ABSTRACT
SUMMARY Aim: A new stability-indicating liquid chromatography method was developed and validated for the quantitative determination of luliconazole. Materials and methods: Preliminary forced degradation study demonstrated an additional peak of the degradation product at the same retention time to the drug, due to this, the method was developed optimizing the chromatographic conditions to provide sufficient peak resolution (R ≥ 2). The experimental design was evaluated to assess the robustness and the best chromatographic conditions to be used for the validation. Methodology: Luliconazole solutions were exposed to various stress conditions to evaluate the method indication stability, in which the degradation product (DP-1) formed was isolated, identified, and evaluated in silico to predict degradation pathway and toxicity. The procedure was validated by robustness, selectivity, linearity, precision, and accuracy. Liquid chromatography was performed in a Phenomenex® RP-18 column with a mixture of acetonitrile and 0.3% (v/v) triethylamine solution as a mobile phase in isocratic elution. Results and conclusions: The method demonstrated robustness, good recovery, precision, linear response over a range from 5.0 to 40.0 μg.mL-1- and to be stability indicating. The alkaline stress condition resulted in the formation of DP-1. HRMS studies identified this product as an hydroxyacetamide derivative, and in silico studies did not show toxic potential.
RESUMEN Objetivo: Un nuevo método indicativo de estabilidad por cromatografía líquida fue desarrollado y validado para la determinación cuantitativa de luliconazol. Materiales y métodos: Estudios preliminares de degradación forzada demostraron un pico adicional en el mismo tiempo de retención del fármaco. El método desarrollado para optimizar las condiciones cromatográicas proporcionó una adecuada resolución (R ≥ 2). El diseño experimental fue evaluado para verificar su robustez y la mejor condición cromatográica para validación. Metodología: Las soluciones de luliconazol fueron expuestas a diferentes condiciones de estrés para evaluar la indicación de estabilidad del método, el aislamiento del producto de degradación formado (DP-1), su identificación y análisis in silico para predecir su ruta de degradación y toxicidad. El procedimiento se validó por robustez, selectividad, linealidad, precisión y exactitud. Las condiciones cromatográficas incluyeron una columna Phenomenex® RP-18, como fase móvil una mezcla de acetonitrilo y solución 0,3% (v/v) de trietilamina en elución isocrática. Resultados y conclusiones: El método mostró ser robusto, con buena recuperación, precisión, respuesta lineal en el rango de 5,0 a 40,0 μg.mL-1 e indicativo de la estabilidad. La condición de estrés alcalina resultó en la formación de DP-1. Estudios por HRMS identificaron este producto como un derivado hidroxiacetamida y los estudios in silico no mostraron potencial de toxicidad.
RESUMO Objetivo: Um novo método indicativo de estabilidade por cromatograia líquida foi desenvolvido e validado para a determinação quantitativa de luliconazol. Materiais e métodos: Estudos preliminares de degradação forçada demonstraram um pico adicional no mesmo tempo de retenção do medicamento. O método desenvolvido para otimizar as condições cromatográficas proporcionou resolução adequada (R ≥ 2). O delineamento experimental foi avaliado para verificar sua robustez e a melhor condição cromatográica para validação. Metodologia: Soluções de luliconazol foram expostas a diferentes condições de estresse para avaliar a indicação da estabilidade do método, o isolamento do produto de degradação formado (DP-1), sua identificação e análise in silico para predizer sua rota de degradação e toxicidade. O procedimento foi validado quanto à robustez, seletividade, linearidade, precisão e exatidão. As condições cromatográficas incluíram uma coluna Phenomenex® RP-18, como fase móvel uma mistura de acetonitrila e solução de trietilamina 0,3% (v/v) em eluição isocrática. Resultados e conclusões: O método mostrou-se robusto, com boa recuperação, precisão, resposta linear na faixa de 5,0 a 40,0 μg.mL-1 e indicativo de estabilidade. A condição de estresse alcalino resultou na formação de DP-1. Os estudos da HRMS identificaram este produto como um derivado da hidroxiacetamida e os estudos in silico não mostraram nenhum potencial de toxicidade.
ABSTRACT
ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.
Subject(s)
Plant Oils/analysis , Plant Oils/pharmacology , Anacardiaceae , Emulsions/pharmacologyABSTRACT
Liquid chromatographic method was developed and validated for quantitative determination of quinine in polymeric nanoparticles. The method was performed using a Waters RP-18 column using a mobile phase consisting of acetonitrile:water:triethylamine (60:40:0.01 v/v/v, and pH aqueous phase adjusted to 3.0 with phosphoric acid). The flow rate was 1.0 mL min-1 and the detection was achieved with a UV-PDA set at 232 nm. The response was linear over a range of 12.0 to 24.0 μg.mL-1 (r = 0.9995). The relative standard deviation values for intra-day and inter-day precision studies were less than 2% and the accuracy was 98.8% to Nc1 and 97.3% to Nc2. The samples free of quinine and quinine-loaded polymeric nanoparticles were subjected to photodegradation conditions. A considerable reduction of degradation of quinine occurred in polymeric nanoparticles. Through these results, it was clear that the nanoencapsulation of quinine protects the drug from degradation by exposure to UV-A light. The analytical method was validated according to International Conference on Harmonization Guidelines and Center for Drug Evaluation and Research.
ABSTRACT
Dodonaea viscosa Jacq., Sapindaceae, é uma planta tradicionalmente utilizada como antifebril, anti-reumática e antimicrobiana. Neste trabalho foram determinados parâmetros morfo-anatômicos, por análise macro e microscópicas, das folhas de Dodonaea viscosa, com o objetivo de auxiliar sua diagnose como insumo farmacêutico. Macroscopicamente as folhas apresentam limbo com forma lanceolada, margem inteira, consistência áspera e venação eucamptódroma. O pecíolo é curto, reto e em seção transversal é triangular com os ângulos arredondados. Microscopicamente destaca-se a cutícula com formações lenticulares, os tricomas glandulares com quatro células na base, os tricomas tectores unicelulares de ápice afilado, os estômatos higrofíticos dispostos apenas na face abaxial da epiderme, o parênquima paliçádico com até três camadas de células e os feixes vasculares com xilema envolto por floema e cordões de parênquima que ligam um maciço central de células de parênquima a uma bainha de esclerênquima. Estas características morfo-anatômicas, quando analisadas em conjunto, contribuem no controle botânico de qualidade das folhas de Dodonaea viscosa como insumo farmacêutico.
Dodonaea viscosa Jacq., Sapindaceae, is a plant traditionally used as anti fever, anti- rheumatic and antimicrobial. This work determined morpho-anatomical parameters, by macro and microscopic analysis of Dodonaea viscosa leaves, aiming to reach their diagnosis as pharmaceutical input. Macroscopically, the leaves have a lanceolate shape limb, full margin, rough consistence and venation eucamptodromous. The petiole is short, straight and in transversal section it is triangular with round angles. Microscopically, the lenticullar formation cuticle is seen with prominence, the glandular thricomes are seen with four cells on the base, the non-glandular unicellular thricomes are seen with pointed apex, the higrophitic stomatas are disposed in the lower surface epidermis only, the palisade parenchyma show up to three-cell layers and vascular bundles with xylem involved by phloem and parenchyma lines which bound a central mass of parenchyma cells to a sclerenchyma sheath. This morph-anatomical characteristic, when analyzed in group, contributes to the botanical quality control of Dodonaea viscosa leaves as pharmaceutical input.