Search

Topical drug administration is frequently used for the treatment of vaginal candidiasis; however, most formulations using this route do not provide prolonged drug release. Our aim was to evaluate the antifungal efficacy of amphotericin B (AMB) and miltefosine (MFS) incorporated in nanocarriers for sustained drug release, in a murine model of vaginal candidiasis. AMB and MFS were incorporated in different topical formulations, namely: conventional vaginal cream (daily dose for 6 days; MFS-CR and AMB-CR groups), microemulsion that transforms into a liquid crystalline gel in situ (single dose, or in three doses, every 48 h; AMB-ME and MFS-ME groups) and alginate nanoparticles (single dose; MFS-AN group). Formulations were administered intravaginally in BALB/c female mice 24 h post-infection by Candida albicans yeasts. On the 7th day post-infection the animals were euthanized for mycological and histological analyses. Formulation persistence in the vaginal canal was assessed for 7 days by in vivo imaging, using nanocarriers labeled with Alexa-Fluor 647. AMB-ME(3×), MFS-ME(3×), and MFS-AN(1×) formulations were able to control fungal infection at comparable levels to those vaginal cream formulations. Notably, a single dose of MFS-AN was sufficient to reduce the fungal burden as effectively as MFS-ME(3×) and MFS-CR(6×). In vivo imaging showed that nanocarriers allowed prolonged antifungal activity by intravaginal administration reducing drug administration frequency. Therefore, AMB and MFS incorporated into a microemulsion and MFS encapsulated in alginate nanoparticles could be effective therapeutic alternatives for vaginal candidiasis, likely due to the sustained antifungal activity provided by these nanocarriers.

Objective To evaluate a pilocarpine spray as a treatment for xerostomia in patients treated with radiotherapy (RT) for head and neck cancer (HNC). Methods This was a placebo-controlled, double-blind, crossover clinical trial of patients complaining of dry mouth after RT for HNC. Forty patients were randomly assigned to either placebo or pilocarpine (1.54%) spray and instructed to use three times a day for 3 months. After 1-month washout period, patients were crossed over to receive placebo or pilocarpine. The assessments were salivary flow (Stimulated Whole Saliva Flow - SWSF), xerostomia (Xerostomia Inventory - XI), and quality of life (QoL/Oral Health Impact Profile - OHIP-14), assessed at baseline, 1 hr (only SWSF), and at 1, 2, and 3 months of treatment. Results Posttreatment SWFS was not statistically different between pilocarpine and placebo regardless of the treatment sequence (paired T test; p > .05), except for the SWFS rates at 2 months after therapy. When comparing pilocarpine with placebo in the time points, there was no significant difference (p > .05) for QoL or XI. Significant differences in improvement in QoL and xerostomia experience appeared along time for pilocarpine group. Conclusion The topical application of pilocarpine spray tested was similar to placebo on SWSF assessments in patients treated with RT for HNC.

Comparing the number of approvals granted for topical drug products by the FDA and by Anvisa, as well as the number of tests required by these and other international agencies at the time of registration, it becomes clear that the increased flexibility of the Brazilian regulatory requirements has resulted in a larger number of topical medicines on the market, without a guarantee of bioequivalence between the different formulations considered generic. For this reason, the aim of this study is to discuss, from the point of view of Brazilian researchers, the methodologies that could possibly be used in Brazil for the reasons mentioned above, the most urgent being a revaluation of Brazilian legislation concerning bioequivalence of these products. Among the approaches considered are: in vitro release test, in vitro permeation, pharmacodynamic test (only for corticoids), and dermatopharcokinetic and dermal microdialysis. We conclude that, firstly, based on the simplicity of the methods, as well as the ease for their implementation, parameters for the in vitro approach must be defined. Later, a wider discussion involving Anvisa, the scientific community and the industrial sector should be sought, aiming to assess the technical and economic viability of the adaptation to the Brazilian scenario in relation to the use of the in vivo methods discussed here. Comparando-se o número de registros concedidos para produtos tópicos pelo Food and Drug Administration (FDA) e pela Agência Nacional de Vigilância Sanitária (Anvisa) com o número de testes exigidos por essas e outras agências internacionais no momento do registro desses medicamentos, fica claro que a flexibilização das exigências regulatórias brasileiras vem proporcionando um maior número de medicamentos tópicos no mercado, sem que haja garantia da bioequivalência entre as diferentes formulações consideradas produtos genéricos. Diante disto, o objetivo deste trabalho é discutir, sob o ponto de vista do pesquisador brasileiro, as metodologias possíveis de serem utilizadas no Brasil para esta finalidade, considerando ser premente uma rediscussão da legislação brasileira no que concerne a bioequivalência destes produtos. Dentre as metodologias abordadas estão estudos de liberação e permeação in vitro, ensaio farmacodinâmico de branqueamento (exclusivo para os corticoides), dermatofarmacocinética e microdiálise dérmica. Concluímos que, inicialmente, baseados na simplicidade dos métodos, bem como na facilidade de implementação, parâmetros para a abordagem in vitro devem ser definidos. Posteriormente, uma discussão ampla envolvendo Anvisa, comunidade científica e segmento industrial deveria ser buscada, visando avaliar a viabilidade técnica e econômica de adequação à realidade brasileira, no emprego dos métodos in vivo, aqui discutidos.

A avaliação comparativa exigida para registro das formulações tópicas genéricas no Brasil é feita por meio do estudo de equivalência farmacêutica que avalia apenas os parâmetros físico-químicos e microbiológicos dos medicamentos. Internacionalmente, estudos clínicos ou farmacodinâmicos vêm sendo exigidos para comprovar a eficácia e a segurança das formulações genéricas tópicas semissólidas. Este trabalho apresenta uma comparação entre os diferentes requerimentos para registro de uma formulação tópica, considerando diferentes autoridades regulatórias, e faz um levantamento dos produtos tópicos dermatológicos registrados no Brasil até 2013. Tal levantamento demonstrou haver uma grande quantidade de cópias desse tipo de formulação no Brasil em comparação com os EUA. Este fato, associado à grande quantidade de estudos encontrados na literatura demonstrando bioinequivalência de medicamentos tópicos, evidencia a grande importância de uma readequação da legislação brasileira no que se refere aos requisitos técnicos para o registro de medicamentos genéricos e similares de aplicação tópica dermatológica no Brasil. The comparative evaluation required for the registration of generic topical medicines in Brazil is conducted by means of a pharmaceutical equivalence study, which merely assesses the physical/chemical and microbiological parameters of the formulations. At the international level, clinical or pharmacodynamic studies are now being required to prove the efficacy and safety of semisolid topical generic formulations. This work presents a comparison of the different requirements for the registration of topical formulations, taking into consideration the various regulatory authorities, and presents a survey of topical medicines registered in Brazil prior to 2013. The survey revealed that in comparison with the USA there were many more copies of these formulations registered in Brazil. This fact, together with the large number of studies in the literature showing the lack of bioequivalence of topical medication, is clear proof of the major importance of the need to realign Brazilian legislation with respect to the technical requirements for the registration of generic and similar medication for dermatological topical application in Brazil.