughout their lives. In addition to its demonstrated antifungal properties, sertaconazole nitrate (SCN) also exhibits anti-inflammatory effects, which are of significant importance in the therapeutic management of (VVC). Despite its benefits, SCN suffers from poor solubility, which affects its biological activity. This project's objective is to construct SCN spanlstics in order to enhance its solubility as well as its antifungal and anti-inflammatory activities. SCN spanlastics were created utilizing the ethanol injection technique, after which they were characterized. Chitosan (2.5%) w/w gels containing 2 % w/w of SCN in the form of spanlastics were prepared, and then the in vitro antifungal activity of the prepared chitosan gel and commercial SCN cream (Dermofix) was performed. After a complete gynecological examination, vaginal swabs were obtained from patients suspected of VVC and then cultured on Sabouraud dextrose agar for phenotypic identification. VVC was then induced in nonpregnant ovariectomized female rats using isolated and identified Candida albicans (C. albicans) species. In order to detect the difference between chitosan gel containing SCN spanlastics and the commercial (Dermofix) cream, serum levels of pro-inflammatory cytokine Tumor necrosis factor (TNF- α) were detected. After sacrificing the rats, gene expression of toll-like receptor 2 (TLR2) & microtubule-associated protein 1 light chain 3 (LC3) in vaginal tissue and immunohistochemical expression of interleukin-6 (IL-6) as an inflammatory chemokine were performed in all groups. Results revealed that SCN was successfully entrapped into spanlastics, the particle size ranged from 1.6 ± 0.050 to 5.7 ± 0.900 μm in diameter; in-vitro dissolution of SCN was significantly enhanced from chitosan gel compared to that from Dermofix cream, the inhibition zone of prepared chitosan gel containing SCN spanlastics was significantly larger compared to that of Dermofix cream. Our results revealed that the anti-inflammatory effect of SCN in the form of spanlastics was significantly greater than that of commercial (Dermofix) cream. Finally, we recommend the use of SCN spanlastics as the best antifungal and anti-inflammatory formulation in cases of vaginal candidiasis.

Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery

BackgroundLung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency.MethodsNanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo.ResultsOur nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects.ConclusionsOur results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.

Design and Development of Sertaconazole Nitrate Loaded Silver Nanoparticulate Mucoadhesive Tablets for the Treatment of Vaginal Candidiasis

Vaginal candidiasis, a fungal infection estimates that 75 % of women will be suffering at least once during their lifetime. The disorders of this infection might be premature birth, pelvic inflammation, abortion, the transmission of sexual disorders, etc. In the present research, mucoadhesive vaginal tablets containing sertaconazole nitrate-loaded silver nanoparticles formulations were developed which increases the proximity period of the medicine with the vaginal mucosa, showing sustained drug release. The drug-loaded silver nanoparticle was synthesized by the chemical reduction method. There was successful conjugation of sertaconazole nitrate with silver nanoparticles (Ser-AgNP1) therefore, the drug’s solubility is increased by 2.51 folds. The confirmation of silver nanoparticles was accessed by UV-visible spectroscopy. The mucoadhesive vaginal tablets were formulated and evaluated for swelling index, mucoadhesive force, residence time, In vitro dissolution and release kinetics, stability, and antifungal study. Optimized batch F8 was selected based on optimum mucoadhesive force (2.59±0.25N), % swelling index (86.50±0.11%), and sustained drug release (95.63±0.16%) up to 12 hr and showed greater antifungal activity. Overall study reveals that a prepared novel formulation, a mucoadhesive vaginal tablet containing sertaconazole nitrate loaded silver nanoparticles prevail over sertaconazole nitrate poor solubility and delivered drug during an extended period of time and also improved antifungal activity against Candida albicans.

Chiral Analysis of Sertaconazole by HPLC Method on Polysaccharide Derivatives

Sertaconazole is a pharmaceutical product in the form of a cream, gel, powder, and solution for dermatological use and vaginal cream, tablets, and ovules for gynecological use. The active ingredient is 2% sertaconazole nitrate. Sertaconazole nitrate is an azole antifungal agent, with notable antifungal activity. The active principal structure of sertaconazole has an asymmetric carbon, which makes this molecule chiral and it is in the form of an enantiomeric mixture. Currently, the control of drugs is based on qualitative and quantitative analysis by the use of effective analytical methods for chiral active ingredients. The enantiomeric separation of an antifungal compound, Sertaconazole, using HPLC is described in this work. The columns employed were based on polysaccharide derivatives (Chiralpak IB, Chiralcel OD-H), and the results show that the separations obtained are better, in terms of high resolution and short analysis time. Chiral separation of Sertaconazole was explained by hydrogen bondings and π-π interactions, between the CSP and this antifungal agent.

Sertaconazole nitrate targets IDO1 and regulates the MAPK signaling pathway to induce autophagy and apoptosis in CRC cells

Colorectal cancer (CRC) has become the third most frequently occurring malignant tumor worldwide. It is vital to identify novel, effective targeted treatments while considering side effects and drug resistance in the clinic. Recently, the tryptophan-metabolizing enzyme indole-2, 3-dioxygenase 1 (IDO1) has been widely reported to be overexpressed in CRC, indicating that blocking IDO1 with small-molecule inhibitors may be a promising approach to CRC treatment. In this study, the antifungal drug sertaconazole nitrate (STZ) was repurposed and showed antitumor activity, and therefore, its anticancer effect was further investigated in CRC cells. The SwissTargetPrediction analysis indicated that STZ binding to IDO1 was significantly and highly probable, and STZ was found to downregulate IDO1 in CRC cells in a dose-dependent manner. STZ exhibited considerable antiproliferative activity and induced apoptosis and autophagy in HCT116 and RKO cells. Moreover, based on an RNA-seq analysis, STZ was shown to regulate signal transducer and activator of transcription 3 (STAT3) and the mitogen-activated protein kinase (MAPK) signaling pathways. We discovered that STZ suppressed tumor growth in an HCT116 nude mouse xenograft tumor model without causing evident cytotoxicity. In conclusion, our results reveal that STZ induces antitumor effects in CRC by inhibiting IDO1-modulated autophagy and apoptosis, providing a clue for repurposing STZ as a novel and potentially effective candidate medication for the future treatment of CRC.

Sertaconazole-Nitrate-Loaded Leciplex for Treating Keratomycosis: Optimization Using D-Optimal Design and In Vitro, Ex Vivo, and In Vivo Studies.

This study aims to develop efficient topical therapy for keratomycosis using sertaconazolenitrate (STZN)-loaded leciplex (LP). The D-optimal design was used to optimize STZN-loaded LP by utilizing soy phosphatidylcholine (SPC) molar ratio (X1), cationic surfactant molar ratio (X2), and cationic surfactant type (X3) as the independent variables, whereas their impact was studied for entrapment efficiency percent (EE; Y1), particle size (PS; Y2), polydispersity index (PDI; Y3), zeta potential (ZP; Y4), and permeability coefficient (Kp; Y5). The optimized formula was evaluated regarding morphology, ex vivo permeation, mucoadhesion, stability, and in vivo studies. The optimized formula was spherical and showed EE of 84.87 ± 1.71%, PS of 39.70 ± 1.35 nm, PDI of 0.242 ± 0.006, ZP of +54.60 ± 0.24 mV, and Kp of 0.0577 ± 0.0001 cm/h. The ex vivo permeation study revealed that the optimized formula enhanced the Kp and corneal deposition by 2.78 and 12.49 folds, respectively, compared to the aqueous drug dispersion. Furthermore, the optimized formula was stable and revealed promising mucoadhesion properties. Finally, the in vivo studies showed that the optimized formula was superior to the drug dispersion in treating rats with induced keratomycosis. These results confirmed the capabilities of LP as a promising nanocarrier for treating ocular diseases topically.

In Situ Swelling Formulation of Glycerol-Monooleate-Derived Lyotropic Liquid Crystals Proposed for Local Vaginal Application.

Hydrogels have been extensively investigated to identify innovative formulations that can fulfill all the necessary purposes to improve local vaginal therapy through the mucosa. Herein, we propose in situ-forming lyotropic liquid crystals (LLCs) derived from a cheap and GRAS (generally recognized as safe) ingredient as an intravaginal delivery system. The system consists of a precursor solution loaded with sertaconazole nitrate as a model drug, which is able to easily swell in a stable three-dimensional structure by absorbing simulated vaginal fluid. Under polarized light microscopy the precursor solution and the formed phase of LLCs showed the typical textures belonging to anisotropic and an isotropic mesophases, respectively. A deep rheological investigation by Kinexus® Pro proved the stability and strength of the cubic phase, as well as its potential in mucoadhesion. In vitro degradation studies showed a slow matrix erosion, consistent with data obtained from lipophilic drug release studies in simulated vaginal fluid. Therefore, the suggested cubic phase based on lyotropic liquid crystals could represent a valid proposal as a vaginal drug delivery system due to its characteristics of resistance, adhesion and the possibility of providing a slow and controlled release of drugs directly at the administration site.

A Meta-Analysis on the Effectiveness of Sertaconazole 2% Cream Compared with Other Topical Therapies for Seborrheic Dermatitis.

Seborrheic dermatitis (SD) is a relapsing inflammatory skin disorder that affects the seborrheic areas of the body. Its etiology is not completely elucidated; however, the link between disease exacerbations and the proliferation of Malassezia spp., along with the good response to antifungal agents, indicate the role of fungi in its pathophysiology. Sertaconazole nitrate is a relatively new imidazole antifungal agent with a particular structure, consisting in a benzothiophene ring similar to the indole ring of tryptophan, and it acts mainly through the inhibition of ergosterol synthesis and the formation of pores in the fungal cell membrane. The aim of our study was to evaluate the efficiency of sertaconazole 2% cream compared with other topical treatments in patients with SD. We performed an extensive literature search by browsing the PubMed database with the keyword combination “sertaconazole AND seborrheic dermatitis AND clinical trial”, which retrieved eight controlled clinical trials evaluating the effects of sertaconazole in SD. All of the clinical trials included a standard scoring index (SI). At 28 days since the beginning of the treatment, the sertaconazole regimen was associated with a significantly higher percentage of patients with mild SI and a lower percentage of patients with moderate or severe SI (odds ratio 0.51) than the other investigated treatments—hydrocortisone, ketoconazole, clotrimazole, metronidazole, pimecrolimus, and tacrolimus (odds ratio 1.95). In conclusion, treatment with sertaconazole 2% cream may represent an efficient alternative therapy for patients with SD.

MICROBIOLOGICAL ANALYTICAL METHOD FOR DETERMINATION OF SERTACONAZOLE NITRATE IN PHARMACEUTICAL FORMULATIONS

Sertaconazole nitrate is a third generation synthetic broad-spectrum, benzothiophene imidazole antifungal agent. A new microbiological method was developed for analysis of sertaconazole tablets using candida Albicans as test microorganism. The diffusion assay method was optimized by using different media, organisms and conditions. Prospective validation of the method showed adequate linearity (r = 0.9964), precision (% RSD<2%) and accuracy (mean recovery = 98.26%). Highperformance liquid chromatography was chosen as a comparison method for voriconazole determination. Results of both the microbiological and HPLC methods were compared with student ttest and the contents of voriconazole determined by both methods, showed a strong correlation. Highperformance liquid chromatography was chosen as a comparison method. Results of both the microbiological and HPLC methods were compared with student t-test and the contents of sertaconazole determined by both methods showed a strong correlation. The microbiological analytical method which was developed gives true indication of biological activity and can be used for routine quality control analysis of sertaconazole nitrate in dosage forms. Key words: Sertaconazole nitrate, t-test, Candida albicans, Diffusion method, HPLC, Method validation.

Augmented local skin accumulation efficiency of sertaconazole nitrate via glycerosomal hydrogel: Formulation, statistical optimization, ex vivo performance and in vivo penetration

This study aimed at formulating Sertaconazole nitrate (SZ), in a suitable glycerosomes based topical formulation that offers deep skin penetration and high local skin accumulation efficiency. SZ Glycerosomes were prepared using thin-film hydration technique according to a 24 full factorial design. Studied factors were Phosphatidylcholine (PhC) amount, Brij® L4: PhC ratio, glycerol concentration, and method of further treatment either sonication or freezing and thawing. The power of the design for each response was calculated before design implementation. Suitable models were elucidated for studied responses and their validity was checked. An optimized formula (O-GL) was numerically optimized using Design expert software®. The O-GL had suitable characterization with entrapment efficiency of 80.6 ± 2.9%, particle size of 418 ± 11 nm, polydispersity index of 0.452 ± 0.27, and zeta potential of −52.6 ± 0.6 mV. This O-GL was incorporated in a hydrogel (O-GL hydrogel). This O-GL hydrogel showed superior ex-vivo deposition in rat skin (Local accumulation efficiency: 55.1 ± 7.9) compared to O-GL (14.9 ± 1.1) and Dermofix® cream (marketed product) (13.1 ± 0.8). It also showed deep in-vivo penetration that reached deep dermal skin layers. Thus, the proposed formula (O-GL hydrogel) is promising for SZ topical delivery. It achieved deep skin penetration and high local skin accumulation efficiency for the effective treatment of fungal infections.

Efficacy of antifungal agents against fungal spores: An in vitro study using microplate laser nephelometry and an artificially infected 3D skin model.

Dermal fungal infections seem to have increased over recent years. There is further a shift from anthropophilic dermatophytes to a growing prevalence of zoophilic species and the emergence of resistant strains. New antifungals are needed to combat these fungi and their resting spores. This study aimed to investigate the sporicidal effects of sertaconazole nitrate using microplate laser nephelometry against the microconidia of Trichophyton, chlamydospores of Epidermophyton, blastospores of Candida, and conidia of the mold Scopulariopsis brevicaulis. The results obtained were compared with those from ciclopirox olamine and terbinafine. The sporicidal activity was further determined using infected three‐dimensional full skin models to determine the antifungal effects in the presence of human cells. Sertaconazole nitrate inhibited the growth of dermatophytes, molds, and yeasts. Ciclopirox olamine also had good antifungal activity, although higher concentrations were needed compared to sertaconazole nitrate. Terbinafine was highly effective against most dermatophytes, but higher concentrations were required to kill the resistant strain Trichophyton indotineae. Sertaconazole nitrate, ciclopirox olamine, and terbinafine had no negative effects on full skin models. Sertaconazole nitrate reduced the growth of fungal and yeast spores over 72 h. Ciclopirox olamine and terbinafine also inhibited the growth of dermatophytes and molds but had significantly lower effects on the yeast. Sertaconazole nitrate might have advantages over the commonly used antifungals ciclopirox olamine and terbinafine in combating resting spores, which persist in the tissues, and thus in the therapy of recurring dermatomycoses.

Development and comprehensive greenness assessment for MEKC and HPTLC methods for simultaneous estimation of sertaconazole with two co-formulated preservatives in pharmaceutical dosage forms

Four greenness assessment tools: National Environmental Methods Index (NEMI), Ecoscale Assessment (ESA), Green Analytical Procedure Index (GAPI) and the most recent Analytical GREEness metric (AGREE) were tested to evaluate two proposed MEKC and HPTLC methods for the simultaneous determination of the antifungal drug sertaconazole (SER) and two co-formulated preservatives methyl paraben (MEP) and sorbic acid (SOR). Method I was micellar electrokinetic capillary chromatography (MEKC). Electrophoretic conditions were optimized to improve separation, sensitivity, and rapidity. The proposed method used a fused silica capillary (50 cm × 50 μm id), and the background electrolyte was 50 mM acetate buffer pH 4.6 containing 15 mM SDS with 17 s injection time. The applied voltage was 30 kV. The diode array detector (DAD) was set at 210 nm for measurement of SER and 254 nm for both MEP and SOR. The Three compounds were resolved in less than 6 min with migration times 3.07, 4.29, and 5.97 min for SER, MEP, and SOR respectively. The described method was linear over the range of 5–100 μg/mL for SER, MEP and SOR with correlation coefficients >0.9995. For method II: high-performance thin-layer chromatography (HPTLC) analysis was carried out on aluminum-backed sheet of silica gel using chloroform-ethyl acetate (3:7) as mobile phase. Retardation factors were 0.20, 0.71, and 0.88 for SER, MEP, and SOR respectively. Quantification was achieved with UV densitometry at 210 nm for SER and 254 nm for MEP and SOR. The linearity ranges were 0.1–1 μg/spot for the three drugs with correlation coefficients >0.9998. The analytical performance of both methods was thoroughly validated according to International Conference on Harmonization (ICH) guidelines with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The proposed MEKC and HPTLC methods were successfully applied for estimation of the studied drugs in laboratory prepared mixtures and in the cream and spray dosage forms.

Formulation and evaluation of proniosome loaded sertaconazole nitrate for topical application

Proniosomal technology is a novel solution for poorly soluble drugs. Proniosomes are water-soluble carrier particles which are coated with non-ionic surfactants. Proniosomal gels were prepared by coacervation phase separation method using non-ionic surfactants, lipid carriers and cholesterol as a membrane stabilizer. FTIR compatibility studies revealed that the drug and excipients were compatible. All formulations were evaluated for pH, drug content, extrudability, spreadability, viscosity, in-vitro, ex-vivo, skin irritation and stability studies. Among formulations prepared, F80H1 has shown higher % EE (83.02) and least diffusion through dialysis membrane i.e., 17.68%. With ex-vivo studies, F80H1 formulation has shown highest skin deposition and lower flux of sertaconazole nitrate through the rat skin. F80H1 was selected as final optimized formulation. F80H1 exhibited good stability and SEM studies revealed that the vesicles were spherical in shape. The optimized formulation was found to follow zero order release kinetics and korsmeyer-peppas release mechanism. F80H1 found to be non-irritant and stable from skin irritation and stability studies.

MODERN DIAGNOSIS AND COMPLEX TREATMENT OF MICROSPORIA IN ATHLETES

This study reflects the features of the clinical course of microsporia in children and adults who attended sports sections. Athletes who attended freestyle and Greco-Roman wrestling sections a typical clinical picture in the form of “athlete-wrestler's symptom” is observed: the rash was localized mainly in the right half of the head (on the right temporal, right postaural, right parietal and occipital areas), often with a migration to smooth skin on the face and neck, from 1 to 5, rounded form, with slight peeling on the surface, in the form of prints fingers. Hair in the lesion areas is broken at the level of 3-6 mm. Features of the clinical course are caused by basic techniques and holds of hands with fingers applied in these sports. 
 In order to improve the exact specific diagnosis of microsporia in athletes, a method of modern molecular genetic diagnostics based on polymerase chain reaction (PCR) has been developed, which allows identifying the Microsporum canis pathogen at the DNA level. 
 A complex method of therapy, which includes the use of probiotic-vitamin-mineral complexes “Bion 3 Kid”, “Bion 3” or probiotic-vitamin preparation “Breveluck” in combination with systemic antimycotics Griseofulvin, Terbinafine and 2% cream Sertaconazole nitrate is effective and safe in microsporia treatment in athletes. All 40 patients with microsporia have clinically and etiologically recovered as a result of treatment. Developed modern complex treatment of patients with microsporia contributed to increase in the effectiveness of treatment, prevention of microsporia recurrence, acceleration of clinical and mycological recovery, prevention of the disease of athletes with acute respiratory viral infections during their stay in sports and children's groups, even in the cold periods of year.

Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate

The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug – sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer – dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics. A penetration enhancement efficacy of MNs was evaluated in vitro using porcine ear skin in parallel with the efficacy of formerly developed chemical penetration enhancer – biocompatible microemulsion (ME) formulation. Moreover, an ability of solid silicon MNs to significantly improve delivery of SN from ME into the skin has also been investigated. The obtained results showed that dissolving MNs had satisfying morphological properties and mechanical strength. This type of MNs provided comparable drug deposition in the skin as ME formulation, but also revealed an indication of percutaneous absorption of a portion of the administered drug dose. However, the penetration/permeation study results were largely influenced by experimental setup and dosing regimen. Although solid silicon MNs assisted SN dermal delivery led to increase of drug cutaneous retention (1.9-fold) under infinite dosing regimen, the synergistic action of solid MNs and ME applied under finite dosing was more pronounced in comparison with the application either of physical (dissolving MNs) or chemical enhancer (ME) alone. Namely, SN amount accumulated into the skin increased up to 4.67 and 4.37 folds in comparison with ME and dissolving MNs alone, respectively, while reaching a significant decrease in drug permeation through the skin compared to the use of dissolving MNs. Application of ME per se was the only approach that provided selective in vitro dermal drug delivery without SN permeation across the skin. However, despite both types of the used MNs lead to SN permeation in vitro, the ratio between the drug amount deposited in the skin and SN content permeated was significantly higher for the combined approach (12.05) than for dissolving MNs (2.10). Therefore, a combination of solid silicon MNs and biocompatible ME favoured more pronouncedly SN skin accumulation, which is preferable in the treatment of skin fungal infections.