Thyme Oil-Containing Fluconazole-Loaded Transferosomal Bigel for Transdermal Delivery.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 µg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections.

Nanolipid Gel of an Antimycotic Drug for Treating Vulvovaginal Candidiasis-Development and Evaluation.

This paper focuses on the development and evaluation of mucoadhesive vaginal gel of fluconazole using nanolipid carriers to enhance tissue deposition in treating vulvovaginal candidiasis. Treatment of vulvovaginal candidiasis includes antimycotic agents prescribed for 1 to 7 days or longer, in relapse either orally or topically. The delivery of fluconazole as nanolipid carriers in vaginal gel can be proposed as suitable alternative to the existing conventional formulations to improve the patient acceptability, compliance and localized drug action. The nanolipid carriers of fluconazole were prepared by phase inversion temperature technique and incorporated into Carbopol 974P as gelling polymer. GRAS excipients selected and optimized were Precirol ATO 5, oleic acid and Kolliphor RH 40 to produce nanolipid dispersions. Stable nanolipid dispersions were developed using sodium dodecyl sulfate as the charge inducer. The optimized nanolipid dispersion of fluconazole had particle size, polydispersity index and zeta potential value of 158.33 ± 2.55 nm, 0.278 ± 0.003 and - 27.33 ± 0.40 mV, respectively and the average entrapment of fluconazole in the lipid carriers was found to be 67.24 ± 0.87%. The optimized vaginal gel had satisfactory mucoadhesive strength and rheological properties to facilitate vaginal application. The fluconazole release from the gel was sustained showing 30.69 ± 1.02% drug deposition in the porcine vaginal mucosa at the end of 8 h with improved antifungal activity against Candida albicans during well diffusion studies. The optimized gel was non-irritant to the vaginal mucosa of female Wistar rats with no signs of erythema or edema.

Therapies against murine Candida guilliermondii infection, relationship between in vitro antifungal pharmacodynamics and outcome / Terapia antifúngica frente a la infección por Candida guilliermondii en ratones, correlación entre los parámetros farmacodinámicos in vitro y la eficacia in vivo

Background. Candida guilliermondii has been recognized as an emerging pathogen showing a decreased susceptibility to fluconazole and considerably high echinocandin MICs. Aims. Evaluate the in vitro activity of anidulafungin in comparison to amphotericin B and fluconazole against different isolates of C. guilliermondii, and their efficacy in an immunosuppressed murine model of disseminated infection. Methods. The in vitro susceptibility of four strains against amphotericin B, fluconazole and anidulafungin was performed by using a reference broth microdilution method and time-kill curves. The in vivo efficacy was evaluated by determination of fungal load reduction in kidneys of infected animals receiving deoxycholate AMB at 0,8 mg/kg i.v., liposomal amphotericin B at 10 mg/kg i.v., fluconazole at 50 mg/kg, or anidulafungin at 10 mg/kg. Results. Amphotericin B and anidulafungin showed fungicidal activity, while fluconazole was fungistatic for all the strains. In the murine model, liposomal amphotericin B at 10 mg/kg/day was effective in reducing the tissue burden in kidneys of mice infected with any of the tested strains. However, amphotericin B, anidulafungin and fluconazole were only effective against those strains showing low MIC values. Conclusions. Liposomal amphotericin B showed the higher activity and efficacy against the two strains of C. guilliermondii, in contrast to the poor effect of fluconazole and anidulafungin. Further studies with more isolates of C. guilliermondii representing a wider range of MICs should be carried out to assess whether there is any relationship between MIC values and anidulafungin efficacy (AU)

Antecedentes. Candida guilliermondii es un patógeno emergente, con reducida sensibilidad al fluconazol y a las equinocandinas. Objetivos. Evaluar la actividad in vitro de la anidulafungina, en comparación con la de la anfotericina B y el fluconazol, frente a C. guilliermondii y su eficacia en un modelo animal de infección diseminada. Métodos. La sensibilidad in vitro se valoró mediante microdilución en caldo y curvas de mortalidad. La eficacia in vivo se evaluó mediante la determinación de la carga fúngica en riñón de ratones inmunosuprimidos con infección diseminada por C. guilliermondii tratados con anfotericina B desoxicolato (0.8 mg/kg i.v.), anfotericina B liposomal (10 mg/kg i.v.), fluconazol (50 mg/kg) o anidulafungina (10 mg/kg). Resultados. La anfotericina B y la anidulafungina mostraron actividad fungicida, mientras que el fluconazol fue fungistático frente a todas las cepas. En el modelo murino, la anfotericina B liposomal redujo para todas las cepas la carga fúngica en riñones, mientras que la anfotericina B desoxicolato, la anidulafungina y el fluconazol fueron efectivas solo en aquellos animales infectados con las cepas de menor valor de concentración mínima inhibitoria (CMI). Conclusiones. La anfotericina B liposomal mostró la mayor actividad y eficacia frente a C. guilliermondii, en contraste con el limitado efecto del fluconazol y de la anidulafungina. Se necesitan estudios que incluyan cepas con un rango más amplio de CMI que permitan determinar la relación entre la actividad in vitro y la eficacia de la anidulafungina (AU)

Assessment of the quality of compounded fluconazole capsules marketed in the region of Araraquara (SP, Brazil) / Avaliação da qualidade de cápsulas de fluconazol manipuladas comercializadas na região de Araraquara (SP, Brasil)

O controle de qualidade de fármacos desempenha um papel importante na saúde pública ao garantir segurança e eficácia de medicamentos. No sistema de saúde pública,as farmácias magistrais também são importantes. Elas fornecem medicamentos personalizados como produtos dermatológicos e doses específicas para crianças.Infelizmente, muitos casos de produtos magistrais fabricados fora do padrão mínimo de qualidade têm sido relatados no Brasil. Neste trabalho, a qualidade das cápsulas magistrais de fluconazol 150 mg foi avaliada e os resultados foram comparados com os valores recomendados pela Farmacopeia Brasileira. Os resultados sugerem que é possível manipular produtos que satisfaçam as especificações farmacopeicas, mas estes ainda mostram que há farmácias magistrais onde o controle de qualidade é deficiente ou inexistente. O fluconazol é um fármaco importante no tratamento de infecções fúngicas. Seu uso como forma farmacêutica manipulada sem elevados padrões de qualidade é fortemente relacionado com a falha terapêutica e intoxicações, assim como o surgimento de microorganismos resistentes. Portanto, a necessidade de melhoria dos processos nas farmácias magistrais se torna mais enfático. Existem métodos validados que podem ser utilizados com sucesso para a análise de rotina de controle de qualidade e que podem ser implementados por qualquer farmácia de manipulação...

The quality control of drugs has an important role in public health, in ensuring the efficacy and safety of medicines. In the public health system, compounding pharmacies play a vital part. They provide medicines tailored to the individual patient, for example dermatological products and specific doses for children. Unfortunately, many cases of compounded products falling below the minimum quality standard have been reported in Brazil. In this study, the quality of compounded 150 mg fluconazole capsules was assessed and the results were compared with values stipulated in the Brazilian pharmacopoeia. The results suggest that, while it is certainly possible to prepare products meeting pharmacopoeial specifications, there are pharmacies where the quality control is deficient or nonexistent. Fluconazole is an important drug in combatting fungal infections. The use of fluconazole in dosage forms manufactured without high standards of quality control is strongly linked to treatment failure and cases of intoxication, as well as the emergence of resistant microorganisms. This highlights the urgent need for process improvement in compounding pharmacies. There are validated methods that can be successfully employed for routine quality control analysis that can be implemented by any compounding pharmacy...

Evaluation of the supply of antifungal medication for the treatment of vaginal thrush in the community pharmacy setting: a randomized controlled trial / Evaluación del suministro de medicación antifúngica para el tratamiento de la candidiasis vaginal en la farmacia comunitaria: ensayo controlado aleatorizado

Background: The Pharmaceutical Society of Australia have developed “guidance” for the supply of several medicines available without prescription to the general public. Limited research has been published assessing the effect of these guidelines on the provision of medication within the practice of pharmacy. Objectives: To assess appropriate supply of nonprescription antifungal medications for the treatment of vaginal thrush in community pharmacies, with and without a guideline. A secondary aim was to describe the assessment and counseling provided to patients when requesting this medication. Methods: A randomized controlled trial was undertaken whereby two simulated patients conducted visits to 100 randomly selected community pharmacies in a metropolitan region. A product-based request for fluconazole (an oral antifungal that has a guideline was compared to a product-based request for clotrimazole (a topical antifungal without a guideline). The same patient details were used for both requests. Outcome measures of the visits were the appropriateness of supply and referral to a medical practitioner. Results: Overall 16% (n=16) of visits resulted in an appropriate outcome; 10% (n=5) of fluconozaole requests compared with 22% (n=11) of clotrimazole requests (chi-square=2.68, p=0.10). There was a difference in the type of assessment performed by pharmacy staff between visits for fluconazole and clotrimazole. A request for clotrimazole resulted in a significant increase in frequency in regards to assessment of the reason for the request (chisquare= 8.57, p=0.003), symptom location (chisquare= 8.27, p=0.004), and prior history (chisquare= 5.09, p=0.02). Conclusions: Overall practice was poor, with the majority of pharmacies inappropriately supplying antifungal medication. New strategies are required to improve current practice of community pharmacies for provision of non-prescription antifungals in the treatment of vaginal thrush (AU)

Antecedentes: La Sociedad Farmacéutica de Australia ha desarrollado una “guía” para el suministro de varios medicamentos sin prescripción al público general. Se ha publicado poca investigación evaluando el efecto de estas guías sobre la provisión de medicación en la práctica de la farmacia. Objetivos: Evaluar el suministro apropiado de antifúngicos sin receta para el tratamiento de candidiasis vaginal en farmacias comunitarias, con y sin guía. Un objetivo secundario fue describir la evaluación y el consejo proporcionado a los pacientes cuando solicitaban esta medicación. Métodos: Se realizó un ensayo controlado aleatorizado donde dos pacientes simulados condujeron visitas a 100 farmacias comunitarias aleatoriamente seleccionadas en una región metropolitana. Se comparó una solicitud de un producto con fluconazol (antifúngico oral que tiene guía) con una solicitud de un producto con clotrimazol (un antifúngico tópico sin guía). Los mismos datos de los pacientes fueron usados en ambas solicitudes. Las medidas de resultados en las visitas fueron la adecuación del suministro y la remisión al médico. Resultados: Un total de un 16% (n=16) de las visitas produjeron resultados apropiados; 10% (n=5) de fluconazol comparadas con el 22% (n=11) de clotrimazol (chi-square= 2,68, p=0,10). Hubo una diferencia significativa en el tipo de evaluación realizada por el personal de la farmacia entre las visitas del fluconazol y del clotrimazol. La solicitud de clotrimazol produjo un aumento significativo en la frecuencia de la evaluación de la causa de la solicitud (chi-square = 8,57, p=0,003), localización de los síntomas (chi-square= 8,27, p=0,004), e historia previa (chi-square = 5,09, p=0,02). Conclusiones: En general la práctica fue pobre, con la mayoría de las farmacias suministrando inadecuadamente la medicación antifúngica. Se requieren nuevas estrategias para mejorar la práctica actual de las farmacias comunitarias en el suministro de antifúngicos sin receta para la candidiasis vaginal (AU)