Search

Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied. [ABSTRACT FROM AUTHOR]

In this study, an attempt was made to synthesize a new sorbent based on the second generation of silica coated magnetic poly(amidoamine) (Fe3O4@SiO2@PAMAM) to improve the performance of magnetic solid phase extraction (MSPE) of some antifungal drugs including miconazole, clotrimazole and ticonazole in various real samples such as urine and human plasma. The extracted analytes were measured by high performance liquid chromatography equipped with ultraviolet detection (HPLC-UV). Field emissionscanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and Fourier transform-infrared spectroscopy (FT-IR) were used to study the morphology and structure of the prepared sorbent. The various factors such as: extraction time, sorbent amount, solvent desorption volume, desorption time, ionic strength and pH were studied and optimized. The method was validated according to ICH guidelines with respect to precision, accuracy, linearity, specificity, robustness, and limits of detection and quantification. Under the optimized condition, the linearity of the method was in the range of 1-500 µg L-1 (miconazole= 1-200 µg L-1, clotrimazole = 1-500 µg L-1 and ticonazole = 1-200 µg L-1). The obtained coefficient of determination (r²) were between 0.9871-0.9977. The limits of detection (LODs) were also calculated to be 0.14-0.18 µg L-1 (miconazole= 0.16 µg L-1, clotrimazole = 0.18 µg L-1 and ticonazole=0.14 µg L-1). The limits of quantification (LOQs) were also in the range of 0.46-0.60 µg L-1 for the selected analytes. The relative standard deviations (RSDs%), were obtained in the range of 4.6 to 5.9%. Moreover, the calculated enrichment factors were between 85 and 93. The proposed method was employed for the analysis of various real samples such as urine and plasma samples. The obtained recoveries (higher than 92%) indicated that the method was useful and applicable in complicated real samples. [ABSTRACT FROM AUTHOR]

A reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed to analyze the simultaneous estimation of doxorubicin and clotrimazole. The method was achieved by Nucleodur C18 column with dimension 250 × 4.6 mm (5 μm) using gradient elution. The mobile phase contained 0.2% formic acid (pH 3.2) and acetonitrile. The flow rate was kept at 1.0 mL/min and detection and quantitation of both drugs (doxorubicin and clotrimazole) were achieved using a photodiode array detector at 276 nm, which was the isosbestic point for both drugs. The proposed method was validated according to the current International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use guidelines for specificity, linearity, accuracy, precision, and robustness. The developed method showed a linear response (R2 > 0.999), and was accurate (recoveries 97%–103%), precise (resolution ≤1.0%), sensitive, and specific. Thus, the developed RP-HPLC method for the simultaneous estimation of both drugs was successfully validated and can be utilized for the estimation of these drugs in the formulations being developed. [ABSTRACT FROM AUTHOR]

Background: Candidial balanitis, balanoposthitis and vulvovaginitis can be diagnosed by direct microscopy, culture and treated with antifungals. Resistance to antifungals is emerging. Hence, we conducted a study to identify the causative species and antifungal susceptibility. Aim: To observe the species differentiation and antifungal susceptibility pattern in patients with genital candidiasis. Materials and Methods: A prospective observational study was carried out that included 54 patients of age group (18‑60 years) diagnosed clinically and direct microscopically (KOH) for genital candidiasis. Culture was done using Sabouraud dextrose agar. Species identification and antifungal susceptibility were tested. Descriptive data were expressed in the form of frequency and percentage. Results: Out of 54 patients, 41 had culture positive candidiasis. Among the isolated species, 68.3% were Candida albicans (28/41) and 31.7% were non‑ albicans Candida spp. Among non‑albicans Candida species (13/41), Candida glabrata (19.5%), Candida tropicalis (7.3%), Candida guilliermondii (2.4%), Candida parapsilosis (2.4%) were identified. Antifungal susceptibility was tested for fluconazole (FLU), clotrimazole (CLTZ), itraconazole (ITZ), ketoconazole (KTZ), voriconazole (VOR), amphotericin‑B (AMPH‑B). Except C. glabrata and C.parapsilosis, all other species were sensitive to all tested antifungals. All isolated species were sensitive to KTZ, VOR, AMPH‑B, and CLTZ. Nearly 22% of isolates were resistant to fluconazole. Conclusion: C. glabrata causes complicated, severe recurrent vulvovaginitis which is fluconazole resistant. Drug sensitivity prior prescribing antifungal agent identifies appropriate drug, decreases patient’s disease morbidity and cross resistance. [ABSTRACT FROM AUTHOR]

Objective • This meta-analysis aims to assess the efficacy of combining clotrimazole and metronidazole in the treatment of mixed infectious vaginitis (VA). The goal is to provide clinical guidance for future medication strategies. Methods • We conducted a comprehensive search of the literature database for studies involving the use of clotrimazole combined with metronidazole in the treatment of mixed infectious VA. After rigorous screening, eligible studies were subjected to meta-analysis using RevMan 5.3 software. Outcome measures included cure rates, recurrence rates, and the incidence of adverse reactions. Results • Six randomized controlled trials (RCTs) were included, comprising 160 patients in the test group (treated with clotrimazole combined with metronidazole) and 160 patients in the control group (treated with alternative regimens). All selected studies were of high quality and possessed significant reference value. Metaanalysis results indicated that, in comparison to the control group, the test group exhibited a comparable incidence of adverse reactions (P > .05), higher cure rates, increased treatment satisfaction, and a lower recurrence rate (P < .05). Conclusions • The combination of clotrimazole and metronidazole is an effective treatment option for mixed infectious vaginitis, thus warranting recommendation. [ABSTRACT FROM AUTHOR]

Candida species cause systemic candidiasis in immunocompromised cancer patients. Currently, a large proportion of bloodstream infections are due to non-albicans Candida species (Candida species other than C. albicans), with Candida tropicalis and Candida parapsilosis being the most isolated Candida species from cancer patients. In this study, 52 Candida isolates were collected from cancer patient at the Apeksha Hospital, Maharagama, Sri Lanka. Molecular identification of isolated Candida samples employed a multiplex PCR technique utilizing specific primer pairs for two strains of both Candida tropicalis and Candida parapsilosis. Furthermore, to determine the susceptibility of the identified isolates, antifungal susceptibility testing was conducted using the disk diffusion method on Mueller-Hinton agar medium. Six antifungal drugs, including Fluconazole, Itraconazole, Clotrimazole, Miconazole, Ketoconazole, and Amphotericin B, were utilized in the susceptibility testing. In this study 38% of the strains were identified as Candida tropicalis II while, 31% were identified as Candida parapsilosis II. According to this study Fluconazole was the most susceptible drug against both species and Amphotericin B was the least susceptible drug. Ketoconazole, Clotrimazole, Itraconazole and Miconazole showed varying degrees of susceptibility patterns. The study concludes that multiplex PCR is a better approach for the identification of both Candida tropicalis and Candida parapsilosis for clinical and diagnostic purposes and Fluconazole is the best antifungal drug against Candida parapsilosis, while caution is advised when using Amphotericin B as a treatment option since its' low susceptible rates. [ABSTRACT FROM AUTHOR]

Alterations in ivermectin (IVM, 22,23-dihydro avermectin B1a+22,23-dihydro avermectin B1b) toxicokinetics following P-glycoprotein (P-gp) induction by clotrimazole (CTZ) were examined in rainbow trout (Oncorhynchus mykiss) to assess the potential importance of P-gp activity levels in xenobiotic distribution and kinetics in fish. Control and fish pretreated with CTZ (30 µmol/kg) were administered 175 µg/kg 3H-IVM into the caudal vasculature. At various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) following injection, tissues (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad and fat) were removed analyzed for IVM-derived radioactivity. IVM concentration declined in blood, liver, kidney and gill, and concentrations in other tissues remained constant over the sampling period. The highest measured concentrations were found in kidney, followed by liver, with the lowest values found in brain, eye and gonad. The highest % of the administered dose was found in the liver and kidney in the immediate hours post-administration, and in the intestines and fat at 24 h post-administration. P-gp induction by CTZ did not alter IVM distribution or any calculated toxicokinetic parameter (AUC, mean residence time, T1/2, clearance rate, volume of distribution), suggesting that P-gp induction may be limited or that P-gp plays a lesser role in xenobiotic kinetics in fish compared to mammals. [ABSTRACT FROM AUTHOR]

Vulvovaginitis is a prevalent gynaecological ailment worldwide, often attributed to bacteria, Candida fungi, or Trichomonas. The synergistic action of antifungal agents and essential oils can enhance the efficacy against pathogenic microorganisms. In this study, a simultaneous quantitative method for determining clotrimazole and eugenol in a laboratory-compounded gel product was developed using high-performance liquid chromatography with a photodiode array detector (HPLC-PDA). The HPLC-PDA system utilised in this study was the Shimadzu LC- 20AD, with a HiQ Sil RP C18 HS column (250 x 4.6 mm, 5 µm), and a mobile phase consisting of methanol-water in an 80:20 (v/v) ratio, employing isocratic elution at a flow rate of 1.0 ml/min. The injection volume was set at 20 µl, and detection was performed at a wavelength of 229.0 nm. The analytical procedure was validated in accordance with ASEAN guidelines for the validation of analytical procedures, successfully meeting the criteria for specificity, accuracy, system suitability, repeatability, intermediate precision, and linearity within the concentration range of 2.25 to 36.00 ppm for eugenol and 12.00 to 200.00 ppm for clotrimazole. Subsequently, this validated procedure was applied to quantify the clotrimazole and eugenol content in bulk materials and three different lots of gel products. The results for clotrimazole and eugenol content in both the raw materials and the gel product lots fell within an acceptable range, with deviations of less than ±10% compared to the labelled content.

Antifungal prophylaxis postheart transplant (HT) may include voriconazole or clotrimazole, which interact with tacrolimus. There is no guidance for tacrolimus adjustment when transitioning from voriconazole to clotrimazole; therefore, this study evaluates tacrolimus concentration/dose (C/D) ratio on voriconazole compared to clotrimazole. This retrospective, single-center analysis included HT recipients (February 2016-September 2021) who received tacrolimus and voriconazole followed by clotrimazole. Tacrolimus C/D ratio was compared on voriconazole vs clotrimazole, and on clotrimazole vs postantifungal discontinuation. Seventy-two patients were included. The median (interquartile range) tacrolimus C/D ratio was 41% (1.7-fold) lower after transition from voriconazole to clotrimazole [5.1 (3.5, 7.7) vs 3.0 (2.0, 4.6) (ng/ml)/(mg/day), p

Background: Otomycosis is a superficial mycotic infection of the external auditory canal. Clinical presentation, along with otoscopic findings, is sufficient to make the diagnosis in most of the cases. Treatment includes aural cleaning followed by the instillation of anti-fungal ear drops. In the recent years, there has been an increasing trend of antifungal resistance for the commonly used antifungals such as fluconazole and clotrimazole. Drug sensitivity patterns have also shown variability from one region to another. Aims and Objectives: To evaluate the clinico-mycological profile along with antifungal susceptibility pattern and treatment outcome of primary otomycosis. Materials and Methods: A total of 230 clinically diagnosed patients of primary otomycosis were included in this prospective study. Microbiological causes were evaluated by KOH wet mount and culture of samples collected from external auditory meatus using sterile swabs. Fungal culture was done on Sabouraud dextrose agar with chloramphenicol at 25°C and 37°C. Anti-fungal susceptibility test was done by disk diffusion method using medium Muller-Hilton agar with glucose and methylene blue. All the patients were treated with the removal of fungal debris with topical clotrimazole instillation and were followed up after 7 days. Non-responders were treated with topical itraconazole. Results: Male-to-female ratio in study participants was 1:1.3. The most frequently observed risk factor was the instillation of oil in the ear (20%). Ear itching was the commonest symptom (70.9%). Positive fungal growth was seen in 203 (88.3%) cases. Aspergillus was present in 185 (91.1%) cases, followed by Candida in 18 (8.9%) cases. Voriconazole had the highest sensitivity followed by itraconazole. 167 (83.3%) patients responded to primary treatment (topical Clotrimazole), 36 (16.7%) patients were non-responders. Conclusion: All the clinically suspected patients should be evaluated for fungal positivity, which may further guide in the selection of appropriate anti-fungal agents. Awareness regarding the predisposing factors for otomycosis in the general population may result in a significant drop in the incidence of otomycosis.

Introduction: Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of amphotericin B, its potential for PV treatment warrants investigation. Objectives: This study aimed to compare the efficacy of topical liposomal amphotericin B and clotrimazole cream in treating PV. Methods: A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years, who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all patients through positive microscopic results. The amphotericin group received topical gel containing liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole 1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment. Results: Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant difference between the groups in terms of the degree of cure (P=0.75). Adjustments for age, sex, lesion extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete cure rate (P>0.05). Conclusions: The topical application of liposomal amphotericin B 0.4% is equally effective as topical clotrimazole 1% in treating pityriasis versicolor. These findings suggest that liposomal amphotericin B could be considered as a viable alternative treatment for PV. Further research is warranted to explore its long-term consequences and safety profile.

Background: Otomycosis is infection caused by fungi in the external auditory canal and is frequently diagnosed by clinical presentation. There was no common agent in treating otomycosis even though many studies were conducted to conclude the effective antifungal agent. Aim: This study was conducted to compare rate of improvement of otomycosis treatment with topical medications such as clotrimazole and acetic acid wash. Materials and Methods: This study was conducted in 100 patients during the period of June 2022 to June 2023. After receiving the ethical committee approval, this study was initiated. All the patients were included in the study who were referred to ENT Department Malla Reddy Institute of Medical Sciences Hyderabad. A group (Group A) of patients were treated after cleaning the ear canal with suction with 8 drops of 1% clotrimazole (ear drop) each 8 h. Other group (Group B) of patients were treated with acetic acid wash. Results: Males (56) were more than females (44) in the present study. Aspergillus Spp were observed in 60 patients and Candida Spp were observed in 40 patients. Recurrence after 14 days in group B was 4% and in group A was 6%. Between two groups, no significant difference was observed in rate of recurrence (P=0.71). Recurrence after 21 days in group B was 8% and in group A was 6%. Between two groups, no significant difference was observed in rate of recurrence (P=0.76). Duration of treatment in group-B is significant when compared to others. Conclusion: Both clotrimazole and acetic acid have shown similar therapeutic efficacy in otomycosis treatment however, acetic acid is better suggested to be opted due to its significantly shorter duration of treatment and to reduce the indiscriminate use of antibiotics. [ABSTRACT FROM AUTHOR]

Drug resistance of pathogenic candidal strains to conventional antifungal agents represents a significant health issue contributing to high morbidity worldwide. Hence, the aim of the current study focused on evaluating the antifungal and synergistic activities of the green synthesized zinc oxide nanoparticles formulated using Laurus nobilis leaf extract. The biogenic ZnONPs were hexagonal in shape with average particle size diameter of 37.98 nm and pure crystalline structure as detected by XRD data. The highest antifungal activity of biogenic ZnONPs was detected against Candida parapsilosis strain demonstrating relative inhibitory zone diameters of 17.13 ± 0.74 and 25.78 ± 0.47 mm, at the concentrations of 100 and 200 µg/disk, respectively. Moreover, the biogenic ZnONPs demonstrated the highest synergistic activity with clotrimazole antifungal agent against Candida glabrata followed by Candida auris strains. MTT assay revealed that the biogenic ZnONPs showed low toxicity demonstrating relative IC50 value of 774.45 µg/mL against normal lung fibroblast cells which further affirmed their biosafety for application. In conclusion, the bioinspired ZnONPs could be utilized for the formulation of effective antifungal agents against drug resistant candidal strains and also could be combined with antifungal agents to boost their antifungal efficiency. [ABSTRACT FROM AUTHOR]

This study reports the isolation of the yeast Saccharomyces cerevisiae Dag-1 (OQ107063.2) from the seawater of the Caspian Sea, specifically from the coastal territory of the Samursky Reserve, Republic of Dagestan, Russia. The strain’s diagnostic and genetic characteristics are provided. Morphological features of the S. cerevisiae Dag-1 include round cells measuring 5.0×5.0 and 1.0×1.0 µkm in size. On Sabouraud’s media, it forms round, convex, opaque, creamy, glossy colonies with a diameter of 3-5 mm. The isolated strain demonstrates the ability to thrive in seawater with a salinity ranging from 12.8-13.0‰, across various temperature ranges (0 –+10, 23- 28, 35-40, 30-37°C), and under different pH conditions (5.6; 8.4-8.5). Additionally, it utilizes monomeric sugars (L-glucose, D-mannose, D-sucrose, D-arabinose, D-cellobiose, and D-xylose) as a source of carbon and energy, also metabolizing alcohols such as D-sorbitol, D-mannitol, and Dinositol (vitamin B8). The strain does not absorb the amino acids lysine and ornithine, and it is catalase-, amylase-, and β-glucosidase-positive while being urease-, oxidase-, and β-galactosidasenegative. Moreover, the strain exhibits high sensitivity to the antibiotics of ketoconazole, nystatin, clotrimazole, fluconazole, and itraconazole. Resistance is observed against the inhibitor potassium tellurite and pathogenic bacteria Escherichia coli, Staphylococcus aurens, and Klebsiella oxitoka. These findings contribute to expanding our understanding of the ecological distribution of marine yeasts and the isolation of an S. cerevisiae strain possessing characteristics of industrial microorganisms. [ABSTRACT FROM AUTHOR]

Objective: In vitro and in vivo researches have shown that silver nanoparticles have more antimicrobial properties with a lower concentration than antifungal agents against candida vaginitis. Therefore, this study evaluated the therapeutic effect of silver nanoparticles (Nivasha spray15ppm) compared to clotrimazole 1% vaginal cream on candida vaginitis. Materials and methods: In this clinical trial study, 110 women with confirmed candida vaginitis randomly were divided into test (n=58) and control (n=52) groups. Silver nanoparticles spray with an applicator (Nivasha 15 ppm), and clotrimazole 1% were administered to test and control groups, respectively. Then, within ten days, post-intervention checkup and patient self-reported for treatment results were recorded in checklists and the data were analyzed statistically. Results: The improvement rate in test group (98.0%) was 1.44 times higher than in control (67.9%). Moreover, disease symptoms after the intervention (including unusual secretions, itching and burning, redness) in test group were significantly less than in the control, but there was no significant difference in the ratio of edema in two groups )p=0.071(. Furthermore, the average recovery time (days) of all symptoms in test group was lower than control (p<0.05). Finally, the rate of patients' satisfaction with the treatment process in the test group (76.9%) was more than control (46.6%) (p=0.004). Conclusion: Nivasha spray had more effectiveness compared to the clotrimazole 1%. Therefore, it can be used as an alternative drug in the treatment of Candida vaginitis. [ABSTRACT FROM AUTHOR]

Copyright of Diyala Journal of Medicine is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many studies highlighted the importance of the IK channel for the proliferation and the migration of different types of cancer cells, showing how IK blockers could slow down cancer growth. Based on these data, we wanted to characterize the effects of IK blockers on melanoma metastatic cells and to understand if such effects were exclusively IK-dependent. For this purpose, we employed two different blockers, namely clotrimazole and senicapoc, and two cell lines: metastatic melanoma WM266-4 and pancreatic cancer Panc-1, which is reported to have little or no IK expression. Clotrimazole and senicapoc induced a decrease in viability and the migration of both WM266-4 and Panc-1 cells irrespective of IK expression levels. Patch-clamp experiments on WM266-4 cells revealed Ca2+-dependent, IK-like, clotrimazole- and senicapoc-sensitive currents, which could not be detected in Panc-1 cells. Neither clotrimazole nor senicapoc altered the intracellular Ca2+ concentration. These results suggest that the effects of IK blockers on cancer cells are not strictly dependent on a robust presence of the channel in the plasma membrane, but they might be due to off-target effects on other cellular targets or to the blockade of IK channels localized in intracellular organelles. [ABSTRACT FROM AUTHOR]

Polymers, including non-linear copolymers, have great potential in the development of drug delivery systems with many advantages, but the design requires optimizing polymer–drug interactions. Molecular dynamics (MD) simulations can provide insights into polymer–drug interactions for designing delivery systems, but mimicking formulation processes such as drying is often not included in in silico studies. This study demonstrates an MD approach to model drying of systems comprising either hydrophilic tinidazole or hydrophobic clotrimazole drugs with amphiphilic hyperbranched copolyethers. The simulated drying protocol was critical for elucidating drug encapsulation and binding mechanisms. Experimentally, two polymers were synthesized and shown to encapsulate clotrimazole with up to 83% efficiency, guided by interactions with the hydrophobic core observed in simulations. In contrast, tinidazole is associated with surface regions, indicating capacity differences between drug types. Overall, this work highlights MD simulation of the drying process as an important tool for predicting drug–polymer complex behaviour. The modelled formulation protocol enabled high encapsulation efficiency and opened possibilities for the design of delivery systems based on computationally derived binding mechanisms. This demonstrates a computational–experimental approach where simulated drying was integral to elucidating interactions and developing optimized complexes, emphasizing the value of molecular modelling for the development of drug delivery formulations. [ABSTRACT FROM AUTHOR]

The October 2022 draft United States Food and Drug Administration (FDA) guidance presents an option of in vitro release test (IVRT) studies as a biowaiver for topical drug products submitted in abbreviated new drug applications (ANDAs). However, the product-specific guidance (PSG) for 1% clotrimazole (CLZ) topical cream does not provide an in vitro option for biowaiver and requires a clinical endpoint study to demonstrate bioequivalence (BE). Therefore, the main objective was to use IVRT to investigate pharmaceutical equivalence of several 1% CLZ topical creams from two countries — South Africa (SA) and Canada. This investigation aims at demonstrating the utility of IVRT to determine 'sameness' and/or differences between topical creams containing 1% CLZ and the potential of IVRT for supporting biowaivers, thereby obviating the necessity to conduct clinical endpoint studies in patients. A validated IVRT method was applied to conduct comparative IVRT runs on five generic products marketed in SA and one Canadian generic, which were compared against a relevant comparator product from their country of origin in accordance with the FDA's acceptance criteria of 75–133.33%. All five SA-marketed generic creams showed pharmaceutical inequivalence to the SA comparator product indicating Q1/Q2/Q3 differences. Despite containing the same excipients as both comparator products, the Canadian generic showed substantially lower release rate compared to the comparator products which could be attributed to Q2/Q3 differences. The IVRT method displayed the requisite ability to assess the various 1% CLZ creams and confirmed the potential of the IVRT method to support a biowaiver for 1% CLZ topical creams. [ABSTRACT FROM AUTHOR]

Introduction and aim: Otomycosis, a superficial fungal infection, is usually associated with frequent exposure to water, and trauma to the external auditory canal. We aimed to establish that topical application of 1% clotrimazole cream only once is a cost-effective and efficient treatment option for otomycosis. Methods: The external auditory canal of each patient was cleaned by suction under the microscope. Followed by filling with 1% clotrimazole cream using a green cannula and a 10 ml syringe. Patients were followed up a week later. Results: Among the 93 patients enrolled in the study, at the first visit > 81% of patients reported itching or otalgia while 43% reported aural fullness. On examination, 92.5% of patients had fungal hyphae while 58.1% of patients had erythema. At follow-up 1-week later, >90% of patients reported relief from itching, otalgia and aural fullness and had no hyphae. Among patients with erythema, only 9% had not recovered from it completely at follow-up. Conclusion: We report the topical application of 1% clotrimazole cream only once is a cost-effective and efficient treatment for otomycosis. By this method treatment failures of otomycosis due to a patient's unwillingness in applying topical drops routinely for a long time can be avoided. [ABSTRACT FROM AUTHOR]

• The mean itching, dyspareunia, and dysuria score improved using CLOT-M cream. • Longer response of non-albicans Candida strains to CLOT-M cream. • CLOT-M group showed significant yeast culture improvement in 2nd follow-up visit. Vulvovaginal candidiasis is a common gynecologic infection, and recurring cases are yet incurable. This trial was based on Persian medicine to compare how effective marshmallow aqueous extract 4% plus clotrimazole 1% (CLOT-M) is compared to clotrimazole 1% vaginal creams on VVC. This study randomly assigned 100 women with VVC into two groups. The target group (n = 50) was treated with CLOT-M while controls (n = 50) with clotrimazole vaginal creams for seven consecutive nights. Different VVC symptoms and signs, and yeast culture from vaginal discharge were evaluated as the outcome measures before the intervention and 7 and 30 days after. The efficacy of CLOT-M vaginal cream was assessed during the 1st and 2nd follow-ups, indicating a significant decrease in mean itching (P = 0.001 for both comparisons) and dyspareunia score (P = 0.001 and P = 0.04, respectively) as compared to treatment with clotrimazole vaginal cream. Moreover, after 7 days of the intervention, patients in the CLOT-M group experienced significant improvement in mean dysuria score compared to those in the control group (P = 0.001). Neither cream caused any significant adverse events. It seems that CLOT-M vaginal cream had a significant effect on the VVC symptoms improvement, without any significant side effects. However, larger sample-sized trials are needed for more evidence-based judgment. [ABSTRACT FROM AUTHOR]

During the interaction of aqueous-ethanol or ethanol solutions AgNO3, H[AuCl4], and CuCl2, as well as aqueous suspensions of slightly soluble copper(II) salts Cu(C6H4NO2)2·H2O, Cu(C7H5O2)2∙3H2O, and CuC7H4O3∙H2O with the ethanol solution of clotrimazole at pH of ~(5.0–5.5), the [Ag(C22H17ClN2)2]NO3·2H2O, [Au(C22H17ClN2)Cl3], [Cu(C22H17ClN2)2Cl2]·5H2O, Cu(C22H17ClN2)4(C6H4NO2)2, Cu(C22H17ClN2)4(C7H5O2)2, and Cu(C22H17ClN2)3(C7H4O3)·2H2O compounds are synthesised. They are characterised by elemental, thermal, thermogravimetric, and IR spectroscopic methods of analysis. The [Ag(C22H17ClN2)2]NO3·2H2O complex was shown to have a higher antimycotic activity against Saccharomyces cerevisiae fungi than that of AgNO3 and C22H17ClN2. Cocrystals/salts of the composition C22H17ClN2·C6H5NO2, C22H17ClN2·C7H6O2, 2C22H17ClN2·C7H6O3, and 2C22H17ClN2·C19H19O6N7·H2O are obtained from aqueous and aqueous ethanol suspensions containing nicotinic, benzoic, salicylic, and folic acids and clotrimazole (pH is 4.5–6.0). These cocrystals and salts were studied usin thermogravimetric, IR-spectroscopic methods. Diffraction patterns of the powders were obtained. The influence of the difference in the pKa components on the ability to form cocrystals/salts was assessed. [ABSTRACT FROM AUTHOR]

Introduction: Reactive sulphur species (RSS) have been recently discovered to be a part of a major endogenous antioxidant system. Nonetheless, the RSS was implicated as an underlying mechanism in reducing the efficacy of several antibiotics, such as penicillin and carbapenem. The emergence of drug resistance has been a global concern. In fact, several incidences on the azole resistant Trichophyton sp. isolates in the clinical setting, such as clotrimazole, have also been reported. Clotrimazole is a broad-spectrum antifungal commonly used in dermatophytosis management caused by the Trichophyton, Epidermophyton, and Microsporum genera. This study investigated the role of RSS, as a potential element underlying the resistance against clotrimazole. Methods: The Trichophyton rubrum growth in sulphide-rich environment was initially established by exposing towards several concentrations of sodium hydrosulphide (NaHS). Then, to investigate the potential interaction between the RSS and clotrimazole, the T. rubrum were treated with 1000 µM of clotrimazole, with or without co-treatment several concentrations of NaHS. Broth microdilution method was performed to observe the growth of the fungus. Results: As expected, clotrimazole exhibited cytotoxic effect towards T. rubrum at high concentration. Interestingly, the growth of T. rubrum was significantly recovered (p<0.01) in samples co-treated with clotrimazole (1000 µM) and NaHS in a dose-dependent manner. Co-treatment with the highest concentration of NaHS (1000 µM), the T. rubrum growth was recorded approximately 90%, despite being exposed to 1000 µM of clotrimazole. Conclusion: In conclusion, RSS potentially interferes with the efficacy of clotrimazole. The exact mechanism underlying such activity warrants further investigation. [ABSTRACT FROM AUTHOR]

• An analytical discussion of potential of lichen substances against yeast species. • Lichen substances cause varying degree of inhibition of yeast growth. • Some of commercial antibiotics can be replaced by potential of lichen substances. • Possibilities of using lichen substances as new application means in pharmacy or cosmetics industry. A meta-analysis of literature data with statistical analysis concerning the effect of lichen substances on the inhibition of 10 yeast species (Candida albicans, C. dubliniensis, C. glabrata, C. parapsilosis, C. sake, C. tropicalis, Colacogloea diffluens, Cryptococcus neoformans, Issatchenkia orientalis and Saccharomyces cerevisiae) is provided. Lichen extracts were obtained using 16 solvents from 100 epiphytic, 51 epigeic and 37 epilithic lichen species. The most studied lichen taxa at the generic level belonged to the family Parmeliaceae. 67 individual secondary metabolites belonging to 12 biochemical classes were subjected to experiments. The MIC was used most frequently. Candida albicans was the most commonly tested species; other fungal species remain relatively less or very poorly tested. Against C. albicans , a stronger antifungal potential is demonstrated by extracts from numerous lichen species, including Evernia prunastri, Hypotrachyna vexans, Pseudevernia furfuracea, Ramalina pollinaria, R. polymorpha, Cladonia foliacea, C. pocillum, C. rangiformis and Umbilicaria cylindrica , which generated secondary compounds such as atranorin, α-collatolic acid, ethyl everninate, lecanoric acid, methyl 2,6-dihydroxy-4-methylbenzoate, protolichesterinic acid, retigeric acid A and B, scrobiculin and usnic acid. The potential of the extracts and secondary metabolites makes it possible to replace several commercial antibiotics in the future, in particular clotrimazole and fenticonazole. For the purpose of future experiments, this review stresses the need to standardizse research methodology, especially for the simultaneous determination of MIC and IZ and, if possible, MFC. There is a need for greater use of water as a solvent to extract lichen substances as a safe and feasible method for phytopharmaceutical and cosmetic purposes. The conclusions drawn highlight the prospective use of lichen extracts and secondary metabolites against yeast in the medical, phytopharmaceutical and cosmetic fields and as preservatives. [ABSTRACT FROM AUTHOR]

This article discusses a study that evaluated the antifungal activity of nano-curcumin against Candida species, which cause otomycosis, a fungal infection of the ear. The study found that nano-curcumin showed some antifungal activity against Candida, but it was less effective than commonly used antifungal drugs. However, due to its safety profile, nano-curcumin could be considered as a potential treatment option for otomycosis with further research. The study was conducted in Iran and approved by the Research Ethics Committee of Babol University of Medical Sciences. [Extracted from the article]

Coordination compounds featuring one or more antifungal azole (AA) ligands constitute an interesting family of candidate molecules, given their medicinal polyvalence and the viability of drug complexation as a strategy to improve and repurpose available medications. This review reports the work performed in the field of coordination derivatives of AAs synthesized for medical purposes by discussing the corresponding publications and emphasizing the most promising compounds discovered so far. The resulting overview highlights the efficiency of AAs and their metallic species, as well as the potential still lying in this research area. [ABSTRACT FROM AUTHOR]

Background and Purpose: This review aimed to compare the efficacy of acidifying agents and clotrimazole in the treatment of patients with otomycosis.Materials and Methods: The databases, including Research Gate, Google Scholar,ScienceDirect, Embase, Medline, Scopus, Cochrane, and library databases of clinical trials were searched in this study. The keywords were "Fungal Ear Infection" and "Otitis External" for otomycosis, "Clotrimazole", Lotrimin", "Mycelex", "Desenex", and "Clotrimaderm Mycoderm" for clotrimazole, and "Boric Acid Alcohol", "Alcohol-vinegar solution", Burow solution (Domeboro), "Isopropyl Alcohol", "VoSol" and "Acetic Acid" for acidifying agents. Regarding search strategy, a total of 53 studies were collected, 11 of which were maintained for assessment. Almost all studies were published after 1990. These articles discussed the role of clotrimazole and acidifying compounds in the treatment of otomycosis. Moreover, the route of administration, dosage, and side effects of these medications were highlighted.Results: Eight studies had similar results and claimed that clotrimazole has the best or most significant effect on the treatment of otomycosis for patients suffering from pain,itching, swelling, and hearing loss.Conclusion: Although all medications appear effective, there is a paucity of evidence to fully support the decision to choose between clotrimazole or acidifying agents for the treatment of otomycosis in terms of both efficacy and safety. However, in the biomedical field, the re-emerging investigation attention is due to the statements of a number of mechanisms defending the use of acidifying agents to treat mycosis (of antifungal-resistant species).

Introduction: The intravaginal drug administration enables treatment of the local and systemic diseases. The anatomy and physiology of a vagina provide several difficulties for drug technologists due to the small amount and continuous production of vaginal discharge, especially in the case of lipophilic drugs often characterized by insufficient solubility. The application of poorly soluble drug substances in the form of nanoemulsions improves their availability. However, in the case of nanoemulsion-based vaginal dosage forms, no standardized methods have been defined for testing the amount of a drug released from encapsulated form. Aim of the study: Comparison and development of a method for testing the availability of active pharmaceutical substances from vaginal nanoemulsion-based drug forms. Materials and methods: The nanoemulsion and reference products (cream and suspension) were placed in a dialysis bag separating them from the acceptor medium. The changes in the concentration of the free fraction of the model active substance – clotrimazole were assessed. The experiments were performed using 2 static methods of different mixing method (magnetic stirring and USP apparatus III) and 2 dynamic methods including the flow of the medium through the flow-through cell at 2 mL/min and 2 mL/h. The experiments were conducted for 5 h. Results: Incomplete release of the active pharmaceutical ingredient was observed for all tested formulations over the experiment. Despite the delivery of a fresh portion of the medium, low concentrations of the free clotrimazole fraction were observed for both flow-through methods i.e., a maximum of about 7.5% of the dose for the 2 mL/min flow rate and 5% for the 2 mL/h flow rate. In stationary methods, the maximum recorded concentrations of the free fraction of the drug corresponded to approx. 25% of the initial amount. For the pilot stationary method, high standard deviations (SD) were observed, which affected the low discriminatory properties of the method. The method based on the reciprocating cylinder dissolution apparatus provided results exhibiting smaller SD and more significant differences between the tested formulations. The highest concentrations among the evaluated formulations were observed for nanoemulsion or nanoemulsion and suspension, depending on the used test technique. Significantly lower doses of the drug were released from the cream in almost every test. Conclusions: The selection of the method used to assess the pharmaceutical availability of an active pharmaceutical ingredient has a crucial impact on the release profiles obtained. The stationary method using a reciprocating cylinder apparatus (USP apparatus III) had the highest measurement precision and provided the most discriminatory results.

Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.

Objective: In vitro and in vivo researches have shown that silver nanoparticles have more antimicrobial properties with a lower concentration than antifungal agents against candida vaginitis. Therefore, this study evaluated the therapeutic effect of silver nanoparticles (Nivasha spray15ppm) compared to clotrimazole 1% vaginal cream on candida vaginitis. Materials and methods: In this clinical trial study, 110 women with confirmed candida vaginitis randomly were divided into test (n=58) and control (n=52) groups. Silver nanoparticles spray with an applicator (Nivasha 15 ppm), and clotrimazole 1% were administered to test and control groups, respectively. Then, within ten days, post-intervention checkup and patient self-reported for treatment results were recorded in checklists and the data were analyzed statistically. Results: The improvement rate in test group (98.0%) was 1.44 times higher than in control (67.9%). Moreover, disease symptoms after the intervention (including unusual secretions, itching and burning, redness) in test group were significantly less than in the control, but there was no significant difference in the ratio of edema in two groups) p=0.071(. Furthermore, the average recovery time (days) of all symptoms in test group was lower than control (p