Fungi are the common pathogens found in critically ill patients in hospitals. In the clinical practice, Cryptococcus spp. and Candida spp. are the most frequently isolated yeasts.

The invasive fungal infections occur in patients on the therapy of immunosuppressive and antineoplastic agents, prosthetic devices and grafts and more aggressive surgery and broad-spectrum antibiotics. Patients suffering from pancreatitis, burns, HIV infection and neutropenia are also pre-disposed to fungal infection.¹

Agents that shows therapeutic effects in fungal infections are known as antifungal agents. Antifungal agents are classified in table 1.

Table 1. Classification of antifungal agents

Category	Examples of drugs
Polyene antibiotics	Amphotericin B
Azole derivatives: Imidazole	Ketoconazole, Miconazole
Triazole	Fluconazole, Itraconazole, Voriconazole,
	Posaconazole, Ravuconazole
Echinocandin	Capsofungin, Anidulafungin, Micafungin
Antimetabolite	Flucytosine (5-FC)
----	Nikkomycin
Topical Antifungal Drugs
Polyene antibiotics	Amphotericin B, Nystatin, Hamycin, Natamycin (Pimaricin), Rimocidin, Hitachimycin, Filipin
Others	Tolnaftate, Undecyclinic acid, Povidone iodine, Triacetin, Gentian violet, Sodium thiosulphate, Cicloporox olamine, Benzoic acid, Quinidochlor
Systemic Antifungal Drugs for Superficial Infections
Heterocyclic benzofurans	Corticofunvin, Griseofulvin
Allylamine	Terbinafine, Butenafine, Naftifine

Sertaconazole is a new antifungal agent with benzothiopene imidazole moiety with chemical name. Its nitrate salt is available for which IUPAC name is nitrate salt of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene). Its molecular formula is C₂₀H₁₆O₄N₃Cl₃S and molecular weight is 500.8 Da, CAS: 99592–32–2.

Fig. 1. Chemical structure of sertaconazole

Sertaconazole is a topical azole derivative with a basic benzothiophene moiety differentiating this drug from other azoles used in the treatment of fungal infections.² It is practically insoluble in water and the lipophilic portion is soluble in organic solvents (slightly soluble in N-octanol (0.069%), acetone (0.95%), chloroform (1.5%), ethanol (1.7%).³

A summary of physicochemical properties of sertaconazole are tabulated below (table 2).⁴

Table 2. Physicochemical characteristics of Sertaconazole

Sr. No.	Parameters	Characteristics
1	Physical description	Solid
2	Molecular Weight	437.763 g/mol
3	XLogP3	6.3
4	Hydrogen Bond Donor Count	0
5	Hydrogen Bond Acceptor Count	3
6	Rotatable Bond Count	6
7	Topological Polar Surface Area	55.3 A^2
8	Heavy Atom Count	27
9	Formal Charge	0
10	Complexity	488
11	Isotope Atom Count	0
12	Defined Atom Stereocenter Count	0
13	Undefined Atom Stereocenter Count	1
14	Defined Bond Stereocenter Count	0
15	Undefined Bond Stereocenter Count	0
16	Covalently-Bonded Unit Count	1
17	Compound is Canonicalized	Yes
18	Solubility	Practically insoluble (6.37´10^-03 g/L)
19	Octanol/Water Partition Coefficient (LogP)	6.2
20	Log S	-4.8
21	pKa	6.77
22	Polarizability	42.93 Å³

Pharmacological actions:

Indications: It is prescribed for the treatment of interdigital tinea pedis (topical) caused by Epidermophyton floccosum, Trichophyton mentagrophytes and Trichophyton rubrum in immunocompetent patients 12 years of age and older.

Pharmacodynamics:

Sertaconazole is an imidazole/triazole type antifungal agent which selectively inhibit fungal cytochrome P450 sterol C-14 α-demethylase. This enzyme is essential for fungal cell wall synthesis as it converts lanosterol to ergosterol. It inhibits ergosterol synthesis in proportion to the concentration of the drug causing direct damage to cell membrane of C. albicans due to its mixed structure.^5,6 The properties of ergosterol maintain internal fluidity of the membrane. An interaction of this drug with cytochrome P450 (in mono-oxygenase or hydroxylase; 14-α-demethylase enzymes) inactivate the enzyme through bond formation between the drug and the iron atom of the haem which causes reduction in the ergosterol biosynthesis through the production of an intermediate lanosterol, as a result of which the cell integrity (cellular architecture, membrane permeability and fluidity) is affected. In general, azole derivatives inhibit the biosynthesis of ergosterol and filamentation in C. albicans, but in case of sertaconazole, it causes direct damage to the cell membrane.⁶ Due to an increase in cellular permeability there is a loss of intracellular ATP, lysis of cell organelles, destruction of cytoskeleton and reduction in the number of viable cells up to 90%. Thus, the fungicidal effect of the drug came into effect at high concentrations.^5,6

It exhibits in vitro fungistatic activity against Candida species and Cryptococcus neoformans. for intracranial and systemic fungal infections in normal and immunocompromised animal models⁴

Fig. 2. Site of action of antifungal drugs in yeast like cell

This drug also exhibits anti-inflammatory action; however, the mechanism for this action has not been known yet. The cellular mechanisms were investigated for its anti-inflammatory potential in human peripheral blood mononuclear cells and keratinocytes; and it was found to activate the proinflammatory p38 mitogen-activated protein kinase resulting in the induction of cyclooxygenase-2 (COX2) which results in the release of prostaglandin E2. This drug also suppressed the release of cytokines. COX-2 inhibitor NS398 reversed the sertaconazole-mediated inhibition of TPA-induced ear oedema in an in vivo mouse model of tetradecanoyl phorbol acetate (TPA)-induced dermatitis. Biochemical analysis of tissue biopsies in sertaconazole-treated mice, revealed an increase in PGE2 levels. Thus, sertaconazole provides anti-inflammatory therapeutic benefits via activation of the p38-COX-2-PGE2 pathway.⁷

Pharmacokinetics:

Sertaconazole penetrates the horny layer of skin and the therapeutic concentrations may be found after a long period of time, avoiding the potential risk of systemic absorption. The water solubility is of 0.0064g/L and log P is 6.2. In a preclinical study, after application of 2% cream of radioactively marked sertaconazole to the skin, the plasma concentrations were found below 0.011% after 5 hr.⁸ After topical application at increasing doses, the cutaneous absorption in humans has also been described to be 72% of the dose applied 24 hr after the application. There were no cardiac, hematologic or body temperature changes observed at 13^th day, also there was not any alteration in blood testosterone level, thus provide the good safety profile of the drug.⁹ It has been reported to retained in the skin for long periods of time after topical applications once or twice a day, reaching antifungal concentrations at 72 hr.¹⁰ The main routes of elimination of drug are faecal and renal route 61 and 4%, respectively, for endovenous administration; 30 and 0.4% for administration and 17 and 0.6% for the skin.⁸

Table. 3. Pharmacokinetic and pharmacodynamic profile of sertaconazole

Sr. No.	Property name	Description
1.	Absorption	Bioavailability is negligible
2.	Protein binding	>99% to plasma
3.	Affected organisms	Yeast and other fungi
4.	Contraindications	in hypertensive patients
5.	Warnings and Precautions	in allergic patients, during pregnancy and breastfeeding. Its use is prohibited for children younger than 12 years of age Excess dosage should be avoided, otherwise it may worsen the condition
6.	Side Effects	Local: Skin tenderness and dry skin. Allergic reactions: Rash, itching Rash, swelling of mouth, lips, face, difficulty in breathing, tightness in chest^[11]
7.	Drug Interactions	No interactions
8.	P-glycoprotein inhibitor I	Non-inhibitor
9.	P-glycoprotein inhibitor II and renal organic cation transporter	Inhibitor
10.	CYP450 2C9 substrate, CYP450 2D6 substrate, CYP450 3A4 substrate	Non-substrate
11.	CYP450 1A2 substrate, CYP450 2C9 inhibitor, CYP450 2D6 inhibitor, CYP450 2C19 inhibitor, CYP450 3A4 inhibitor	Inhibitor
12.	Carcinogenicity	Non-carcinogenic
13.	Biodegradation	Not readily biodegradable
14.	Rat acute toxicity	2.4642 LD50, mol/kg
15.	hERG inhibition (predictor I) and (predictor II)	Weak inhibitor and inhibitor
16.	Human Intestinal Absorption, Blood Brain Barrier, Caco-2 permeable	Positive

Safety profile of sertaconazole:

Preclinical studies:

With the use of animal models, the tolerability profile of sertaconazole has been determined in which absence of associated adverse effects was demonstrated.^9,11,12 LD₅₀i.e. the median lethal dose of sertaconazole was found to be indeterminable because at maximum administered dose of 8000mg/kg mortality (in rat and mice, single doses of sertaconazole were given by subcutaneous, oral and intraperitoneal routes), the median did not allow LD50 calculation.¹³ After single administration of the drug, toxic effects were not detected. These were determined by subacute toxicity and maximum tolerated dose studies over a period of 28 days. It has been found that sertaconazole did not induce hepatomegaly in dermal administered rabbits.^8,14 Even in case of accidental ingestion or overdose of sertaconazole, it was safe because of its reduced absorption.¹³ There were no differences found between the effects produced by sertaconazole administration and other azoles for the topical treatment. A lesser rise in body weight had been reported in case of sertaconazole in the animals treated over 5 weeks with 300mg/kg of drug (in case of rats) and over 11 weeks with 150mg/kg (in case of ferrets).¹⁵ Additionally, inhibition of the synthesis of adrenal steroidal hormone were detected only after high dose drug administration. As a result, changes in ovaries and ductal hyperplasia of the mammary gland and endometrium of treated female ferrets occur.¹⁵ The drug administration was not associated with inflammatory, necrogenic and degenerative changes, in comparison to miconazole and clotrimazole.^15,16 In comparison with ketoconazole, miconazole or bifonazole, it demonstrates a low toxicological risk without any signs of pro-mutagenicity mutagenicity and clastogenicity. No interference with the process of chromosomal segregation was found in studies performed with prokaryotic and eukaryotic cells.^14,17

Clinical Studies data:

Sertaconazole is well tolerated in patients who have gynaecological and dermatological candidiasis. Frequency of adverse events is similar to the placebo vehicle treated patients and its safety has been demonstrated in children.¹⁸ Side effects which have been demonstrated with topical application of sertaconazole were contact dermatitis, eczema, itching and skin tenderness. There was no evidence of sensitizing action noticed in healthy volunteers after topical application of sertaconazole or vaginal suppository.¹² Only local irritation after insertion of vaginal tablet was reported in case of vaginal tablet administration, severe adverse effects were absent. Minor side effects like formation of vesicles after application of their topical application of econazole, ketoconazole, bifonazole, clotrimazole, miconazole was observed.⁹

With 2% cream formulation or solution, sertaconazole does not induce contact dermatitis and only 1.1% of patients involved in comparative study of sertaconazole cream and solution revealed adverse events.^9,19-21 Patients who had previous sensitivity to some azole derivatives are prone to contact dermatitis. Sertaconazole may be administered without photosensitivity and by products produced by direct sunlight associated degradation.^9,13,17

Clinical trials under investigation (Phase II completed):

A prospective, double-blind, randomized, vehicle-controlled, parallel-group, multi-centre clinical trial was conducted Stander et al in the subjects with atopic dermatitis to compare the efficacy of topical sertaconazole 2% cream with vehicle to assess its safety and local tolerability and in reducing chronic pruritus. 70 subjects applied either of the 2 treatments for a period of 4 weeks twice daily on affected, itchy skin areas. The efficacy of treatment was checked on the basis of the item itch intensity on a 5-point verbal rating scale, quality of life, state of atopic dermatitis (Scoring Atopic Dermatitis; SCORAD), therapy benefit and insomnia. There was no significant difference observed between active treatment and vehicle for any of the investigated parameters, at any of the time-points. Thus, it was concluded that sertaconazole 2% cream did not exert anti-pruritic effects that were better than vehicle in subjects with atopic dermatitis under the experimental conditions of the study.³²

Stability:

Sertaconazole nitrate in solid form as well as suspension form is highly stable under real time and accelerated time studies. Solid sertaconazole nitrate were studied against varying light, humidity and temperature whereas suspension form was studied against different pH conditions (acidic/basic). Sertaconazole nitrate in solid form can be stored for five years under normal environment conditions in amber glass bottles tightly sealed.³

Formulations:

Cubosomes:

STZ is a poorly soluble antifungal agent and 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, the drug loaded cubosomes (STZ-CUBs) were prepared, characterized and optimized based on a 33 central composite face-centered design. Optimized formulation (CUB-opt) showed maximum desirability (0.905), particle size (PS) of 216.55±2.33nm, with solubilization efficiency (SE%) of 94.50±0.51%, zeta potential (ZP) of 34.00±6.93mV and polydispersity index (PDI) of 0.229±0.11. It showed discrete cubic shaped structures under the transmission electron microscope, Moreover, it exhibited a promising storage stability, terminal sterilization stability and mucoadhesive behaviour. The corneal permeation study (ex vivo) revealed its ability to enhance the permeability coefficient (KP) and the steady state flux of STZ, in comparison to STZ-suspension. Thus, in the in vivo corneal tolerance study, CUB-opt formulation was found to be safe on the corneal tissues and in the in vivo corneal uptake study, demonstrated a superior corneal penetration power.³³

Topical hydrogel:

A microemulsion (ME) based hydrogel of sertaconazole had studied for the treatment of cutaneous fungal infection as a topical delivery. It was investigated in pseudo-ternary phase diagrams using different ME formulations using Tween 80, oleic acid, water and propylene glycol. Carbopol 940 (0.75%, w/w) was used to formulate hydrogel of STZ microemulsions (HSM) and evaluated was done in comparison to commercial cream of STZ ex vivo and in vitro. The optimized formulation (HSM-4), comprising water (24.55%, w/w), tween 80 (33.35%, w/w), propylene glycol (33.35%, w/w) and oleic acid (8.75%, w/w), the permeation rate of the drug was observed higher as compared to other HSMs and commercial cream. HSM-4 was stable and had 3 times higher drug retention capacity in skin and did not caused any erythema or edema than commercial cream based on skin sensitivity study on rabbit. The average zone of inhibition of HSM-4 (23.54±0.72mm) was higher than commercial cream (16.53±0.63mm) against Candida albicans due to permeation enhancing effect of ME and skin retention effect of HSM. Thus, it was concluded the concentration of STZ could be decreased due to the high permeation and anti-fungal effect of STZ in HSM-4 in case of cutaneous fungal infections.³⁴

Nano-sized colloidal carriers:

This study was carried out to explore the feasibility of microemulsion formulation as a nano-sized colloidal carrier for dermal delivery of voriconazole and sertaconazole. The pseudo-ternary phase diagrams were prepared to identify the area of microemulsion existence and the optimum compositions were determined based on water, ethanol, Tween 80 and oleic acid. The microemulsions were characterized in terms of conductivity, optical isotropy, refractive index and pH, thermo- dynamic stability, globule size and its distribution. In comparison to the conventional topical formulations, the localization and in vitro penetration of voriconazole and sertaconazole into deeper skin layers from the developed microemulsions were investigated. The results revealed the enhanced drug retention and interaction between the microemulsion components and skin through confocal laser scanning microscope and ATR-FTIR spectroscopy respectively. The in vitro antifungal activity was checked using four Candida species and it was observed that by the topical application of the formulated microemulsions of both the drugs, minimum inhibitory concentration (MIC) could be reached. Thus, microemulsions could be a potential colloidal carrier for improving topical delivery of sertaconazole and voriconazole.³⁵

Nano-vesicular systems:

Different phospholipid based nanovesicles, namely ethosomes liposomes, transferosmes, glycerosomes, were prepared and evaluated in-vitro for zeta potential value, entrapment efficiency, vesicle size and morphology followed by ex-vivo evaluation through skin permeation and penetration. 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 STZ loaded vesicular gel with commercial cream (Dermofix1). zeta potential vesicle size and entrapment efficiency were dependent upon vesicle composition. Vesicular formulae enhanced drug permeation in comparison to commercial cream where tansferosomal system containing 0.15% sodium deoxy-chloate (SDC) and3% soy phospholipid (SPC) showed highest flux (645mg/cm²/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. A significant preventive effect was observed (in-vivo) in immune compromised rat model. Furthermore, in immunocompromised rat model with fungal skin infection, the developed STZ-loaded tansferosomal gel revealed lowest histopathological changes in comparison to commercial cream.^[36]

Table 4. Summary of clinical studies data

Sr. No.	Type of study	Dosage form	Drugs used	Disease/ condition	Conclusion
1.	Open, randomized, and comparative study²²	Vaginal tablets	sertaconazole (single-dose) vaginal tablet (500 mg) and econazole (3-dose) vaginal tablet (150mg)	Vulvovaginal candidiasis	Sertaconazole treated group showed a significantly better clearance rate, a more rapid response for symptom relief for candidiasis than econazole treated group (100% vs. 72.2% on day 7, p = 0.013; 100% vs. 77.8% on day 14, p = 0.030), based on smear method results but there was no difference in overall symptom relief between both groups on day 14. Single-dose sertaconazole proved to be a more convenient and symptom-relieving treatment for VVC especially in women with relapse VVC
2.	Double-blind, randomized controlled trial²³	Cream	sertaconazole 2% cream and hydrocortisone 1% cream	Seborrheic dermatitis	SD lesions cleared significantly (p b .05) in both treatment groups (p N .05) and the rate of adverse events was similar in both groups. The IP was found to be better in case of hydrocortisone treated group in Week 2 but similar in two groups towards the end of study. Treatment with topical sertaconazole may be regarded as a substitute for topical corticosteroid medications due to the fewer adverse events and similar efficacy
3.	A single blind, randomized control trial²⁴	Cream	Terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream twice daily for 3 weeks	localized tinea corporis and tinea cruris	When the two groups were compared for complete cure, at the end of 1(st) and 2(nd) week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2(nd) week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance.
4.	Tolerability studies^{25, 26}	Cream	8.7% sertaconazole and 13.4% econazole	Candida vulvovaginitis,	local tolerability was reported as excellent in 95% without causing any local adverse effect. Only five patients had local burning sensation while the general clinical tolerability was found to be excellent in 100% of patients
5.	A multicentred, randomized, double-blind study²⁷	Sustained release suppositories	300mg sertaconazole and 150mg econazole	vulvovaginal candidiasis	There were no differences between the two groups for the rates of clinical recovery (disappearance of signs and symptoms) and mycological recovery (negative culture), 1 week after the first application (62.1 and 67.7%, respectively), 1 week after the second application for women treated twice (72.3 and 80.6%, respectively) and for all patients 1 month after the last application (65.3 and 62.0%, respectively). Among the patients cured 1 week after the last application, the mycological recurrence rate after 1 month was significantly higher in the econazole group (32.7 vs. 19.8%, P=0.035). There was a trend towards better efficacy of sertaconazole after the first application, whereas the two treatments had similar efficacy in women treated twice. There were no serious adverse events and only local irritation was reported, without any statistically significant difference between the two groups. Single topical administration of sertaconazole and econazole had similar efficacy and safety but the former is associated with a lower rate of mycological recurrence one month after achieving a negative culture.
6.	Randomized double-blind²⁸	Nail patches	2.2 cm² nail patch containing sertaconazole 3.63mg and another patch containing no antifungal agent	onychodystrophy and onychomycosis	Sertaconazole was detected in all sertaconazole-treated nail samples with mean concentrations of >100 microg/g, which exceeds the minimum inhibitory concentrations (MICs) for all relevant fungi in this context. Measurements of the residual dose in the patches suggested that 16-71% of the active ingredient had penetrated into the nail. No plasma sertaconazole concentrations could be detected. By virtue of their positive influence (occlusion) on water and lipid metabolism in dystrophic nails, nail patches should have beneficial therapeutic effects in onychodystrophic conditions. No systemic absorption of the active ingredient was detectable, which should exclude unwanted systemic effects of the drug.
6.	An open-label, multicentred study¹⁸	Cream	2% sertaconazole cream during a 2-week period	14 children had tinea corporis, 1 had tinea cruris, and 1 had tinea pedis. Microsporum canis was identified in 50% of cultures and Trichophyton rubrum in 42%.	Clinical cure was achieved in 31% of patients after 1 week, 75% after 2 weeks, and 100% after 4 weeks. once-daily topical sertaconazole is an effective and well-tolerated treatment for pediatric patients with dermatophytosis
7.	A double-blind randomized clinical trial²⁹	Cream	sertaconazole 2% cream; pimecrolimus 1 % cream	seborrheic dermatitis	Sertaconazole 2% cream was more effective (satisfaction level 90%) than pimecrolimus 1 % cream (satisfaction level 80%) after 28 days
8.	A double-blind randomized clinical trial³⁰	Cream	ertaconazole 2% cream and tacrolimus 0.03% cream	seborrheic dermatitis	observed after 28 days that sertaconazole 2% cream was more effective (90% satisfactory result) than tacrolimus 0.03% cream (83.3% satisfactory results)
9.	Prospective, randomized, multicentric study³¹	Cream	sertaconazole nitrate 2% cream vs. miconazole	cutaneous dermatophytosis	Moreover, 62.3% patients had complete clinical cure in the sertaconazole group (P < 0.05) compared with 44.6% in miconazole users. therapy with sertaconazole cream (2%) provided a better efficacy and tolerability compared with the miconazole cream (2%) and could thus be a therapeutic option in cutaneous dermatophytosis.

Microsponge:

Microsponges loaded with sertaconazole nitrate were prepared with five different proportions of the polymer by using quasi emulsion solvent diffusion (Eudragit RS 100). The developed microsponges were checked for production yield, drug content, particle size and entrapment efficiency. Sherical shape and pores were checked by scanning electron microscopic images of microsponges. Mercury intrusion porosimetry technique confirmed the porous nature of microsponges. Microsponges were evaluated for drug content, in vitro drug release, pH, texture profile analysis after incorporation into a 1% corbopol gel. The batch F IV was found to be optimal as it showed 69.38% controlled drug release in 8 h (Higuchi model).³⁷

Flexisomes:

Flexisomes are self-aggregating, flexible, deformable lipidic vesicles possessing an aqueous core. A 3² factorial design was used to optimize the effects of the critical material attributes of concentration of phospholipid (X1) and edge activator (X2) on the critical quality attributes of particle size (Y1), entrapment efficiency (Y2), and deformability index (Y3). Statistical analysis was performed to be identify the best fit model and determine its significance. The sizes of the optimized STZ-FS were found to be 246.2 ± 2.49nm with entrapment efficiencies of 86.16 ± 0.56% and deformability indices of 30.46 ± 0.41. Zeta potential analysis showed negatively charged surface with a zeta potential value of -30.9 mV. TEM analysis showed spherical shapes, confirming the vesicular characteristics. The optimized STZ-FS were further formulated into hydrogels. The % drug diffusion of STZ-FS hydrogels was found to be 13.24% and drug deposition in the skin layers was found to be 83.54%, showing that a high concentration of the drug was available at the site of action. The zone of inhibition STZ-FS hydrogel (30 mm) was higher than the marketed formulation (22 mm) and the plain STZ hydrogel (14 mm) against Candida albicans. Hence, it was concluded that STZ loaded STZ-FS shows high flexibility and enhanced antifungal activity. STZ-FS are thus found to be potential carriers for drug deposition in skin layers without disturbing their integrity.³⁸

Pharmacoeconomics/Marketed formulation:^[4]

Ertaczo 2% Cream 30 gm Tube with cost= 89.28USD

Ertaczo 2% cream with cost= 2.6USD

Patents: 1H-imidazole derivative compounds and pharmaceutical compositions containing the same.

The 1H-imidazole derivative compound and its nontoxic addition salts, particularly the nitrate addition salt, are more effective as antimycotic agents and are unexpectedly safer than the corresponding prior art compounds, especially the compound in which the sulphur atom of the benzothiophene ring of the above compound is replaced by an oxygen atom. Pharmaceutical compositions containing an effective amount of the compound of formula I, e.g. 1 to 5% by weight, in a pharmaceutical carrier are safer, more effective, and, in some cases, more reliable with fewer side effects than currently used antimycotic preparations.^[39]

CONCLUSION:

Pharmaceutical R&Ds are currently facing a huge technical challenge in the discovery of new antifungal targets and therefore, development of effective antifungal agents since a very limited number of antifungal agents are available for the management of fungal infections. Many probable antifungal agents are existing at different stages of their development pipeline, however, during more than last many years, amphotericin B has been almost the only option available for invasive mycoses. Nevertheless, great efforts are being made in this direction. Pharmaceutical scientists are focusing on the development of new azole or polyene derivatives, development of novel formulations of existing antifungal drugs and antifungal combination therapy. Sertaconazole is one of the latest imidazole derivatives that has broad-spectrum of activities (antifungal, antibacterial and antiprotozoal activities), good pharmacokinetics and excellent safety and toxicological profile. It enables the use of sertaconazole in clinical practice for a variety of disorders and proves it an excellent drug.

ACKNOWLEDGEMENT:

Authors are thankful to second International Conference of Pharmacy, held at School of Pharmaceutical Sciences, Lovely Professional University on September 13-14, 2019 to fund the publication of this manuscript.

CONFLICTS OF INTEREST:

Authors declare none.

REFERENCES:

1. Eggimann PGJ, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 3(11): 2003: 685-702.

2. Raga MM, Moreno-Manas M, Cuberes MR, Palacin C, Castello JM, Ortiz JA. Synthesis and antimycotic activity of (benzo[b]thienyl)methyl ethers of 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-ethanol and of (Z)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone oxime. Arzneimittelforschung. 42(5A): 1992: 691-694.

3. Albet C, Fernández JM, Sacristán A, Ortiz JA. Physico-chemical properties, analytical determinations and stability of sertaconazole nitrate. Arzneimittelforschung. 42(5A): 1992: 695-698.

4. https://www.drugbank.ca/drugs/DB01153#taxonomy

5. Agut J, Palacín C, Sacristán A, Ortiz JA. Inhibition of ergosterol synthesis by sertaconazole in Candida albicans. Arzneimittelforschung. 42(5A): 1992: 718-720.

6. Agut J, Palacín C, Salgado J, Casas E, Sacristán A, Ortiz JA. Direct membrane- damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity. Arzneimittelforschung. 42(5A): 1992: 721-724.

7. Sur R, Babad JM, Garay M, Liebel FT, Southall MD. Anti-Inflammatory Activity of Sertaconazole Nitrate Is Mediated via Activation of a p38-COX-2-PGE2 Pathway. Journal of Investigative Dermatology. 128(2): 2008: 336-344.

8. Agut J, Moren M, Rego M, Sacristán A, Ortiz JA. Pharmacokinetic evaluation of labelled sertaconazole after dermal application. Arzneimittelforschung. 42(5A): 1992: 748-751.

9. Farré M, Ugena B, Badenas JM, Márquez M, Roset P, Ortiz JA. Pharmacokinetics and tolerance of sertaconazole in man after repeated percutaneous administration. Arzneimittelforschung. 42(5A): 1992: 752-754.

10. Palacin C, Tarrago C, Sacristan A, Ortiz J. A Antifungal activity of sertaconazole in the cutaneous retention time test. Journal of medical mycology. 5(1): 1995: 35-39.

11. Croxtall JD, Plosker GL. Sertaconazole- A Review of Its Use in the Management of Superficial Mycoses in Dermatology and Gynaecology. Drugs. 69(3): 2009: 339-359.

12. Umbert P, Nasarre J, Bello A, Herrero E, Roset P, Márquez M, Torres J, Ortiz JA. Phase II study of the therapeutic efficacy and safety of the new antimycotic sertaconazole in the treatment of superficial mycoses caused by Candida albicans. Arzneimittelforschung. 42(5A): 1992: 757-760.

13. Grau MT, Romero A, Sacristán A, Ortiz JA. Acute toxicity studies of sertaconazole. Arzneimittelforschung. 42(5A): 1992: 725-726.

14. Romero A, Grau MT, Villamayor F, Sacristán A, Ortiz JA. Reproduction toxicity of sertaconazole. Segment II (teratology) and segment III (peri-postnatal toxicity). Arzneimittelforschung. 42(5A): 1992: 739-742.

15. Romero A, Villamayor F, Grau MT, Sacristán A, Ortiz JA. Chronic toxicity studies of sertaconazole after oral administration to rats and ferrets. Arzneimittelforschung. 42(5A): 1992: 732-738.

16. Romero A, Villamayor F, Grau MT, Sacristán A, Ortíz JA. Subacute toxicity and maximum tolerable dose of sertaconazole in repeated administration studies. Arzneimittelforschung. 42(5A): 1992: 727-732.

17. Grau MT, Romero A, Sacristán A, Ortiz JA. Dermal tolerance and phototoxicity studies of sertaconazole. Arzneimittelforschung. 42(5A): 1992: 746-747.

18. Van Esso D, Fajo G, Losada I, Vilallonga M, Casanovas JM, Clanxet J, Aliaga A. Sertaconazole in the treatment of pediatric patients with cutaneous dermatophyte infections. Clinical Therapeutics. 17(2): 1995: 264-269.

19. Borelli C, Klövekorn G, Ernst TM, Bödeker RH, Korting HC, Neumeister C. Comparative study of 2% sertaconazole solution and cream formulations in patients with tinea corporis, tinea pedis interdigi- talis, or a corresponding candidosis. Am J Clin Dermatol. 8(6): 2007: 371-378.

20. Drouhet E, Dupont B. In vitro antifungal activity of sertaconazole. Arzneimittelforschung. 42(5A): 1992: 705-710.

21. Romaguera C, Herrero E, Márquez M, Torres J, Ortiz JA. Study on the sensitizing capacity of the new antimycotic sertacona- zole in the treatment of cutaneous mycoses. Arzneimittelforschung. 42(5A): 1992: 754-756.

22. Wang PH, Chao HT, Chen CL, Yuan CC. Single-dose Sertaconazole Vaginal Tablet Treatment of Vulvovaginal Candidiasis. J Chin Med Assoc. 69(6): 2006: 259-263.

23. Balighi K, Ghodsi SZ, Daneshpazhooh M, Ghale-Baghi S, Nasimi M, Azizpoura A. Hydrocortisone 1% cream and sertaconazole 2% cream to treat facial seborrheic dermatitis: A double-blind, randomized clinical trial. Int J Women's Dermatol. 3(2): 2017: 107-110.

24. Choudhary S, Bisati S, Singh A, Koley S. Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial. Ind J Dermatol. Indian J Dermatol. 58(6): 2013: 457-460.

25. Susilo R, Korting HC, Strauss UP, Menke G, Schuster O, Menke A. Rate and extent of percutaneous absorption of sertaconazole nitrate after topical administration. Arzneimittelforschung. 55(6): 2005: 338-342.

26. Quereux C1, Gelas B, Chevallier T, Petit F, Micheletti MC. Evaluation of the efficacity and speed of action of sertaconazole nitrate suppository and cream combined treatment for vulvovaginal candidiasis. Gynecol Obstet Fertil. 28(3): 2000: 238-244.

27. Dellenbach P, Thomas JL, Guerin V, Ochsenbein E, Contet-Audonneau N. Topical treatment of vaginal candidosis with sertaconazole and econazole sustained-release suppositories. Int J Gynaecol Obstet. 71: 2000: S47-S52.

28. Susilo R, Korting HC, Greb W, Strauss UP. Nail penetration of sertaconazole with a sertaconazole-containing nail patch formulation. Am J Clin Dermatol. 7(4): 2006: 259-262.

29. Goldust M, Rezaee E, Raghifar R. Treatment of seborrheic dermatitis: comparison of sertaconazole 2% cream versus pimecrolimus 1% cream. Irish J Med Sci. 182(4): 2013: 703-706.

30. Goldust M, Rezaee E, Raghifar R, Hemayat S. Treatment of seborrheic dermatitis: the efficiency of sertaconazole 2% cream vs. tacrolimus 0.03% cream. Ann Parasitol. 59(2): 2013: 73-77.

31. Sharma A, Saple DG, Surjushe A, Rao GR, Kura M, Ghosh S, Bolmall C, Baliga V. Efficacy and tolerability of sertaconazole nitrate 2% cream vs. miconazole in patients with cutaneous dermatophytosis. Mycoses. 54(3): 2011: 217-222.

32. Ständer S, Metz M, Ramos F MH, Maurer M, Schoepke N, Tsianakas A, Zeidler C, Luger TA. Anti-pruritic Effect of Sertaconazole 2% Cream in Atopic Dermatitis Subjects: A Prospective, Randomized, Double-blind, Vehicle-controlled, Multi-centre Clinical Trial of Efficacy, Safety and Local Tolerability. Acta Derm Venereol. 96(6): 2016: 792-796.

33. Younes NF, Abdel-Halim SA, Elassasy AI. Corneal targeted Sertaconazole nitrate loaded cubosomes: Preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies. International Journal of Pharmaceutics. 553(1-2): 2018: 386-397.

34. Sahoo S, Pani NR, Sahoo SK. Microemulsion based topical hydrogel of sertaconazole: Formulation, characterization and evaluation. Colloids and Surfaces B: Biointerfaces. 120: 2014: 193-199.

35. Moammal S. Qurt İE, Seher Birteksöz Tan, Meryem Sedef Erdal, Ahmet Araman, Sevgi Güngör. Voriconazole and sertaconazole loaded colloidal nano-carriers for enhanced skin deposition and improved topical fungal treatment. J Drug Del Sci Technol. 48: 2018: 215-222.

36. Abdellatif MM, Khalil IA, Khalil MAF. Sertaconazole nitrate loaded nanovesicular systems for targeting skin fungal infection: In-vitro, ex-vivo and in-vivo evaluation. Int J Pharmaceutics. 527(1-2): 2017: 1-11.

37. Pande VV, Kadnor NA, Kadam RN, Upadhye SA. Fabrication and Characterization of Sertaconazole Nitrate Microsponge as a Topical Drug Delivery System. Indian J Pharm Sci. 77(6): 2015: 675-680.

38. Mandlik SK, Siras SS, Birajdar KR. Optimization and characterization of sertaconazole nitrate flexisomes embedded in hydrogel for improved antifungal activity. J Liposome Res. 29(1): 2019: 10-20.

39. https://patents.google.com/patent/US5135943

Received on 19.11.2019 Modified on 27.03.2020

Research J. Pharm. and Tech. 2021; 14(6):3441-3448.

DOI: 10.52711/0974-360X.2021.00599