Preparation and Quality Evaluation of Butenafine Hydrochloride Thermosensitive Microemulsion-Based Hydrogel / 中国药学杂志

OBJECTIVE: To prepare butenafine hydrochloride thermosensitive microemulsion-based hydrogel and evaluate the quality. METHODS: A series of temperature sensitive microemulsion gels with different gelation temperatures were prepared, using ethyl oleate as oil phase, Tween 80 as surfactant, ethanol as co-surfactant, and poloxamer as temperature-sensitive material. The morphology, particle size, Zeta potential, percutaneous absorption speed and skin retention were evaluated. RESULTS: The best formulation was composed of ethyl oleate-Tween 80-ethanol-poloxamer 407-poloxamer 188-distilled water at ratios of 4∶15∶10∶16.33∶5.68∶71. The oil/water microemulsion exhibited a spherical shape without adhesion or aggregation observed by TEM. The average diameter was 91.03 nm and the PDI was 0.246. The transdermal speed of microemulsion gel was faster than the marketed cream, and the drug retention in the skin was 5 times of the marketed cream. CONCLUSION: The hydrogel exhibits good temperature sensitivity and skin retention effect, and can penetrate skin cutin and act as a depot thus increase the local drug concentration and enhance the antibacterial effect.

Investigation of preparation and quality control for butenafine hydrochloride plastics / 中国生化药物杂志

Objective To prepare butenafine hydrochloride plastics,investigate the prescription composition and make a quality control standard for the preparation.Methods Film-forming time and appearance quality as the evaluation index,the quality control standard of butenafine hydrochloride according to the Chinese pharmacopoeia two section ( 2010 edition ) was made.ResuIts The prescription of butenafine hydrochloride plastics was identified as:1%butenafine hydrochloride(w/w),10%glycerol(w/w),3%carbomer 971PNF(w/w),0.1% ethyl p-hydroxybenzoate(w/w),moderate anhydrous sodium sulfite(pH adjusting agent) and 95% ethanol (solution).The preparation was colorless,transparent and viscous semi-solid with pH4.5.A content determination method of butenafine hydrochloride with HPLC was established and the result was stable and reliable .ConcIusion The butenafine hydrochloride has several advantages such as preparation simply , stable property,application convenience and quality control.It is a potential preparation to develop.

Avaliação da eficácia in vitro de butenafina ante os agentes de micoses cutâneas prevalentes no Brasil / Evaluation of in vitro efficacy of butenafine on the more prevalent cutaneous mycosis in Brazil

O tratamento de micoses cutâneas é realizado com antifúngicos orais ou tópicos. A butenafina, da classe das benzilaminas, é um novo medicamento de uso tópico com eficácia clínica comprovada em casos de dermatomicoses. O objetivo desse estudo foi investigar a atividade ?in vitro? da butenafina em dermatófitos, outros filamentosos ou leveduras, agentes de micoses de pele e unha e compará-la a outros três antifúngicos isoconazol, ciclopirox olamina e oxiconazol. A suscetibilidade aos antifúngicos foi avaliada por métodos de referência de microdiluição M38-A2 (NCCLS, 2002) e M27-A3 (CLSI-2008) para determinação da concentração inibitória mínima (MIC). Um método de triagem por disco-difusão (M44-A, CLSI, 2002) foi avaliado diante dos padrões, com vistas a sua utilização em laboratórios de rotina. Discos contendo as drogas antifúngicas foram preparados em concentrações de 0,125 a 100 µg e ensaiados, em duplicata contra todas as amostras de fungos, e os resultados foram comparados com o valor de MIC correspondente à dupla antifúngico-espécie. O disco na concentração de 2 mg permitiu identificação de perfis distintos de sensibilidade à butenafina, sendo indicado para uso em rotina. A maioria (64%) das espécies, incluindo dermatófitos (Trichophyton mentagrophytes, T. rubrum, T. violaceum, Microsporum canis), fungos não dermatófitos (Scytalidium lignicola, Fusarium) e leveduras (Candida glabrata, C.guilliermondii, C.parapsilosis), foi inibida em baixas concentrações (MIC 0,25 mg/mL), correspondendo a halos de inibição de até 60mm de diâmetro frente a butenafina. Para ciclopirox, a maioria (72%) das espécies não formou halo de inibição, com MICs acima de 0,25 µg/mL melhor resultado foi obtido com T. violaceum (MIC 0,06 mg/mL, halo 20 mm). A maior eficácia (100% de inibição) contra dermatófitos foi observada em butenafina e isoconazol oxiconazol inibiu 88,9% das amostras de dermatófitos com menor desempenho ante a T. mentagrophytes. Butenafina, isoconazol e oxiconazol foram mais ativas do que ciclopirox frente aos dermatófitos, quando verificadas as concentrações necessárias para inibir 50% e 90% (MIC50 e MIC90) das amostras. Agentes oportunistas, S. lignicola e Aureobasidium pullulans, foram sensíveis à butenafina, isoconazol e oxiconazol, não sendo inibidos por ciclopirox. Butenafina foi a única droga capaz de inibir, em baixas concentrações (MIC 0,25 mg/mL halo 14 mm), as duas amostras de Fusarium spp., fungo filamentoso não dermatófito de difícil controle terapêutico, principalmente, nos casos de onicomicose persistente os outros antifúngicos ensaiados apresentaram MIC acima de 16 mg/mL para esse gênero. Para Candida albicans, observou-se que butenafina, em altas concentrações, apresentou atividade inibitória maior se comparada a ciclopirox. Conclui-se que discos com 2 mg de butenafina permitem a classificação de fungos, filamentosos e leveduras, em categorias distintas de suscetibilidade, sendo útil para testes de triagem de cepas menos sensíveis, desde que mostrou boa correlação com os métodos de referência. Os testes de sensibilidade in vitro comprovaram a alta eficiência de butenafina contra agentes de micoses cutâneas, em particular, contra os principais agentes: dermatófitos. Estudos de correlação clínico-laboratorial poderão contribuir para um futuro consenso de critério interpretativo para valores de MIC de butenafina, definindo pontos de corte de sensibilidade.

A Randomized,Double-Blind,Multi-Center Clinical Trial with Butenafine Hydrochloride 1% Aerosol Versus Bifonazole 1% Aerosol for the Treatment of Tinea Pedis,Tinea Corporis or Tinea Cruris / 中华皮肤科杂志

Objective To investigate the efficacy and safety of butenafine hydrochloride 1% aerosol in the treatment of tinea pedis,tinea cruris or tinea corporis.Methods A randomized,double-blind,multi-center clinical trial was conducted.Efficacy was assessed in terms of mycological cure,total clinical sign and symptom scores,and clinical response,at baseline,mid-term,end of study,and 2 weeks after treatment.Results One hundred and seventeen patients with tinea cruris or tinea corporis were randomly allocated to individual groups treated with either butenafine 1% aerosol (n = 58,male 53,female 5,age 29.45 ? 11.80,course of disease 3.0 ? 5.0 months) or bifonazole 1% aerosol (n = 59,male 49,female 10,age 34.12 ? 12.98,course of disease 3.0 ? 11.0 months).One hundred and nineteen patients with tinea pedis were also allocated to two groups treated with either butenafine (n = 59,male 59,age 22.97 ? 3.97,course of disease 24.0 ? 36.0 months) or bifonazole (n = 60,male 60,age 23.77 ? 4.12,course of disease 36.0 ? 48.0 months).The cure rates and total response rates were 25.86% vs.40.68%,and 86.21% vs.91.53%,in the study group and the control group,respectively,at the end of study,and 58.62% vs.74.58%,and 96.55% vs.96.61% in 2 weeks following-up,for the patients with tinea cruris or tinea corporis.Also,the cure rates and total response rates were 23.73% vs.25.00%,81.36% vs.78.33%,in the study group and the control group,respectively,at the end of study,and 37.29% vs.41.57% and 81.36% vs.90.00% in 2 weeks following-up,for the patients with tinea pedis.Local adverse reactions were recorded in 13 of butenafine group,and 20 of bifonazole group.The differences of above data between two groups were not statistically significant.Conclusion Butenafine hydrochloride 1% aerosol is effective and well tolerated for the treatment of tinea pedis,tinea cruris or tinea corporis.

Efficacy of 1 % Butenafine Hydrochloride Cream in the Treatment of Tinea Pedis / 대한피부과학회지

BACKGROUND: Topical 1% butenafine hydrochloride cream, a new benzylamine derivative, has been reported to have antimycotic effect. OBJECTIVE: An open trial as conducted to assess the efficacy and safety of 1% butenafine hydrochloride cream used once daily in the treatment of tinea pecis. METHODS: Of 45 patients with clinically and mycologically proertinea pedis from the department of dermatology at Kosin medical college hospital, 42 patient, who could be monitored to the end of this study were evaluated. They applied 1% butenafine hydrochloride cream once daily until clinical improvement became evident or for 4 weeks and the effects were evaluated clinically and mycologically. RESULTS: 1. From the mycological studies at the initial visit, causative organisms were isolated from 36 patients out of the 42 subjects and Trichophyton rubrum was most comnmon organism. 2. The negative conversion rate of the mycological study( negative microscopy and negative culture) was 90.5%(38/42) after 4 weeks of treatment. 3. The effective treatment vate at 4 weeks was 90.5%(38/42) 4. A adverse effects of using 1% butenafine hydrochloride cream was noted in 1 patient, who had a moderate degree of puritus, out of the 42 subjects. The presritus disappeared soon after the cessation of application of the cream. CONCLUSION: 1% butenafine lydrochloride cream is effective andafe in the treatment of tinea pedis.