New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms / 药物分析学报

Tioconazole (TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses. The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal (differential scanning calorimetry (DSC), melting point, and thermogravimetry (TG)), spectroscopic (ultraviolet (UV), Raman, near infrared (NIR), infrared spectroscopy coupled to attenuated total reflectance (FTIR-ATR), and nuclear magnetic resonance (NMR)), microscopic and X-ray diffraction (XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size dis-tribution (3–95 mm) resolved by microscopic measurements. TCZ melting point (82.8℃) and a de-gradation peak centered at 297.8 ℃ were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono- and two- dimensional 1H and 13C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate tech-niques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.

Diseño y preparación de formas farmacéuticas sólidas de Benznidazol para el tratamiento de la Enfermedad de Chagas / Design and Preparation fo Pharmaceutical Solid Dosage Forms of Benznidazole for the Treatment of Chagas Disease

INTRODUCCIÓN: En Argentina se emplea el benznidazolcomo terapéutica de primera línea para el tratamiento etiológico del Chagas. Desde su lanzamiento (hace más de 40 años), sólo se dispone de comprimidos convencionales de 100 mg; no se han desarrollado nuevas formas farmacéuticas que aumenten la eficacia y seguridad, ni alternativas con dosis pediátricas. OBJETIVOS: Desarrollar formas farmacéuticas de benznidazol que ofrezcan ventajas farmacoterapéuticas. MÉTODOS: Preformulación y diseño de nuevas formulaciones de benznidazol, con caracterización físico-química y selección de las formulaciones más favorables. Frente a la discontinuidad de producción del ingrediente activo benznidazol, se desarrolló una metodología de extracción a partir de 8520/8520/nica alternativa comercial disponible. RESULTADOS: Se obtuvieron nuevas formulaciones de comprimidos de 50 y 100 mg debenznidazol, con una rápida disolución del producto de referencia. Además, se obtuvieron formulaciones masticables de 50 mg bajo la forma de hidrogeles azucarados, con un efectivo enmascaramiento del mal sabor. Todas las formulaciones cumplieron los ensayos de evaluación de las propiedades farmacotécnicas y biofarmacéuticas, superando los perfiles de referencia. CONCLUSIONES: Se desarrollaron nuevas alternativas farmacéuticas de benznidazol de rápida disolución, que podrían mejorar el tratamiento etiológico de la enfermedad(especialmente en pediatría) y convertirse en herramientas aptas para su explotación comercial

INTRODUCTION: In Argentina, benznidazole is the drug of choice for the etiological treatment of Chagas disease. Since it was launched (more than 40 years ago), there are only 100 mg tablets available; the development included neither new pharmaceutical forms improving efficacy and safety, nor a pediatric dosage option. OBJECTIVES: To develop pharmaceutical form sof benznidazole with pharmacotherapeutic advantages. METHODS: Preformulation and design of new formulation sof benznidazole, with physicochemical characterization and selection of the most favorable formulations. Due to the discontinuity in the production of the active ingredient benznidazole, a specific methodology was developed in order to obtain it from the only commercially available alternative. RESULTS: New benznidazole tablet formulations were obtained (50 and 100 mg), with a rapid dissolution of the reference product, as well as chewable formulation sof 50 mg as sugar hydrogels featuring an effective taste masking. All formulations passed the evaluation tests for pharmacotechnical and biopharmaceutical properties, out performing the reference profiles. CONCLUSIONS:New fast-dissolving pharmaceutical dosage forms of benznidazole were developed, which could improve the etiological treatment of the disease (especially in the pediatric field) and become a proper tool for its commercial exploitation

Recentes avanços no tratamentoda doença de Chagas / Recent advances in the treatment of Chagas disease

Descoberta há cem anos, a doença de Chagas afetaa mais de quinze milhões de pessoas em toda aAmérica Latina e, ainda hoje, não há tratamentoeficaz. O fármaco benznidazol, utilizado como únicaopção de tratamento no Brasil, é ineficaz na fasecrônica da doença. Problemas relacionados à biodisponibilidadedo medicamento comercial limitam suaeficácia, principalmente na fase crônica, quando osparasitos estão confinados em tecidos profundos eem lenta replicação. Nesse contexto, pesquisas lideradaspor grupos brasileiros e argentinos vêm sendoconduzidas com o objetivo de desenvolver formulaçõesde benznidazol mais eficientes. Diversas formasfarmacêuticas sólidas e líquidas foram propostas nosúltimos anos com resultados pré-clínicos promissores,sendo descritas melhorias acentuadas nas característicasfarmacocinéticas desse fármaco. Espera-seque as formas inovadoras apresentadas possam seravaliadas em ensaios clínicos e incorporadas à produçãoindustrial em breve.

Discovered about a hundred years ago, Chagas diseasecurrently affects more than fifteen million people in LatinAmerica, and it still remains without any effective treatment.Although benznidazole has been used as the onlypharmacotherapeutic option to treat Chagas disease inBrazil, it is ineffective in the chronic phase of the disease,when the parasites are confined to deep tissue layers andslowly replicate. This happens mainly due to problems related to the bioavailability of the drug, which is currentlyin the market. In this context, Brazilian and Argentineanresearch groups have conducted studies to develop moreefficient benznidazole formulations. Several solid andliquid formulations have been proposed over the last fewyears with promising preclinical results. Improvementsin the pharmacokinetic properties of this drug have beendescribed. Therefore, it is expected, that such innovative drugs and formulations be assessed in clinical trials andsoon incorporated to industrial production.