UV SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE DETERMINATION OF BILASTINE USING EXPERIMENTAL DESIGN FOR ROBUSTNESS

Bilastine is a novel nonsedative H1-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). This study describes the validation of an UV spectrophotometric method for quantitative determination of bilastine in tablets using 0.1 mol L-1 HCl as solvent. The method was specific, linear, precise, exact and robust at 210 nm, confirming that the method is fast and useful to the routine quality control of bilastine in tablets. The validate method was compared to liquid chromatography (HPLC), which was previously developed and validated to the same drug, and no significative difference between the methods using Student´s t test was found to bilastine quantitation.Bilastine is a novel nonsedative H1-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). This study describes the validation of an UV spectrophotometric method for quantitative determination of bilastine in tablets using 0.1 mol L-1 HCl as solvent. The method was specific, linear, precise, exact and robust at 210 nm, confirming that the method is fast and useful to the routine quality control of bilastine in tablets. The validate method was compared to liquid chromatography (HPLC), which was previously developed and validated to the same drug, and no significative difference between the methods using Student´s t test was found to bilastine quantitation

Bilastine: stability-indicating a method using environmentally friendly by reversed-phase high-performance liquid chromatography (RP-HPLC)

This study describes the development and validation of a new environmentally friendly analytical method for the determination of bilastine in coated tablets and the evaluation of its capacity to be stability-indicating as well. The ecofriendly analytical method was validated by specificity, linearity, accuracy, precision and robustness by reversed-phase high-performance liquid chromatography (RP-HPLC) according to International Conference on Harmonization guidelines (ICH) and Association of Official Analytical Chemists (AOAC). Isocratic LC separation was achieved on a RP18 column using a mobile phase of sodium dihydrogen phosphate aqueous buffer solution adjusted to pH (6.0 ± 0.1) with o-phosphoric acid (85% v/v) and triethylamine (0,3% v/v) and ethanol (EtOH) in the following proportions (60:40 v/v), at a flow rate of 1.0 mL·min-1 at temperature-controlled at 30 °C. The analytical method showed selectivity, good recovery and precision (intra- and inter-day), robustness, and linear over a range from 5.0 to 50 μg·mL-1

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

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

Olmesartan medoxomil: validation of analytical methodology, biopharmaceutical evaluation, and polymorphic analysis

O pró-fármaco olmesartana medoxomila (OLM) é um anti-hipertensivo representante da classe dos bloqueadores seletivos dos receptores da angiotensina II (BRA). No Brasil, encontra-se disponível sob a forma de comprimidos revestidos (Benicar®). Foi aprovado pelo FDA em 2002. Não existe monografia disponível para este fármaco em nenhum código oficial. Desse modo, este trabalho objetivou o desenvolvimento de métodos analíticos para quantificação da OLM na substância química de referência (SQR) e forma farmacêutica, estabelecer a cinética de dissolução in vitro para os comprimidos revestidos deste fármaco e por fim investigar a presença de diferentes estruturas polimórficas da SQR deste anti-hipertensivo. A determinação da faixa de fusão, a espectrofotometria na região do infravermelho (IV), assim como a espectroscopia de ressonância magnética nuclear (RMN) de 1H e 13C permitiram a identificação da SQR. Os métodos por espectrofotometria na região do ultravioleta (UV), cromatografia em camada delgada (CCD), cromatografia a líquido de alta eficiência (CLAE) e cromatografia capilar eletrocinética micelar (MECC) foram utilizados para análise qualitativa do fármaco no produto acabado. A determinação quantitativa foi realizada através do desenvolvimento e validação de método indicativo da estabilidade por CLAE e MECC, avaliando-se os parâmetros descritos pelas guias de validação como: especificidade, robustez, linearidade, limites de detecção e quantificação, precisão e exatidão. Determinou-se ainda, a intercambialidade dos mesmos, através de análise estatística por ANOVA (p = 0,05), e comprovou-se que ambos podem ser utilizados para análise qualitativa e quantitativa da OLM em matéria-prima e produto acabado. O teste de dissolução foi desenvolvido e validado de acordo com o guia proposto pelo USP Fórum, utilizando como meio de dissolução 900 ml de uma solução a 0,5% (p/V) de lauril sulfato de sódio pH 6,8, a 37 ± 0,5 °C, pás a 50 rpm e quantificação por CLAE e espectrofotometria na região do UV. A análise do teor de OLM dissolvida, realizada por ambos os métodos, não apresentou diferença estatística (p > 0,05). Os perfis de dissolução do Benicar®, medicamento referência, e do Olmetec®, outra formulação disponível no mercado, foram considerados semelhantes, após aplicação do método modelo-independente (f1 e f2) e eficiência de dissolução. Avaliou-se, também, a cinética de dissolução de ambas as formulações através da aplicação de métodos modelo-dependentes. Os perfis de dissolução do Benicar® e Ometec® foram descritos pelos modelos propostos por Hixson-Crowell e de ordem zero, respectivamente. Os valores calculados para t50% e t80%, obtidos através da aplicação da equação de ordem zero, foram semelhantes aos valores experimentais encontrados no perfil de dissolução de ambos os produtos. As técnicas de espectrofotometria por reflexão difusa no IV com transformada de Fourier (ATRFTIR), difração de raios-X de pó (XRPD), calorimetria exploratória diferencial (DSC), termogravimetria (TGA) e microscopia eletrônica de varredura (MEV) permitiram a identificação de uma forma amorfa e outra polimórfica da SQR da OLM, diferentes daquela descrita na literatura. Logo, de acordo com os resultados obtidos, todos os métodos propostos podem ser utilizados para no controle de qualidade da OLM em SQR e produto acabado.The prodrug olmesartan medoxomil (OLM) is a selective angiotensin II receptor blocker (ARB). In Brazil, it is available as coated tablets (Benicar®). It was approved by FDA in 2002. There is no monograph available for this drug in any official code. According to this, the main purpose of this study was to develop a quality control analytical methodology for OLM in bulk material and dosage form, to establish in vitro dissolution kinetic for OLM coated tablets, and to investigate the crystalline behavior of OLM bulk material. The investigation of melting range and application of techniques such as infrared spectrophotometry (IR), as well as the 1H and 13C nuclear magnetic resonance (NMR) spectroscopy were used to identify OLM. Ultraviolet (UV) spectrophotometry, thin-layer chromatography (TLC), highperformance liquid chromatography (LC) and micellar electrokinetic chromatography (MEKC) were used for qualitative analysis of the drug in coated tablets. The quantitative determination was carried out through the development and validation of a stability-indicating LC and MEKC methods, evaluating the parameters described in the guidelines such as: specificity, robustness, linearity, detection and quantitation limits, precision, and accuracy. The results were compared statistically by ANOVA (p = 0.05), and no difference was found between them for both bulk material and coated tablets. A dissolution test was developed and validated according to the guideline proposed by the USP Forum, using 900 ml of dissolution medium containing 0.5% of sodium lauryl sulfate (w/V) pH 6.8, at 37 ± 0.5 °C, paddle at 50 rpm, and quantitation by LC and UV spectrophotometry. The resulting dissolution profiles did not show statistical difference (p > 0.05) between methods. The dissolution profiles of Benicar®, reference formulation, and Olmetec®, another commercial formulation available, were considered similar, using model independent (f1, f2, and dissolution efficiency) methods. The dissolution kinetic of both formulations, using model dependent approaches, revealed that Benicar® followed the Hixson-Crowell model, while Olmetec® the zero-order model. The calculated values of t50% and t80%, obtained from zero-order equation, were similar of experimental values found in the dissolution profile for both products. The attenuated total reflectance Fourier transformed infrared (ATR-FTIR) spectrophotometry, along with differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) allowed to identify one amorphous and other polymorphic forms of OLM. According to the obtained results, all proposed methods could be used in the quality control of OLM bulk material and coated tablets

Avaliação in sílico dos produtos de degradação do fármaco bilastina

Foi realizado uma pesquisa de literatura nos principais bancos de dados online, como Periódicos Capes, Google Acadêmico, Science Direct e Microsoft Academic, com o objetivo de pesquisar estudos de estabilidade e degradação forçada do fármaco para verificar se nos estudos encontrados haveria produtos de degradação formados e se tais produtos tiveram sua estrutura química elucidada

Development of dissolution method and comparative study of pharmaceutical solid forms containing Cetirizine

A cetirizina é um fármaco anti-histamínico encontrado no mercado brasileiro sob a forma de comprimidos e cápsulas magistrais. O presente estudo objetivou desenvolver um método de dissolução, bem como avaliar a qualidade biofarmacêutica de alguns produtos por meio de testes físicos e físico-químicos, tais como: variação de peso, desintegração, dureza, friabilidade, teor, uniformidade de conteúdo, teste e perfil de dissolução. No desenvolvimento do método de dissolução, diversas condições foram testadas e os seguintes parâmetros foram considerados satisfatórios: Ácido clorídrico 0,1 N (900 mL, a 37°C ± 0,5 °C) como meio de dissolução, aparato pá e cesta, respectivamente, para comprimidos e cápsulas, e rotação de 50 rpm. Realizou-se estudo comparativo de comprimidos provenientes de três laboratórios produtores diferentes, denominados de A (referência), B (genérico) e C (similar), bem como de cápsulas manipuladas por três diferentes farmácias, denominadas de D, E e F. Os produtos D e E, ambos cápsulas manipuladas, foram reprovados nos teste de dissolução e uniformidade de conteúdo, respectivamente. Todos os demais produtos apresentaram resultados satisfatórios nos testes a que foram submetidos.Cetirizine is an anti-histaminic drug available in the Brazilian market as tablets and compounded capsules. The present study aimed to develop a dissolution test and to evaluate the biopharmaceutical quality of some commercial products through physical and physical-chemical studies, such as: weigh variation, disintegration, hardness, friability, assay, content uniformity, dissolution test and dissolution profile. Several conditions were evaluated in the development of the dissolution test and the following parameters were considered satisfactory: Hydrochloric Acid 0.1 N 900 mL, at 37 °C ± 0.5 °C, as dissolution medium, paddle and basket apparatus for tablets and capsules, respectively, and 50 rpm of rotation. Comparative studies of tablets obtained from three different companies, denominated A (reference), B (generic) and C (similar), as well as capsules compounded by three different pharmacies, denominated D, E and E, were performed. The products D and E, both capsules, were reproved in the dissolution and content of uniformity tests, respectively. The other products showed satisfactory results in the applied tests.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of cetirizine in tablets and compounded capsules: comparative study between CE and HPLC

A capillary electrophoresis (CE) method was developed and validated for determination of cetirizine dihydrochloride in tablets and compounded capsules. The electrophoretic separation was performed in an uncoated fused-silica capillary (40 cm x 50 μm i.d.) using 20 mmol L-1 sodium tetraborate buffer (pH 9.3) as background electrolyte, a hydrodinamic sample injection at 50 mBar for 5 s, 20 KV applied voltage at 25 °C, and detection at 232 nm. The proposed method was compared with the high performance liquid chromatographic (HPLC) method previously validated for this drug, and statistical analysis showed no significant difference between the techniques