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Griseofulvin (GF), which is mainly extracted from Penicillium griseofulvum, is a heat-resistant, chlorine-containing non-polyene antifungal antibiotic. Previous research shows that GF has a variety of pharmacological effects, such as antiinflammatory, antifungal, antiviral, and antitumor effects. In recent years, GF has received extensive attention for its antitumor effects as a natural compound, offering a low price, a wide range of uses, and other beneficial characteristics. However, no comprehensive review of GF pharmacological activity in tumors has been published so far. In order to fully elucidate the antitumor activities of GF, this review focuses on the antitumor potential and toxicity of GF and its derivatives, based on a literature search using PubMed, Web of Science, and other databases, to lay a good foundation for further research of GF and the development of new drugs for antitumor activities. [ABSTRACT FROM AUTHOR]

The current investigation focuses on producing zinc oxide nanoparticles (ZnO NPs) utilizing a quick, economical, and environmentally friendly approach employing aqueous fruit extracts of Dysoxylum binectariferum plant. The ZnO NPs were thoroughly characterized using P‐XRD, FTIR, SEM, EDS, and BET techniques. The synthesized nanoparticles' anti‐bacterial properties were evaluated against Gram‐negative bacteria (E. coli and P. aeruginosa) and Gram‐positive bacteria (S. aureus and S. pyogenes). The findings indicated that the synthesized material exhibited greater efficacy against Gram‐negative bacterial infections, especially E. coli. Furthermore, the anti‐fungal activity was examined using the C. albicans strain, demonstrating that the synthesized ZnO NPs were twice as effective against C. albicans compared to the conventional medication Griseofulvin. In contrast, Griseofulvin, with a 500 μM MIC against the C. albicans pathogenic fungal strain, did not display the same level of efficacy. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis, a prevalent fungal infection, often exhibits treatment failure. It poses ongoing public health concerns, urging exploration of alternative treatment strategies. This study examines eucalyptol's in vitro activity and its interaction with antifungal agents against dermatophyte isolates. Methods: Overall, 489 patients clinically suspected of dermatophytosis were investigated, and the causative agents were molecularly identified. The antifungal activity of eucalyptol, itraconazole, terbinafine, and griseofulvin was assessed according to the guideline of the Clinical and Laboratory Standards Institute (CLSI M38 ed3). The interaction between eucalyptol and the aforementioned antifungals was determined using a checkerboard method. Results: Dermatophytosis was confirmed in 30 out of 489 (6.13%) patients, with a female-to-male ratio of 3:2 and an age range of 8–67 years. The most commonly observed clinical manifestation was tinea corporis (34.21%), and Trichophyton indotineae (n = 14, 46%) was the most common causative agent. Antifungal susceptibility testing revealed that eucalyptol exhibited antidermatophyte properties with minimum inhibitory concentrations (MIC) ranging from 0.78 to 25 mg/mL. Itraconazole demonstrated the lowest geometric mean (GM) value (MIC range: 0.0019–0.25 µg/mL, GM: 0.015 µg/mL), while griseofulvin exhibited the highest GM value (MIC range: 0.125–8 µg/mL, GM: 2.37 µg/mL). The in vitro interaction of eucalyptol with antifungal drugs, except for its combination with terbinafine against two Trichophyton tonsurans isolates resulting in synergistic effects, showed indifference (n = 70, 77.77%) and antagonistic types (n = 18, 20%). Conclusion: Among the evaluated antifungals, itraconazole demonstrated the highest effectiveness against clinical isolates, while eucalyptol alone exhibited a more pronounced effect than when combined with antifungal agents. [ABSTRACT FROM AUTHOR]

Acremonium and the recently separated acremonium-like genera, such as Sarocladium, are emerging causes of opportunistic disease in humans, mainly post-traumatic infections in immunocompetent hosts, but also invasive infections in immunocompromised patients, such as those undergoing transplantation. Acremonium egyptiacum has emerged as the major pathogenic Acremonium species in humans, implicated mainly in nail but also in disseminated and organ specific infections. In this first study of acremonium-like clinical isolates in Greece, 34 isolates were identified and typed by sequencing the internal transcribed spacer, and their antifungal susceptibility was determined by a modified CLSI standard M38 3rd Edition method for filamentous fungi. A. egyptiacum was the primary species (18 isolates) followed by Sarocladium kiliense (8), Acremonium charticola, Gliomastix polychroma, Proxiovicillium blochii, Sarocladium terricola, Sarocladium zeae, and Stanjemonium dichromosporum (all with one isolate). Two isolates, each with a novel ITS sequence, possibly represent undescribed species with an affinity to Emericellopsis. All three A. egyptiacum ITS barcode types described to date were identified, with 3 being the major type. Flutrimazole, lanoconazole, and luliconazole presented the lower minimum inhibitory concentration (MIC) values against A. egyptiacum, with a geometric mean (GM) MIC of 2.50, 1.92, and 1.57 μg/mL, respectively. Amphotericin B, itraconazole, posaconazole, voriconazole, terbinafine, amorolfine, and griseofulvin MICs were overall high (GM 12.79–29.49 μg/mL). An analysis of variance performed on absolute values showed that flutrimazole, lanoconazole, and luliconazole were equivalent and notably lower than those of all the other drugs tested against A. egyptiacum. Antifungal susceptibility of the three different A. egyptiacum genotypes was homogeneous. Overall, the high MICs recorded for all systemically administered drugs, and for some topical antifungals against the tested A. egyptiacum and other acremonium-like clinical isolates, justify the routine susceptibility testing of clinical isolates. [ABSTRACT FROM AUTHOR]

Long‐acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre‐exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug–drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant co‐medications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. The Liverpool HIV interaction database was also reviewed (https://www.hiv-druginteractions.org/checker). LAI cabotegravir and rilpivirine have half‐lives of 6–12 and 13–28 weeks, respectively. Cabotegravir is primarily metabolized by UDP‐glucuronyltransferase (UGT)‐1A1 and rilpivirine by cytochrome P450 (CYP)‐3A4. LAI cabotegravir and rilpivirine themselves exhibit low risk of perpetrating interactions with co‐medications as they do not induce or inhibit the major drug metabolizing enzymes. However, they are victims of DDIs relating to the induction of their metabolizing enzymes by concomitantly administered medication. Noteworthy contraindicated co‐medications include rifamycins, carbamazepine, phenytoin, flucloxacillin and griseofulvin, which induce CYP3A4 and/or UGT1A1, causing clinically significant reduced concentrations of rilpivirine and/or cabotegravir. In addition to virologic failure, subtherapeutic concentrations resulting from DDIs can lead to emergent drug resistance. Clinicians should be aware of potential DDIs and counsel people receiving LAI cabotegravir/rilpivirine appropriately to minimize risk. [ABSTRACT FROM AUTHOR]

A series of new 7‐{3‐[3‐(Benzylidene‐amino)‐[1,2,4]triazole‐1‐yl]‐propoxy}‐4‐methyl‐chromen‐2‐one molecular hybrids 7(a–k) were synthesized using molecular hybridization approach. The synthesized new benzylidene‐triazole tethered coumarin molecular hybrids were characterized by spectroscopic studies and elemental analysis. The coumarin molecular hybrids have been explored for their antifungal efficacy in terms of tubulin inhibitors using molecular modelling studies against tubulin alphabeta hetero dimer protein. The results clearly demonstrated strong binding affinity of coumarin molecular hybrids with indole substituted and 2,4‐dihydroxy substituted as antagonists with respective binding scores of −10.5 and −10.7 kcal/mol towards tubulin alphabeta hetero dimer protein which was higher in comparison to standards griseofulvin (−8.2 kcal/mol) and fluconazole (−8.1 kcal/mol). In addition, broth dilution method was used to conduct in‐vitro antifungal studies against three fungal strains namely Candida albicans, Aspergillus niger and Aspergillus fumigatus. The results obtained clearly illustrate the antifungal activity of indole and 2,4‐dihydroxy substituted compounds which are consistent with docking simulations. Out of all the synthesized molecular hybrids, indole and 2,4‐dihydroxy substituted compounds depict outstanding antifungal activity with Minimum Inhibitory Concentration (MIC) value of 31.25 μg/ml and 62.5 μg/ml towards C.albicans and with MIC value of 31.25 for both these molecules towards A.niger in each case which is quite higher than griseofulvin and fluconazole respectively. Present work clearly demonstrates the potential efficacy of synthesized indole and 2,4‐dihydroxy substituted coumarin molecular hybrids to be considered as lead compounds for the development of new agents against resistant strains for the treatment of fungal infection. [ABSTRACT FROM AUTHOR]

Background: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. Objectives: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). Methods: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. Results: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard‐to‐treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. Conclusion: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness. [ABSTRACT FROM AUTHOR]

Solid crystalline suspensions (SCSs) containing submicron particles were introduced as a competitive solution to increase dissolution rates and the bioavailability of poorly water-soluble drugs. In an SCS, poorly water-soluble drug crystals are finely dispersed in a hydrophilic matrix. Lately, melt milling as an adapted wet milling process at elevated temperatures has been introduced as a suitable batch manufacturing process for such a formulation. In this work, the transfer from batch operation to a two-step continuous process is demonstrated to highlight the potential of this technology as an alternative to other dissolution-enhancing methods. In the first step, a powder mixture of a model drug (griseofulvin) and a carrier (xylitol) is fed to an extruder, where a uniform suspension is obtained. In the second step, the suspension is transferred to a custom-built annular gap mill, where comminution down to the submicron region takes place. The prototype's design was based on batch grinding results and a narrow residence time distribution, intended to deliver large quantities of submicron particles in the SCS. The throughput of the mill was found to be limited by grinding media compression. By inclining the mill at an angle, the grinding media position was manipulated, such that compression was avoided. Different states of the grinding media in the grinding chamber were identified under surrogate conditions. This strategy allows the maintenance of an energy-optimized comminution without adaption of the associated process parameters, even at high throughputs. Using this new process, the production of an SCS with 80–90 % submicron particles in a single passthrough was demonstrated. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis is a prevalent superficial infection caused by filamentous fungi, primarily affecting the skin and/or its appendages. In recent years, there has been a notable increase in mycotic strains resistant to standard antifungal therapies, including Trichophyton indotineae, a dermatophyte of the Trichophyton mentagrophytes complex. This review aims to provide a comprehensive overview of the treatment options for T. indotineae, elucidating their effectiveness in managing this challenging mycotic infection. Methods: For this review, a search was conducted in the PubMed, Scopus, Web of Science, Embase, and Google Scholar databases, encompassing all published data until March 2024. English-language articles detailing therapy outcomes for patients confirmed to be affected by T. indotineae, identified through molecular analysis, were included. Results: Itraconazole was shown to be a good therapeutic choice, particularly when administered at a dosage of 200 mg/day for 1–12 weeks. Voriconazole was also demonstrated to be effective, while terbinafine exhibited a reduced response rate. Griseofulvin and fluconazole, on the other hand, were found to be ineffective. Although topical treatments were mostly ineffective when used alone, they showed promising results when used in combination with systemic therapy. Mutational status was associated with different profiles of treatment response, suggesting the need for a more tailored approach. Conclusions: When managing T. indotineae infections, it is necessary to optimize therapy to mitigate resistances and relapse. Combining in vitro antifungal susceptibility testing with mutational analysis could be a promising strategy in refining treatment selection. [ABSTRACT FROM AUTHOR]

The isobaric condensed-phase heat capacities of selected pharmaceutical active ingredients (APIs), namely nifedipine (CAS RN: 21829-25-4), griseofulvin (CAS RN: 126-07-8), probucol (CAS RN: 23288-49-5) and 5,5-diphenylhydantoin (CAS RN: 57-41-0), were determined over a wide temperature range starting from 2 K by combination of relaxation (heat pulse) calorimetry, Tian-Calvet calorimetry and power-compensated differential scanning calorimetry. Heat capacity measurements were taken for clearly specified polymorphs, a liquid phase (including subcooled liquid) and a glassy amorphous phase, if feasible. For 5,5-diphenylhydantoin, a heat capacity anomaly was detected in the temperature range 160 to 190 K and interpreted based on additional calorimetric and temperature-variable crystallographic measurements as a sequence of two phase transitions, which are reported for the first time in this work. Based on the determined phase behavior and heat capacity data from near 0 K, standard thermodynamic functions for crystalline and liquid phases were calculated for all APIs studied. This work significantly extends the availability of reliable heat capacity data and related thermodynamic properties for APIs required for modeling their solubility and other applications involving thermodynamic modeling. [ABSTRACT FROM AUTHOR]

This study aims to investigate the fracture, molecular mobility and crystallization behaviors of amorphous griseofulvin (GSF) in the presence of polyvinylpyrrolidone (PVP). In the presence of 10%(w/w) PVP K90, the fracture resistance of griseofulvin was greatly improved. Compared with the pure GSF system, the average fracture temperature of the griseofulvin–PVP K90 system was decreased to approximately −6.1°C. More importantly, a statistical study revealed that the direct connection between fracture and nucleation of griseofulvin was weakened in the presence of PVP K90. This study also explored the effects of PVP K90 on the molecular dynamics and crystallization behaviors of amorphous GSF. In the presence of PVP K90, the crystal growth kinetics and molecular dynamics were both slowed down. Interestingly, needle‐like crystal growth was observed, exhibiting approximately the same rates as the bubble‐induced process. These findings are important for understanding the complex mechanisms of physical stability of polymer‐based amorphous solid dispersions. [ABSTRACT FROM AUTHOR]

Purpose: The goal was to assess, for lipophilic drugs, the impact of logP on human volume of distribution at steady-state (VDss) predictions, including intermediate fut and Kp values, from six methods: Oie-Tozer, Rodgers-Rowland (tissue-specific Kp and only muscle Kp), GastroPlus, Korzekwa-Nagar, and TCM-New. Method: A sensitivity analysis with focus on logP was conducted by keeping pKa and fup constant for each of four drugs, while varying logP. VDss was also calculated for the specific literature logP values. Error prediction analysis was conducted by analyzing prediction errors by source of logP values, drug, and overall values. Results: The Rodgers-Rowland methods were highly sensitive to logP values, followed by GastroPlus and Korzekwa-Nagar. The Oie-Tozer and TCM-New methods were only modestly sensitive to logP. Hence, the relative performance of these methods depended upon the source of logP value. As logP values increased, TCM-New and Oie-Tozer were the most accurate methods. TCM-New was the only method that was accurate regardless of logP value source. Oie-Tozer provided accurate predictions for griseofulvin, posaconazole, and isavuconazole; GastroPlus for itraconazole and isavuconazole; Korzekwa-Nagar for posaconazole; and TCM-New for griseofulvin, posaconazole, and isavuconazole. Both Rodgers-Rowland methods provided inaccurate predictions due to the overprediction of VDss. Conclusions: TCM-New was the most accurate prediction of human VDss across four drugs and three logP sources, followed by Oie-Tozer. TCM-New showed to be the best method for VDss prediction of highly lipophilic drugs, suggesting BPR as a favorable surrogate for drug partitioning in the tissues, and which avoids the use of fup. [ABSTRACT FROM AUTHOR]

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF. [ABSTRACT FROM AUTHOR]

Microbial secondary infections are violent that cause different varieties of microorganisms. The broad-spectrum antimicrobial agents are the key solution for such infections which can be killed: Gram-positive and Gram-negative bacteria and sometimes supported with antifungal activity as well. Biopolymer-based nanocomposites are globally enhancing the efficiency of loaded materials, especially drugs. Currently, a new formulation of nanocomposite (NCO) based on casein (CN) and hydroxypropyl methylcellulose (HPMC) was used as capping and stabilizing agents for in situ synthesis of silver nanoparticles (AgNPs) and was incorporated with griseofulvin (Gf), an antifungal drug. The prepared NCO was investigated using several techniques such as physiochemical analysis; UV–visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Additionally, the topography and the size were investigated using a scanning electron microscope (SEM) and transmission electron microscope (TEM), which emphasized the successfully prepared NCO with particle size around 80 nm and the size of AgNPs around 30 nm. The dynamic light scattering (DLS) results affirmed these findings where the particle size distribution was recorded at two peaks at 30 and 80 nm as well as average zeta potential was recorded as − 54.2 mV. The prepared NCO was subjected to a release study that reflected a sustained controlled release of Gf for 48 h at different pHs, 1.5 and 7.2, and at pH 8 for 2 h. The NCO exhibited excellent cytocompatibility as well as synergetic antimicrobial activity against Gram-positive and Gram-negative bacteria as well as unicellular and filamentous fungi with MIC50 about 27 µg/mL. Moreover, the time required for the killing was calculated for bacteria and unicellular and filamentous fungi as 16, 18, and 72 h, respectively. Based on that promising data, the prepared NCO was formulated in a green eco-friendly method aboard antimicrobial activity. [ABSTRACT FROM AUTHOR]

The processes of structural relaxation, crystal growth, and thermal decomposition were studied for amorphous griseofulvin (GSF) by means of thermo-analytical, microscopic, spectroscopic, and diffraction techniques. The activation energy of ~395 kJ·mol−1 can be attributed to the structural relaxation motions described in terms of the Tool–Narayanaswamy–Moynihan model. Whereas the bulk amorphous GSF is very stable, the presence of mechanical defects and micro-cracks results in partial crystallization initiated by the transition from the glassy to the under-cooled liquid state (at ~80 °C). A key aspect of this crystal growth mode is the presence of a sufficiently nucleated vicinity of the disrupted amorphous phase; the crystal growth itself is a rate-determining step. The main macroscopic (calorimetrically observed) crystallization process occurs in amorphous GSF at 115–135 °C. In both cases, the common polymorph I is dominantly formed. Whereas the macroscopic crystallization of coarse GSF powder exhibits similar activation energy (~235 kJ·mol−1) as that of microscopically observed growth in bulk material, the activation energy of the fine GSF powder macroscopic crystallization gradually changes (as temperature and/or heating rate increase) from the activation energy of microscopic surface growth (~105 kJ·mol−1) to that observed for the growth in bulk GSF. The macroscopic crystal growth kinetics can be accurately described in terms of the complex mechanism, utilizing two independent autocatalytic Šesták–Berggren processes. Thermal decomposition of GSF proceeds identically in N2 and in air atmospheres with the activation energy of ~105 kJ·mol−1. The coincidence of the GSF melting temperature and the onset of decomposition (both at 200 °C) indicates that evaporation may initiate or compete with the decomposition process. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum ( 13.8% i n 4 9 s amples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development. [ABSTRACT FROM AUTHOR]

Melt viscosity is an essential property in pharmaceutical processes such as mixing, extrusion, fused deposition modeling, and melt coating. Measuring and modeling of the melt viscosity for drug/polymer mixtures is essential for optimization of the manufacturing process. In this work, the melt viscosity of nine formulations containing the drug substances acetaminophen, itraconazole, and griseofulvin, as well as the pharmaceutical polymers Eudragit EPO, Soluplus, and Plasdone S-630, were analyzed with a rotational and oscillatory rheometer. The shear rate, temperature, and drug fraction were varied systematically to investigate their influence on viscosity. The results for the pure polymers showed typical shear-thinning behavior and are fundamental for modeling with the Carreau and Arrhenius approaches. The investigations of the viscosity of the drug/polymer mixtures resulted in a plasticizing or a filler effect, depending on the type of drug and the phase behavior. A drug shift factor was proposed to model the change in viscosity as a function of the drug fraction. On this basis, a universal model to describe the melt viscosity of drug/polymer mixtures was developed, considering shear rate, temperature, and drug fraction. [ABSTRACT FROM AUTHOR]

Griseofulvin (GRFV1) is used in the treatment of many fungal infections, including ringworm and athlete’s foot, as well as fungal infections of the scalp, fingernails, and toenails. However, its bioavailability is limited by poor water solubility. This work was aimed at improving the aqueous solubility of the drug via Polysorbate 80 - modulated nanocrystallization. Two types of nanocrystals (GRFV3 and GRFV2) were generated, respectively, with and without the inclusion of Polysorbate 80 in the nanocrystallization process. The three forms of the drug were subjected to a flowability test, differential scanning calorimetry, Fourier transform infrared spectroscopy, particle size analysis, and aqueous solubility determination. The flowability of the particles was in the order GRFV3 > GRFV2 > GRFV1. The thermogram of the drug powder showed a sharp endothermic transition with a peak at 75 ºC; that of the nanocrystals GRFV2 showed a single sharp endothermic transition with a peak at 170 ºC, while that of GRFV3 showed two endotherms with peaks at 75 ºC and 164 ºC. The nanocrystallization with or without a surfactant did not result in any observable change in the chemical integrity of the drug. The mean particle size was in the order GRFV3 < GRFV2 < GRFV1. There was a significant difference (P < 0.0001) in the aqueous solubility of the three forms of the drug, with GRFV3 having the highest value. Polysorbate 80 - modulated nanocrystallization can increase the aqueous solubility of griseofulvin by 4.14 folds; it is a potential way of improving the bioavailability of the drug.

Tinea capitis is a dermatophyte scalp infection with a marked prevalence among the pediatric population. However, in the last few years, its epidemiology has changed due to increasing population migration worldwide. Host-specific and environmental factors contribute to the pathogenesis of tinea capitis. Clinically, tinea capitis may present as a subtle hair loss accompanied by scalp scaling, alopecia with scaly patches, or alopecia with black dots. A more severe form of tinea capitis is represented by kerion celsi, which clinically presents as a tender plaque covered by pustules and crusts. If left untreated, this dermatophytic infection may resolve with permanent scarring and alopecia. The pathological changes found in tinea capitis are reflected by a spectrum of clinical changes. Zoophilic infections typically prompt an extensive inflammatory reaction, while anthropophilic dermatophytoses often lack inflammation and result in more persistent lesions. Tinea capitis typically requires systemic antifungal therapy. Griseofulvin, terbinafine, itraconazole, and fluconazole are the main antifungal agents used. Currently, the duration of antifungal therapy varies based on the clinical presentation and type of dermatophyte involved. Through the reported cases and literature review, we aim to emphasize the importance of the early recognition of atypical variants of tinea capitis in immunocompetent children for the prompt initiation of systemic antifungal therapy, minimizing the need for prolonged treatment. Additionally, we emphasize the importance of regular laboratory testing during systemic antifungal therapy, particularly liver enzyme tests, to prevent adverse events, especially in cases requiring long-term treatment. [ABSTRACT FROM AUTHOR]

Particle size reduction of poorly water-soluble drug crystals down to the submicron region (0.1–1 µm) is a focus strategy to increase bioavailability. In this context, solid crystalline suspensions (SCS) manufactured in an adapted wet milling process have been introduced as a promising formulation technique. However, for such particle size, agglomeration due to the prevailing attractive interactions poses a major limitation to product quality. As a countermeasure, steric and electrostatic stabilizers have been extensively used in conventional wet grinding applications to introduce kinetic stability to primary particles. In this study the formulation of SCS, containing Xylitol and Griseofulvin, is optimized using the surfactant sodium dodecyl sulfate (SDS). The stabilizer did not impact suspension stability during grinding, as a constant apparent grinding limit (d50=0.35-0.40 µm) was observed over a wide range of concentrations. Nevertheless, redispersion of primary particles from the solidified SCS in water was enhanced at concentrations of 1 wt.% and above. This behavior of the optimized formulation positively impacted the dissolution kinetics of the Griseofulvin particles compared to the binary system. Different imaging techniques revealed the morphology of the solidified Xylitol matrix and the particle location inside it. At 1 wt.% SDS a porous matrix was obtained, which is caused by a foaming process during grinding. Further investigations indicated the importance of this foam regarding the improved particle redispersion, rather than an electrostatic stabilization. A mechanism, which is inspired by particle stabilized foams and emulsions, is proposed. [ABSTRACT FROM AUTHOR]

In response to the urgent demand for innovative antibiotics, theoretical investigations have been employed to design novel analogs. Because griseofulvin is a potential antibacterial agent, we have designed novel derivatives of griseofulvin to enhance its antibacterial efficacy and to evaluate their interactions with bacterial targets using in silico analysis. The results of this study reveal that the newly designed derivatives displayed the most robust binding affinities towards PBP2, tyrosine phosphatase, and FtsZ proteins. Additionally, molecular dynamics (MD) simulations underscored the notable stability of these derivatives when engaged with the FtsZ protein, as evidenced by root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and solvent-accessible surface area (SASA). Importantly, this observation aligns with expectations, considering that griseofulvin primarily targets microtubules in eukaryotic cells, and FtsZ functions as the prokaryotic counterpart to microtubules. These findings collectively suggest the promising potential of griseofulvin and its designed derivatives as effective antibacterial agents, particularly concerning their interaction with the FtsZ protein. This research contributes to the ongoing exploration of novel antibiotics and may serve as a foundation for future drug development efforts. [ABSTRACT FROM AUTHOR]

Pigmented purpuric dermatosis (PPD) comprises a group of skin conditions characterized by flat, nonpalpable petechiae and purpura as a result of capillaritis. Although the precise cause of PPD is as yet unknown, increased vascular permeability and capillary fragility are key factors in its pathophysiology. PPD has diverse clinical presentations, but the histopathology of all these variants essentially remains the same. The initial purpuric lesions develop a golden-brown hue owing to hemosiderin absorption and eventually progress to chronic pigmentary changes. These lesions, which often affect the lower limbs, are either asymptomatic or accompanied by moderate pruritus, and can be difficult to diagnose and treat. There are several subtypes of clinical presentations that have been documented over the years. In order to accurately diagnose PPD, a thorough clinical evaluation and, occasionally, a biopsy may be required. It is essential to identify the condition and reassure patients of its benign nature. Treatment is usually necessary due to the chronic nature of the condition, its consequences on physical and mental well-being, and the presence of significant lesions or itching. In this review, we outline the various prevalent PPDs and discuss their etiopathogenesis, clinical features, and diagnostic and treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. Objective: This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. Patients/Methods: We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. Results: Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. Conclusion: The over‐crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine. [ABSTRACT FROM AUTHOR]

The marine-derived fungal strains KMM 4718 and KMM 4747 isolated from sea urchin Scaphechinus mirabilis as a natural fungal complex were identified as Penicillium sajarovii and Aspergillus protuberus based on Internal Transcribed Spacer (ITS), partial β-tubulin (BenA), and calmodulin (CaM) molecular markers as well as an ribosomal polymerase two, subunit two (RPB2) region for KMM 4747. From the ethyl acetate extract of the co-culture, two new polyketides, sajaroketides A (1) and B (2), together with (2′S)-7-hydroxy-2-(2′-hydroxypropyl)-5-methylchromone (3), altechromone A (4), norlichexanthone (5), griseoxanthone C (6), 1,3,5,6-tetrahydroxy-8-methylxanthone (7), griseofulvin (8), 6-O-desmethylgriseofulvin (9), dechlorogriseofulvin (10), and 5,6-dihydro-4-methyl-2H-pyran-2-one (11) were identified. The structures of the compounds were elucidated using spectroscopic analyses. The absolute configurations of the chiral centers of sajaroketides A and B were determined using time-dependent density functional theory (TDDFT)-based calculations of the Electronic Circular Dichroism (ECD) spectra. The inhibitory effects of these compounds on urease activity and the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans were observed. Sajaroketide A, altechromone A, and griseofulvin showed significant cardioprotective effects in an in vitro model of S. aureus-induced infectious myocarditis. [ABSTRACT FROM AUTHOR]

This article, titled "Griseofulvin in Children: Revisiting the Vintage Drug," discusses the use of griseofulvin as an antifungal treatment for dermatophytosis in children. Griseofulvin was first discovered in 1939 and approved by the FDA in 1959. It is available in tablet or oral suspension form and works by inhibiting mitosis in fungal cells. The article provides dosing regimens for different dermatophyte infections and mentions the efficacy and safety of griseofulvin in children. It also discusses potential adverse effects and drug interactions. Overall, griseofulvin is considered a cost-effective and safe treatment option for dermatophytosis in children. [Extracted from the article]

This study aimed to evaluate the current management of tinea capitis in the United States, specifically focusing on patients aged 0–2 months, 2 months to 2 years, and 2 years to 18 years. An online survey, distributed through the Pediatric Dermatology Research Alliance and the Society of Pediatric Dermatology, revealed the following preferences: fluconazole for those under 2 months, griseofulvin for those aged 2 months to 2 years, and terbinafine for those aged 2 years and older. There exists inter‐provider variation in tinea capitis treatment regimens within the pediatric dermatology community. [ABSTRACT FROM AUTHOR]

Since griseofulvin was marketed as a non-polyene antifungal antibiotic drug in 1958, its poor water solubility has been an issue for its wide applications, and over the last sixty years, many attempts have been made to increase its water solubility; however, a significant result has yet to be achieved. Through supercritical carbon dioxide-assisted cyclodextrin complexation with the addition of a trace amount of water-soluble polymer surfactant, the griseofulvin inclusion complex with HP-γ-cyclodextrin was prepared and confirmed. The 1:2 ratio of griseofulvin and HP-γ-cyclodextrin in the complex was determined based on its NMR study. After complexation with HP-γ-cyclodextrin, griseofulvin's water solubility was increased 477 times compared with that of griseofulvin alone, which is the best result thus far. The complex showed 90% of griseofulvin release in vitro in 10 min, in an in vivo dog pharmacokinetic study; the Cmax was increased from 0.52 µg/mL to 0.72 µg/mL, AUC0–12 was increased from 1.55 μg·h/mL to 2.75 μg·h/mL, the clearance was changed from 51.78 L/kg/h to 24.16 L/kg/h, and the half-life time was changed from 0.81 h to 1.56 h, indicating the obtained griseofulvin complex can be a more effective drug than griseofulvin alone. [ABSTRACT FROM AUTHOR]

Background: 5, 5-diphenylimidazolidine is a heterocyclic hydrocarbon having unique basic structural characteristics in their molecular structure. In this research; we synthesis various 11 derivatives of -[3-(2-hydroxyphenyl)-3-oxopropanoyl]-5,5-diphenylimidazolidine -2,4-dione with anti-fungal activity. The agar well diffusion method was used to conduct the pharmacological screening for antifungal activity. Materials and Methods: All 5, 5-diphenylimidazolidine derivatives were synthesized by conventional method. Benzoin; Benzil; Urea; Glacial Acetic Acid; 4-hydroxyl benzoic acid; Con. HNO3; Formic Acid; 2-Nitro Aniline are used for the synthesis. The structure confirmations were done by FTIR, NMR spectroscopy and MS. Results: In this research; we concluded that; many derivatives give potent anti-fungal activity against fungi. The compound 1-[3-(oxo (phenyl amino)acetic acid)-3-oxopropanoyl]-5,5-diphenylimidazolidine-2,4-dione (BJ); 1-[3-(N-phenylformamide)-3-oxopropanoyl]-5,5-diphenylimidazolidine-2,4-dione (BG); 1-[3-(NPhenyl-2-nitroaniline)-3-oxopropanoyl]-5,5-diphenylimidazolidine-2,4-dione (BE); shown better antifungal activity against Candida albicans. BJ was shown to be the most effective chemical when compared to Griseofulvin and other common medications because it demonstrated greater antifungal action against Aspergillus niger. Conclusion: The anti-fungal activity of the title compounds and their derivatives was studied. Studies on the link between structure and activity revealed that compounds containing 5, 5-dimethylimidazolidinone derivatives with an electron-withdrawing group have higher activity than those containing an electron-donating group. 1-[3-(N-Phenyl-2-nitroaniline)-3-oxopropanoyl]-5,5-diphenylimidazolidine-2,4-dione (BE); 1-[3-(oxo(phenyl-amino) acetic acid)-3-oxopropanoyl]-5,5-diphenylimidazolidine-2,4-dione (BK) shown better antifungal activity against Candida albicans. [ABSTRACT FROM AUTHOR]

The impacts of bead sizes and bead mixtures on breakage kinetics, the number of milling cycles applied to prevent overheating, and power consumption during the nanomilling of drug (griseofulvin) suspensions were investigated from both an experimental and theoretical perspective. Narrowly sized zirconia beads with nominal sizes of 100, 200, and 400 µm and their half-and-half binary mixtures were used at 3000 and 4000 rpm with two bead loadings of 0.35 and 0.50. Particle size evolution was measured during the 3 h milling experiments using laser diffraction. An nth-order breakage model was fitted to the experimental median particle size evolution, and various microhydrodynamic parameters were calculated. In general, the beads and their mixtures with smaller median sizes achieved faster breakage. While the microhydrodynamic model explained the impacts of process parameters, it was limited in describing bead mixtures. For additional test runs performed, the kinetics model augmented with a decision tree model using process parameters outperformed that augmented with an elastic-net regression model using the microhydrodynamic parameters. The evaluation of the process merit scores suggests that the use of bead mixtures did not lead to notable process improvement; 100 µm beads generally outperformed bead mixtures and coarser beads in terms of fast breakage, low power consumption and heat generation, and low intermittent milling cycles. [ABSTRACT FROM AUTHOR]

The emergence and spread of Trichophyton indotineae (T. indotineae) has led to a sea change in the prescription practices of clinicians regarding the management of dermatophytic skin infections. An infection easily managed with a few weeks of antifungals, tinea corporis or cruris, is now often chronic and recurrent and requires prolonged treatment. Rising resistance to terbinafine, with documented squalene epoxidase (SQLE) gene mutations, and slow clinical response to itraconazole leave clinicians with limited treatment choices. However, in these testing times, it is essential that the tenets of antifungal stewardship be followed in making therapeutic decisions, and that the existing armamentarium of antifungals be used in rationale ways to counter this extremely common cutaneous infection, while keeping the growing drug resistance among dermatophytes in check. This review provides updated evidence on the use of various systemic antifungals for dermatophytic infection of the glabrous skin, especially with respect to the emerging T. indotineae species, which is gradually becoming a worldwide concern. [ABSTRACT FROM AUTHOR]

Dermatophytosis is a contagious skin disease affecting domestic and wild animals with considerable zoonotic significance. The disease is caused by fungi known as dermatophytes in the genera Trichophyton, Microsporum and Epidermophyton. A goat was observed with circumscribed alopecic, highly inflammatory, thickly crusted skin lesions on the head region, especially around the eyes. Skin scraping, including hair pullouts, was aseptically obtained and processed for direct examination, isolation and microscopic identification of etiologic agent and supplemented with urease test. The isolate was tested for its susceptibility to fluconazole, griseofulvin, itraconazol and ketoconazole. Direct examination revealed hyaline, septate hyphae in skin scales and chains of endothrix spores within hair shafts, suggesting Trichophyton infection. Colonies on Sabouraud's dextrose agar were white, flat and granular. Microscopic examination of the isolate revealed many oval micro-conidia arranged in grapelike clusters with multi-septate, club-shaped, thin, and smooth-walled macroconidia typical of Trichophyton mentagrophytes. The isolate was urease-positive and sensitive to itraconazole and ketoconazole but resistant to fluconazole and griseofulvin. It was concluded that T. mentagrophytes was the cause of the severe skin lesions in the goat. The need to perform antifungal susceptibility testing on dermatophytes isolated from clinical specimens for effective management of dermatophytosis was emphasized. [ABSTRACT FROM AUTHOR]

The article discusses the rare occurrence of tinea capitis of the eyebrows, primarily caused by Microsporum canis. Trichoscopy is highlighted as a noninvasive tool that aids in diagnosing this condition. The study describes trichoscopic findings in four pediatric patients with tinea capitis of the eyebrows, emphasizing the importance of accurate diagnosis and treatment. The authors stress the significance of trichoscopy in differentiating tinea capitis from other dermatological conditions and recommend mycological culture as the gold standard for diagnosis. [Extracted from the article]

There are several classes/types of drugs that interact with hormonal contraception, which can increase or reduce the effectiveness of the contraception. Contraceptive hormones can also increase or decrease the safety and effectiveness of certain drugs the individual is taking. Therefore, it is important for any health professional who provides contraception to take a through drug history and check interactions before prescribing. Health professionals must ensure contraceptive consultations are thorough, and that these drug interactions are avoided to ensure optimum prescribing and unintended pregnancy. The Faculty of Sexual and Reproductive Health has updated its guidance on drug interactions with hormonal contraception, and this article provides a summary of this updated guidance, along with best practice points. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) to currently available drugs is a major source of worry for researchers. Antibiotic treatment is insufficient and ineffective against many bacteria and fungi as a result of antimicrobial resistance. Novel antimicrobial drugs that can successfully combat microbial resistance are urgently needed. In order to assess their antimicrobial activity, furan-based thiazolidinone and pyrimidine scaffolds (8a–o) have been developed and synthesized. IR, 1 H and 13C NMR, and mass spectrometry have been used to characterize the structures of the newly synthesized analogues (8a–o). The synthesized compounds have been tested for their antimicrobial properties against diverse bacterial and fungal strains. At MIC 12.5 μg/mL, compound 8k shows efficacy against E. coli. Compounds 8d and 8e demonstrate antifungal activity against A. niger at 100 μg/mL. Chloramphenicol, ciprofloxacin and griseofulvin have been employed as reference drugs. [ABSTRACT FROM AUTHOR]

Active pharmaceutical ingredients that have low aqueous solubility pose a challenge in the field of drug delivery. In this paper we report for the first time the synthesis of nano-structured, hydrophilized polylactic acid (nf PLA) and its application in the delivery of low solubility drugs. Microwave induced acid oxidation was used to generate nf PLA where the oxygen concentration increased from 27.0 percent to 41.0 percent. Also, the original non dispersible PLA was converted to a relatively dispersible form with an average particle size of 131.4 nm and a zeta potential of -23.3 mV. Small quantities of the nf PLA were incorporated into the crystals (0.5 to 2.0 % by weight) of a highly hydrophobic, low solubility antifungal drug Griseofulvin (GF) to form a composite (GF- nf PLA). An antisolvent approach was used for the synthesis of the drug composite. SEM and Raman imaging showed non-uniform distribution of the nf PLA on the crystal surface. The solubility of GF increased from 8.89 µg/mL to as high as 49.67 µg/mL for the GF- nf PLA. At the same time zeta potential changed from -15.4 mV to -39.0 mV, therefore the latter was a relatively stable colloid. Octanol-water partitioning also showed a similar effect as logP reduced from 2.16 for pure GF to 0.55 for GF- nf PLA. In vitro dissolution testing showed six times higher aqueous solubility of GF- nf PLA compared to pure GF. The time for 50 (T 50) and 80 % (T 80) dissolution reduced significantly for the nf PLA composites; T 50 reduced from 40.0 to 14.0 min and T 80 reduced form unachievable to 47.0 min. Overall, the PLA which is an FDA approved, bioabsorbable polymer can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower the required dosage for drugs. [Display omitted] • Microwave radiation triggered for hydrophilic functionalization of PLA. • Nano functionalized polymer was effectively surface dispersed into griseofulvin. • nf PLA integration had no alternating effect on crystal surface and structure morphology. • Composite drug produced upto 6.0 times increase in aqueous solubility. • Cold antisolvent precipitation technology developed formulated drugs release rates. [ABSTRACT FROM AUTHOR]

The solubility of griseofulvin in buffer solutions (pH 2.0 and 7.4), 1-octanol and hexane was measured in the temperature range 293.15–313.15 K by the shake flask method. It was found that griseofulvin is poorly soluble in aqueous buffer solutions (x≤8.63·10−7), while the best solubility is observed in 1-octanol (x≤6.56·10−4). The solubility evaluation in different solvents with the help of Hansen solubility parameters showed the consistency with the experimental data. The solubility was revealed to significantly depend on the dispersion interactions and polar bonds. The dissolution and solvation thermodynamic functions of the drug were calculated. The Gibbs energy and enthalpy of drug dissolution in aqueous and organic solvents are positive, which characterizes the dissolution process as hindered and endothermic. The van't Hoff and Apelblat equations gave good correlations when used for modeling the experimental solubility results. Based on the data on the solubility and thermophysical parameters of the compound, the temperature dependences of the activity coefficients were determined and the excess thermodynamic functions of dissolution were calculated. Positive deviation from ideality was observed in all the solvent-solute systems studied. The partition coefficients of the drug in the 1-octanol/buffer pH 7.4 system were obtained and the transfer thermodynamic functions were derived. It was established that the drug distribution from the aqueous solution to the octanol phase was thermodynamically favorable and endothermic. [ABSTRACT FROM AUTHOR]

Low water solubility and high permeability present formulation challenges for drugs categorized as Biopharmaceutics Classification System (BCS) Class II, resulting in reduced bioavailability. This research focuses on addressing the solubility issues of BCS Class II drugs, including Simvastatin, Ketoprofen, griseofulvin, ibuprofen, ketoconazole, and carbamazepine, which exhibit high permeability but poor solubility. A potential strategy to improve the solubility and bioavailability of these drugs is the utilization of nanosuspensions. This study investigates the application of nanosuspension technology to enhance the solubility of Ketoprofen, a BCS Class II drug. By reducing the drug's particle size within the nanosuspension, solubility is improved, leading to increased bioavailability and optimized therapeutic efficacy. The research includes in vitro and in vivo experiments to evaluate the drug release profiles and bioavailability of Ketoprofen-loaded nanosuspensions. Significant findings from this research include the demonstration of improved bioavailability and enhanced drug release properties achieved with the nanosuspension formulation. In vitro studies show increased drug dissolution rates and improved release profiles compared to conventional formulations. In vivo experiments reveal enhanced pharmacokinetic parameters and therapeutic effectiveness of Ketoprofen when administered through the nanosuspension. These results highlight the potential of nanosuspensions as an efficient drug delivery system for BCS Class II drugs, addressing their solubility limitations and improving their bioavailability. The findings contribute to the development of novel strategies in pharmacology for enhancing drug solubility and therapeutic outcomes. Overall, this research emphasizes the significance of nanosuspension technology in optimizing the delivery of BCS Class II drugs and offers valuable insights for future formulation development and therapeutic applications. [ABSTRACT FROM AUTHOR]

The emergence and spread of Trichophyton indotineae (T. indotineae) has led to a sea change in the prescription practices of clinicians regarding the management of dermatophytic skin infections. An infection easily managed with a few weeks of antifungals, tinea corporis or cruris, is now often chronic and recurrent and requires prolonged treatment. Rising resistance to terbinafine, with documented squalene epoxidase (SQLE) gene mutations, and slow clinical response to itraconazole leave clinicians with limited treatment choices. However, in these testing times, it is essential that the tenets of antifungal stewardship be followed in making therapeutic decisions, and that the existing armamentarium of antifungals be used in rationale ways to counter this extremely common cutaneous infection, while keeping the growing drug resistance among dermatophytes in check. This review provides updated evidence on the use of various systemic antifungals for dermatophytic infection of the glabrous skin, especially with respect to the emerging T. indotineae species, which is gradually becoming a worldwide concern.

Objective Dermatophytoses, one of the most ancient diseases, is becoming a menace in recent times. This has made the knowledge of antifungal susceptibility a priority in today's times. Material and Methods This is a prospective study conducted over 18 months including all dermatophytes isolated during the period. Dermatophytes were identified by routine phenotypic methods. Antifungal susceptibility testing was performed for griseofulvin, terbinafine, and itraconazole as per the Clinical Laboratory Standard Institute M38 A2, and minimum inhibitory concentrations (MICs) were read after 5 days. Results Patient details and associated risk factors were recorded. Fixed dose combinations with steroids were associated with 79.3% (46 out of 58) of patients with dermatophytosis of skin. Among the 72 dermatophytes isolated during the study period, 58 (80.5%) were isolated from skin scrapings and 14 (19.4%) from nail samples. Tinea corporis with cruris was the most common presentation. The most common dermatophyte isolated from skin scrapings was Trichophyton mentagrophytes complex (70.6%, 41 out of 58), while from nail samples it was Trichophyton rubrum complex (78.57%, 11 out of 14). Based on the MIC50 and MIC90 results, itraconazole showed the lowest MICs, followed by terbinafine and then griseofulvin. Conclusion With the changing epidemiology of species distribution and antifungal resistance, there is a need for continuous surveillance of these parameters of dermatophytes.

Background. Microsporia is a zooanthroponotic mycosis of skin and hair caused by fungi genus Microsporum. Microsporia is most common among children, including infants. The microsporia incidence has slow steady increase over recent years.Clinical cases description. Follow-up results of two children of different ages (younger/older than 1 year) with microsporia are presented. Successful management approach is shown. Major limitations of drug therapy in infants as well as common therapeutic errors were analyzed.Conclusion. Diagnosis and management of microsporia in infants and young children is a challenging task. Major errors in microsporia management in patients of these age groups are associated with peculiarities of clinical picture as well as limited variations of drugs that are appropriate for the requirements on efficacy and safety of therapy among young children.

Griseofulvin was considered an effective agent for cancer therapy in past decades. Although the negative effects of griseofulvin on microtubule stability are known, the exact target and mechanism of action in plants remain unclear. Here, we used trifluralin, a well-known herbicide targeting microtubules, as a reference and revealed the differences in root tip morphology, reactive oxygen species production (ROS), microtubule dynamics, and transcriptome analysis between Arabidopsis treated with griseofulvin and trifluralin to elucidate the mechanism of root growth inhibition by griseofulvin. Like trifluralin, griseofulvin inhibited root growth and caused significant swelling of the root tip due to cell death induced by ROS. However, the presence of griseofulvin and trifluralin caused cell swelling in the transition zone (TZ) and meristematic zone (MZ) of root tips, respectively. Further observations revealed that griseofulvin first destroyed cortical microtubules in the cells of the TZ and early elongation zone (EZ) and then gradually affected the cells of other zones. The first target of trifluralin is the microtubules in the root MZ cells. Transcriptome analysis showed that griseofulvin mainly affected the expression of microtubule-associated protein (MAP) genes rather than tubulin genes, whereas trifluralin significantly suppressed the expression of αβ-tubulin genes. Finally, it was proposed that griseofulvin could first reduce the expression of MAP genes, meanwhile increasing the expression of auxin and ethylene-related genes to disrupt microtubule alignment in root tip TZ and early EZ cells, induce dramatic ROS production, and cause severe cell death, eventually leading to cell swelling in the corresponding zones and inhibition of root growth. [ABSTRACT FROM AUTHOR]

Scientists have been faced with the challenge of selecting the right solubilizing excipients for solubility enhancement of poorly water-soluble active pharmaceutical ingredients for decades. In this investigation, the purpose was to ease some of those challenges by developing a first-intent matrix for selecting solubilizing excipients that may potentially be used in an oral solid dosage formulation. This was accomplished by generating 2304 data points using high throughput experimentation to assess the impact of eleven commonly used formulation excipients, at varying levels, on the solubility enhancement of a weak acid (Ibuprofen), weak base (Cinnarizine), and non-ionizable (Griseofulvin) drug substance over a time span from 1 h to equilibrium in simulated gastrointestinal fluids (SGF, FaSSIF, FeSSIF) and water. The results indicate that the enhancement of drug concentrations by use of solubilizing excipients (surfactants and stabilizers) in oral solid dosage forms depends on the type, the amount of excipient, and the pH of the media. The importance of this work is that formulation scientists now have a new addition to the formulation development toolkit for selecting the right solubilizing excipients and amounts suitable for solubility enhancement based on the class of active pharmaceutical ingredients. This first-intent solubilizer selection approach for the different drug classes simplifies the early development process to enable acceleration to candidate selection, formulation design, and product development for first-time-in-human studies. [Display omitted] • Solubility of pharmaceutical compounds can be enhanced by the use of excipients. • HTE can build large data which produces accurate predictive models. • Statistical analysis of data gives insight to significant experimental factors. • Solubility in simulated body fluids provides accurate representation of in-situ. [ABSTRACT FROM AUTHOR]