Formulation Of Itraconazole Research Articles

FATAL ACUTE HEMOLYSIS FOLLOWING TRIAZOLE THERAPY IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS).

Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins (Spheniscus demersus) from four institutions. All penguins underwent stressful events (e.g. relocation, induced molt) and were administered commercial liquid itraconazole formulations or compounded voriconazole liquid suspension. Observed clinical signs in affected penguins prior to death included hyporexia, weight loss, lethargy, dyspnea, red-tinged droppings, and obtunded mentation. Intra- and extravascular hemolysis and hemoglobinuric nephrosis were the primary pathologic manifestations on postmortem examination. The concentration-dependent hemolytic potentials of itraconazole, voriconazole, and commercial and compounded vehicle suspensions were evaluated in vitro by exposing chicken whole blood as a surrogate for penguin blood. Hemoglobin content in blood plasma was then measured by spectrophotometry. Neither itraconazole nor voriconazole alone induced hemolysis in vitro. The vehicle ingredients sorbitol and hydromellose induced hemolysis, but not at predicted plasma levels in chicken erythrocytes, suggesting neither the azole antifungals nor their major vehicles alone were likely to contribute to hemolysis in vivo in these penguins. Potential mechanisms of toxicosis include generation of an unmeasured reactive metabolite causing hemolysis, preexisting erythrocyte fragility, or species-specific differences in hemolytic thresholds that were not assessed in the chicken erythrocyte model. More research is needed on the potential for toxicosis of azole antifungal drugs and carrier molecules in this and other avian species.

Pharmaceutical Compounding in Veterinary Medicine: Suspension of Itraconazole.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.

Modification of physicochemical properties of chitosan to improve its pharmaceutical and agrochemical potential applications

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics.The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies.The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination.Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan.This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.

IADVL SIG Recalcitrant Dermatophytosis Position Statement on Super Bioavailable Itraconazole.

Itraconazole (ITZ) has been the mainstay of oral antifungal treatment for the current epidemic of recalcitrant dermatophytosis (RD) in India. Recently, a newer formulation of ITZ, super bioavailable itraconazole (SUBA-ITZ), is made available in the market by many pharmaceutical companies. It is important for dermatologists to understand the pharmacokinetic properties of SUBA-ITZ vis-a-vis conventional pellet formulation to use it effectively and safely. Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) has established a special interest group for recalcitrant dermatophytosis (SIG-RD) to strengthen research, continuing medical education, and industry collaboration on the subject. This position statement on SUBA-ITZ by SIG-RD is an attempt to address current pieces of evidence and the position of this new formulation in the management of RD.

Efficacy of super bioavailable itraconazole in the management of dermatophytosis in India

Itraconazole (ITZ) is a commonly prescribed oral antifungal agent in India and has a low minimum inhibitory concentration when compared to other oral antifungals. However, clinicians have reported inconsistent clinical responses despite its high skin levels, which may be due to variations in pelletization parameters, which affect its bioavailability and serum levels. Conventional ITZ has a maximum bioavailability of 55%; however, this is unpredictable and inconsistent. In contrast, the novel ITZ formulation, super bioavailable ITZ (ITZ-SB), has targeted drug release in the small intestine, resulting in predictable serum levels with minimal interindividual variability. This makes it a potentially useful drug in treating recalcitrant dermatophytosis. This expert opinion highlights the benefits of novel ITZ-SB with the incorporation of SUBA® technology. The SUBA® technology improves the bioavailability of poorly soluble drugs by ‘solid dispersion’ in polymer to increase drug absorbency. This technology also has potential to reduce variability in absorption and adverse effects. Benefits of this technology include more predictable clinical response and lower drug quantities necessary to achieve therapeutic blood levels, making it a promising treatment option for recalcitrant dermatophytosis. Fixtral SB, which uses this technology, is a novel weapon in the arsenal of treatments for superficial mycoses.

The effects of formulation on the pharmacokinetics of itraconazole and amiodarone in dogs after oral administration of a combination product, commercial products, and compounded products.

This study evaluated four different formulations of itraconazole and amiodarone. Formulation 1 was Vida's combination tablet containing both active pharmaceutical ingredients (APIs). Formulation 2 was separate, commercially available human generic capsules and tablets of itraconazole and amiodarone, respectively. Formulation 3 was separate, compounded suspensions of itraconazole and amiodarone. Formulation 4 was a compounded chewable tablet of itraconazole. Eight female dogs were dosed with 5 mg/kg of itraconazole and 15 mg/kg amiodarone (except for formulation 4, which only received 5 mg/kg itraconazole) once weekly for 4 weeks using a modified Latin Square design, ensuring that all dogs received all formulations with a 7-day washout between treatments. Animals were fasted overnight prior to each dose administration, with food returned to all animals 4 h post-dose. Blood samples (3 mL) were collected pre-treatment (0) and at appropriate time points over 72 h after each dose for a total of 14 samples per dog per treatment. There was high variability in the serum concentration data within treatment groups for itraconazole. The compounded suspensions were difficult to dose due to the nature of the formulations. The volumes dosed were accurate and consistent, but the suspension was thin and settled immediately when shaking was stopped for both itraconazole and amiodarone. All serum samples following itraconazole chewable tablet administration were not detectable or just above itraconazole's LOQ and thus did not allow for pharmacokinetic determination.

A Critical Review on the Dosing and Safety of Antifungals Used in Exotic Avian and Reptile Species.

Antifungals are used in exotic avian and reptile species for the treatment of fungal diseases. Dose extrapolations across species are common due to lack of species-specific pharmacological data. This may not be ideal because interspecies physiological differences may result in subtherapeutic dosing or toxicity. This critical review aims to collate existing pharmacological data to identify antifungals with the most evidence to support their safe and effective use. In the process, significant trends and gaps are also identified and discussed. An extensive search was conducted on PubMed and JSTOR, and relevant data were critically appraised. Itraconazole or voriconazole showed promising results in Japanese quails, racing pigeons and inland bearded dragons for the treatment of aspergillosis and CANV-related infections. Voriconazole neurotoxicity manifested as seizures in multiple penguins, but as lethargy or torticollis in cottonmouths. Itraconazole toxicity was predominantly hepatotoxicity, observed as liver abnormalities in inland bearded dragons and a Parson's chameleon. Differences in formulations of itraconazole affected various absorption parameters. Non-linearities in voriconazole due to saturable metabolism and autoinduction showed opposing effects on clearance, especially in multiple-dosing regimens. These differences in pharmacokinetic parameters across species resulted in varying elimination half-lives. Terbinafine has been used in dermatomycoses, especially in reptiles, due to its keratinophilic nature, and no significant adverse events were observed. The use of fluconazole has declined due to resistance or its narrow spectrum of activity.

Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data

Itraconazole is a potent inhibitor of cytochrome P450 3A4 (CYP3A4), associated with numerous drug-drug interactions (DDI). PUR1900, a dry powder formulation of itraconazole for oral inhalation, results in high lung and low systemic exposure. This project used physiologically based pharmacokinetic (PBPK) modeling to assess the DDI potential of inhaled PUR1900, using midazolam as a “victim drug.” The basic and mechanistic static models evaluated the DDI potential of PUR1900, assuming 5 mg of midazolam coadministration at steady-state itraconazole exposure. Subsequently, Simcyp® PBPK simulation software and pharmacokinetic data from a Phase 1 clinical trial with PUR1900 (NCT03479411) were used to optimize an existing itraconazole PBPK model. The model was applied to investigate the potential for CYP3A4 DDI when 5 mg of midazolam is co-administered with inhaled PUR1900 at a steady state in a virtual healthy population at PUR1900 doses up to 40 mg per day. The basic static and mechanistic static models suggested a strong likelihood for DDI with inhaled PUR1900. The PBPK model was consistent with PUR1900 Phase 1 trial data. The geometric mean Cmax and AUC ratios of midazolam at a maximum dose of 40 mg PUR1900 were 1.14 and 1.26, respectively, indicating a minimal likelihood of DDI with inhaled PUR1900. The low systemic exposure of itraconazole when administered as PUR1900 results in minimal to no CYP3A4 inhibition, reducing the concern of drug-drug interactions. As the risk of CYP3A4 DDI is predicted to be significantly lower when itraconazole is administered via oral inhalation as PUR1900, it is likely that PUR1900 can be safely used for the treatment of pulmonary fungal infections in patients taking pharmaceuticals currently contraindicated with oral itraconazole.Graphical

A multicenter, retrospective study to evaluate the effectiveness, safety, and utilization patterns of super bioavailable itraconazole 50 mg in superficial dermatophytic infections

<p class="abstract"><strong>Background:</strong> Objectives of the study were to assess the clinical characteristics of patients with superficial dermatophytic infections, and to evaluate the safety and effectiveness of super bioavailable (SB) itraconazole 50 mg.</p><p class="abstract"><strong>Methods:</strong> In this cross-sectional observational study, data of patients with superficial dermatophytic infections treated as per physician’s discretion was collected retrospectively from 71 centers across India between April 2021 and March 2022. Patient’s demographics, prescribing patterns of SB-itraconazole, and clinician-rated effectiveness and safety were evaluated.<strong></strong></p><p class="abstract"><strong>Results:</strong> Of 432 analyzed patients, 72.22% (n=312) had new infections, 27.77% (n=120) had recalcitrant/recurrent infections. Majority of the patients were males (66%) and aged 21-40 years (72.45%). <em>Tinea corporis</em> (27.08%) was the most common fungal infection followed by <em>Tinea cruris</em> (20.60%). SB-itraconazole was most commonly prescribed with water (63.88%; n=276); majority (55.8%) of the patients received SB-itraconazole post-meals. Majority of the patients achieved clinical (naïve: 71.47%; recalcitrant: 79.17%) cures within 4 weeks. The efficacy was excellent/good in 71.95% of patients who received SB-itraconazole as the first choice over conventional itraconazole for overall benefits as per the clinician’s global assessment; and in 87.22% of patients who received concomitant acid-lowering drugs. Most (83.33%) patients reported excellent/good compliance with SB-itraconazole. The clinicians’ rated this newer formulation of itraconazole (SB-itraconazole) as excellent/good in efficacy (83.33%) and safety (79.17%) for most patients.</p><p class="abstract"><strong>Conclusions:</strong> SB-itraconazole was effective and safe in patients with superficial dermatophytic infections. The effectiveness of SB-itraconazole was similar with high response rates for naïve and recalcitrant cases. Further, the efficacy was excellent/good in most patients receiving SB-itraconazole as the first choice over conventional itraconazole, or who received concomitant acid-lowering drugs.</p>

Development and characterization of itraconazole non-aqueous creams for the treatment of topical fungal infections

Itraconazole is a broad-spectrum triazole antifungal agent used to prevent and treat fungal infections. Itraconazole is commercially available as an oral and intravenous formulation; however, its administration via these routes is associated with various side effects, such as hepatotoxicity, peripheral neuropathy, cardiac dysrhythmia, and hearing loss. The objective of the current study was to prepare a stable non-aqueous topical cream loaded with itraconazole for prolonged drug contact, improved drug permeation and penetration into skin layers, and to prevent the side effects associated with other routes of administration for improved therapeutic outcomes. The developed creams were characterized for drug content, pH, texture analysis, rheology behavior, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release, ex vivo drug permeation through human cadaver skin, and stability. The lead formulations were stable over three months (the last time-point tested) during refrigeration and room-temperature storage. The cream formulation developed with 15% w/w Transcutol® P improved itraconazole permeation and deposition through the skin by 8.4- and 8.2-fold, compared to the drug solution, respectively. Thus, itraconazole -loaded non-aqueous creams can serve as alternative drug delivery platforms for the treatment of fungal skin infections over oral/parenteral itraconazole formulations.

Comparative real-world effectiveness and safety of super-bioavailable itraconazole 50 mg bd and 65 mg bd in the management of dermatophytosis

<p>In recent times, India has witnessed a steep surge in prescription of itraconazole in the management of dermatophytosis.<sup>1</sup> But due to its pharmacokinetics, it has shown multiple variations in the results. To overcome these challenges, a newer itraconazole formulation i.e. super-bioavailable itraconazole (SBITZ) has been launched recently in India. Currently, there are 4 different strengths of SBITZ which are approved by DCGI.<sup>2,3</sup> But there is no any clinical data regarding comparison of different strength of SBITZ. This retrospective analysis aimed to compare two different strengths of SBITZ; 50 mg and 65 mg in the management of dermatophytosis.</p>

Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.

Asciminib is a first‐in‐class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P‐glycoprotein (P‐gp) and possesses pH‐dependent solubility in aqueous solution. This report summarizes the results of two phase I studies in healthy subjects aimed at assessing the impact of CYP3A and P‐gp inhibitors, CYP3A inducers and acid‐reducing agents (ARAs) on the pharmacokinetics (PK) of asciminib (single dose of 40 mg). Asciminib exposure (area under the curve [AUC]) unexpectedly decreased by ~40% when administered concomitantly with the strong CYP3A inhibitor itraconazole oral solution, whereas maximum plasma concentration (Cmax) decreased by ~50%. However, asciminib exposure was slightly increased in subjects receiving an itraconazole capsule (~3%) or clarithromycin (~35%), another strong CYP3A inhibitor. Macroflux studies showed that cyclodextrin (present in high quantities as excipient [40‐fold excess to itraconazole] in the oral solution formulation of itraconazole) decreased asciminib flux through a lipid membrane by ~80%. The AUC of asciminib was marginally decreased by concomitant administration with the strong CYP3A inducer rifampicin (by ~13–15%) and the strong P‐gp inhibitor quinidine (by ~13–16%). Concomitant administration of the ARA rabeprazole had little or no effect on asciminib AUC, with a 9% decrease in Cmax. The treatments were generally well tolerated. Taking into account the large therapeutic window of asciminib, the observed changes in asciminib PK following multiple doses of P‐gp, CYP3A inhibitors, CYP3A inducers, or ARAs are not considered to be clinically meaningful. Care should be exercised when administering asciminib concomitantly with cyclodextrin‐containing drug formulations.

Application of tiny-TIM as a mechanistic tool to investigate the in vitro performance of different itraconazole formulations under physiologically relevant conditions

The increasing number of poorly water-soluble compounds in drug development is one of the major challenges in oral drug delivery nowadays. For rational formulation development, biopharmaceutical tools are needed that closely simulate the conditions present within the human gastrointestinal (GI) tract in order to early predict the potential effect of important factors like meal intake or acid-reducing agents on oral bioavailability. The tiny-TIM system equipped with the advanced gastric compartment is one of the most realistic in vitro models for the simulation of the physiological processes occurring in human stomach and small intestine. In the present study, this model was applied to study the in vitro performance of an ASD-based formulation of itraconazole under different clinically relevant conditions. Apart from the assessment of the bioaccessible fraction (i.e., the fraction available for drug absorption), the implementation of two additional sampling ports enabled the measurement of intraluminal concentration profiles. Along with solubility experiments in biorelevant media, deeper mechanistic insights into drug product performance in different prandial states as well as in case of gastric pH modification could be generated. The comparison of the in vitro data with published in vivo data revealed that the model successfully predicted the effect of food intake as well as of modified gastric pH conditions on the bioavailability of itraconazole from this formulation. In contrast, the negative food effect observed for an oral solution formulation could not be predicted. For this cyclodextrin-based formulation, the formulation effect on permeation needs to be considered. Nonetheless, the data presented in this study showed that tiny-TIM is an interesting tool to mechanistically study the impact of different physiological conditions on drug release from oral drug products.

Serum and sebum pharmacokinetics evaluation of a novel formulation of itraconazole in healthy volunteers

Serum and sebum pharmacokinetics evaluation of a novel formulation of itraconazole in healthy volunteers

120. An open-label comparative trial of SUBA-itraconazole (SUBA) versus conventional itraconazole (c-itra) for treatment of proven and probable endemic mycoses (MSG-15): a pharmacokinetic (PK) and adverse Event (AE) analysis

BackgroundC-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds.MethodsSubjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis.Results89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time ConclusionCompared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

An Open-Label, Randomized, Double-Arm Clinical Trial to Compare the Effectiveness and Safety of Super Bioavailable Itraconazole Capsules and Itraconazole Capsules in the Management of Dermatophytosis in India.

PurposeA new oral formulation of itraconazole, called super bioavailable itraconazole (SBITZ), has been launched in India, exhibiting greater bioavailability than conventional itraconazole (CITZ). No clinical studies on its effectiveness and safety in dermatophytosis in comparison with CITZ have been conducted in India. Hence, the aim of this clinical study was to compare the effectiveness and safety of SBITZ capsules and CITZ capsules in dermatophytosis.Patients and MethodsThis was an open-label, randomized, double-arm clinical study in which 70 patients (≥18 years of age) of either gender and diagnosed with tinea cruris, tinea corporis, and/or tinea faciei were included. The study was divided into two parts, the first part comprising a treatment period of 4 weeks and the second part an observation period for recurrence, comprised of another 4 weeks, thus making an entire study duration of 8 weeks.ResultsOf the 70 patients enrolled in this study, 59 (33 patients in the CITZ group and 26 patients in the SBITZ group) were included in the final analysis. In both groups, most patients were diagnosed with tinea cruris et corporis, with five or more lesions. At week 4, 11 patients (33.33%) and 17 patients (65.38%) had achieved complete cure (p<0.05), whereas 22 patients (66.67%) and 22 patients (84.61%) had achieved mycological cure (p=0.14), in the CITZ and SBITZ groups, respectively. During the observation period, recurrence was seen in 1/11 and 4/17 completely cured patients in the CITZ and SBITZ groups, respectively (p=0.15). A significant difference was noted in resolution of symptoms as well as lesions of dermatophytosis in the SBITZ group (p<0.05). Both treatments were found to be safe and well tolerated.ConclusionIn the light of real-world evidence on effectiveness and safety, SBITZ should be considered as a potent therapeutic choice to effectively control the current menace of dermatophytosis in India.

Development, characterization and preclinical evaluation of nanosized liposomes of itraconazole for topical application: 32 full factorial design to estimate the relationship between formulation components

The objective of the study was to statistically develop a novel formulation of itraconazole (ITZ) loaded nanosized liposomes (NLPs) for effective topical delivery against superficial fungal infections. Target formulation was prepared by thin-film hydration, and was optimized by employing a two-step design of experiments (DoE) approach, which comprised a fractional factorial design for screening of ‘vital few’ factors, and response surface mapping optimized using a fractional factorial and 32 full factorial design of experiments. Overlay of response maps for percent drug entrapment (PDE), vesicle size, ITZ skin retention and permeation performed to obtain the optimized ITZ loaded NLPs (OPT-NLPs) suspension. The liposome suspension was gelled to improve topical applicability. OPT-NLPs formulation was able to show high PDE (78.69 ± 3.17%), and average vesicle size of 358.2 ± 9.45 nm and mean zeta potential of 20.66 ± 0.74 mV were observed. Additionally, noticeably higher ITZ skin retention (44.39 ± 1.32 μg/cm2) and cumulative 6-h drug permeation (14.81 ± 0.48 μg/cm2) were observed in excised rat skin in comparison to conventional cream and oily solution of ITZ. Also, standardized Tinea pedis animal model was used to evaluate in vivo antifungal efficacy observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to those treated with commercial topical and oral antifungal therapies. Our study suggests that the developed formulation may be a promising and rapid alternative to conventional antifungal therapies against dermatophytosis.

Clinical assessment of Super bioavailable Itraconazole 50 mg in dermatophytosis (Clear 50)

Super bioavailable itraconazole (SBITZ) is a newer formulation of itraconazole which is recently launched in India. But there is no published clinical evidence of SBITZ in the management of dermatophytosis in Indian patients.A Real world retrospective data analysis was conducted with 346 dermatologists across India to assess the response of Indian patients with dermatophytosis who were prescribed super bioavailable itraconazole 50 mg twice a day for 4 weeks.Out of 4625 patients’ data, 2743 were included for final analysis. Mean age of patients was 36.17±12.05 years with male preponderance. Most of the patients were diagnosed as T. cruris. At the end of treatment, 51% of patients achieved complete clinical cure while 46% achieved clinical improvement (&amp;#62;50% symptom clearance) and 3% were labelled as clinical failure. About 70% patients achieved clearance in body surface area. Mean total symptom score (TSS) was reduced to 0.74±1.1 from 7.29±1.73 while mean BSA score was reduced from 1.96±0.83 to 0.38±0.65 (p&amp;#60;0.05). Similar type of improvements were seen in naïve, recurrent and chronic dermatophytosis patients. A total of 61 adverse effects (AE) were reported from 56 patients. All the AEs were mild to moderate in nature and did not require discontinuation of therapy.Patients treated with super bioavailable itraconazole showed greater improvement in clearance of symptoms as well as lesions. Additionally, it showed significant improvement in naïve, recurrent and chronic patients enabling its placement in armamentarium of management of all types of dermatophytosis.

Comparative clinical effectiveness and safety of super bioavailable itraconazole and conventional itraconazole in management of dermatophytosis: a retrospective data analysis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; A newer itraconazole formulation i.e., super bioavailable itraconazole has been launched recently in India which is claimed to overcome all the pharmacokinetic challenges faced with conventional itraconazole. The present retrospective data analysis was undertaken to evaluate the effectiveness and safety of super bioavailable itraconazole in comparison with conventional itraconazole in the treatment of dermatophytosis in Indian patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The present multi-centric, retrospective data analysis was done at 12 dermatological centers across India from July 2020 to December 2020. Medical records of patients of dermatophytosis, who were prescribed with either super bioavailable itraconazole 50 mg twice daily for four weeks or conventional itraconazole 100 mg twice daily for four weeks were included in the study.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 56% patients (n=30) in super bioavailable itraconazole group achieved complete clearance of their symptoms (cured) compared to only 34% patients (n=17) in conventional itraconazole group and this difference was statistically significant (p=0.02). Significantly more patients achieved complete clearance of their lesions in super bioavailable itraconazole-37 patients (69%) compared to conventional itraconazole group-25 patients (49%) at the end of 4 week therapy (p=0.04). The difference in total symptom score (∆TSS) in super bioavailable itraconazole group was more (5.81) as compared to conventional itraconazole group (4.75) (p=0.09). Both the treatment were well tolerated.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; From the findings of the present study, super bioavailable itraconazole was more effective with similar safety profile as compared to conventional itraconazole in the treatment of dermatophytosis.&lt;/p&gt;

Preparation of Topical Itraconazole with Enhanced Skin/Nail Permeability and In Vivo Antifungal Efficacy against Superficial Mycosis.

In this study, a stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was designed to provide effective treatment against superficial mycosis. Herein, ITZ was incorporated into a solution composed of ethanol, benzyl alcohol, hydrochloric acid, Transcutol P, and cyclomethicone as a delivery vehicle, solubilizer, protonating agent, permeation enhancer, and spreading agent, respectively. At 72 h, the optimal topical ITZ formulation (ITZ–TF#11) exhibited 135% enhanced skin permeability, which led to increases in drug deposition in the stratum corneum, epidermis, and dermis of 479%, 739%, and 2024%, respectively, compared with the deposition of 1% ITZ in ethanol (control). Moreover, on day 7, ITZ–TF#11 demonstrated 2.09- and 2.30-fold enhanced nail flux and drug deposition, compared with the control. At a dose of 40 mg/kg/day, ITZ–TF#11 showed 323% greater lesion recovery, a 165% lower mean erythema severity score, and a 37% lower mean logarithm of viable fungal cells in skin in the treated area, compared with mice that received oral ITZ at the same dose. Overall, the findings imply that ITZ–TF#11 is a superior alternative to oral ITZ for treatment of superficial mycosis.