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The Brazilian generic drugs policy was implemented in 1999 with the aim of stimulating competition in the market, improve the quality of drugs and improve the access of the population to drug treatment. The process of implementing this policy allowed the introduction and discussion of concepts that had never before been used in the context of drug registration in Brazil: bioavailability, bioequivalence, pharmaceutical equivalence, generic drugs, biopharmaceutical classification system, biowaiver. The present article provides definitions for these concepts in the context of Brazilian legislation as well as a historical and chronological description of the implementation of the generic drugs policy in Brazil, including a list of current generic drug legislation. This article contributes to the understanding of the Brazilian generic drugs policy and facilitates the search for information concerning the legal requirements for registration of drugs in Brazil.

Simple and sensitive methods using high-performance liquid chromatography-diode array detection (HPLC-DAD) and ultraviolet (UV)-spectrophotometry were developed and compared to quantify lychnopholide (LYC) in poly-ε-caprolactone nanocapsules and to study its release kinetics. Both methods were validated concerning their specificity, linearity, limits of detection and quantification, precision, accuracy and stability. HPLC-DAD analyses were conducted using an RP C18 column, isocratic elution with a methanol-water (60:40 v/v) mobile phase at 0.8 mL/min flow rate and detection at 265 nm. The linear response (r(2) > 0.999) was obtained within a concentration range of 2-25 µg/mL using HPLC-DAD and 5-40 µg/mL using spectrophotometry. Intra-day and inter-day precision were obtained with low relative standard deviation values. The accuracy of the methods was within the range 98-101% for HPLC-DAD and from 96-100% for UV-spectrophotometry. Both methods were suitable to be applied for the determination of drug loading percentage (>96%) and encapsulation efficiency (>90%). Furthermore, the sensitivity of HPLC-DAD method allows studies of LYC release/dissolution in sink conditions. LYC presented 100% dissolution after 24 h, whereas only 60% of LYC was released from the nanocapsule dosage form, with no burst effect. The methods fulfilled all validation parameters evaluated for LYC quantification in the polymeric nanocapsules and have proven to be accurate, selective and sensitive in the previously mentioned applications.

Fármacos contidos em formas farmacêuticas sólidas devem ter

ABSTRACTA combination of drugs in experimental chemotherapy of Chagas' disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2β) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0-∞), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole againstTrypanosoma cruzi in vivo.

The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate.

Recebido em 5/1/10; aceito em 18/4/10; publicado na web em 9/8/10 PHYSICOCHEMICAL CHARACTERIZATION OF ANTICHAGASIC BENZNIDAZOLE. Currently, benznidazole (BNZ) is a unique therapeutic alternative available in Brazil to treat Chagas disease. Despite its traditional medical use, little is known about the chemical nature of this drug. A detailed study of the physicochemical properties of BNZ was performed using multiple assays. Thermal, diffractometric, morphological and reological drug profiles were obtained. The partition coefficient and solubility results allowed this drug to be classified as a class IV drug according to the biopharmaceutical classification system. This information will be useful for the development of more effective BNZ formulations and for establishing the quality profile of BNZ.Keywords: benznidazole; preformulation; biopharmaceutical classification. INTRODUÇÃOA pesquisa e o desenvolvimento de medicamentos inovadores têm sido uma empreitada cada vez mais cara e complexa, o que torna mais escassa a introdução de novas moléculas no mercado. Estima-se que de cada 30.000 compostos sintetizados, apenas 0,003% chegam a se tornar fármacos disponíveis no comércio. 2Dentre as causas que explicam estes inúmeros fracassos estão problemas derivados de sua biodisponibilidade e toxicidade, que podem estar relacionados ao escasso conhecimento acerca da natureza da molécula em estudo. 3Neste contexto, os estudos de pré-formulação, realizados nas etapas de pesquisa pré-clínica e clínica de fármacos inovadores, e que visam acumular o máximo de informação sobre o comportamento das novas entidades químicas, constituem um valioso instrumento para traçar estratégias de desenvolvimento racional de formulações mais eficazes e seguras e, portanto, com maiores possibilidades de êxito. 4,5 Diversos aspectos concernentes à substância ativa, como a biodisponibilidade a partir da forma farmacêutica, ou ao medicamento, como seu prazo de validade, e até mesmo seu processamento industrial são afetados pelas propriedades físico-químicas dos fármacos.O Benznidazol [BNZ] (N-benzyl-2-nitro-1-imidazole-acetamide) (Figura 1), constitui um dos únicos recursos terapêuticos disponíveis no combate à doença de Chagas há décadas. Este medicamento é bastante efetivo na fase aguda da doença, mas existem relatos de baixa ou nenhuma eficácia na fase crônica. Efeitos secundários severos associados à utilização desse fármaco têm sido reportados, tendo como consequência, a interrupção do tratamento medicamentoso. Apesar de ser um fármaco já consolidado no mercado e bastante estudado do ponto de vista farmacológico, as propriedades físico-químicas do BNZ são praticamente desconhecidas. Estudos de pré-formulação poderiam propiciar uma maior compreensão das suas características biofarmacêuticas e permitir vislumbrar alternativas para melhorar sua ação terapêutica.Desta forma, o objetivo deste estudo foi traçar o perfil físico-químico do BNZ através de diferentes ensaios de caracterização, como forma de estabelecer parâmetros de qualidade para est...

Objective:to characterize and determine the polypharmacy prevalence in patients with chronic diseases and to identify the factors associated, in order to improvement of pharmaceutical care focused on patient safety.Methods:cross-sectional study included 558 patients, covered by primary health care, using a household and structured questionnaire. We analyzed the data on polypharmacy and its clinical and socioeconomic factors. Poisson regression analysis with robust variance was applied, with results expressed in prevalence ratio.Results:the results showed that polypharmacy (consumption of four or more drugs) was of 37.6%. The prevalence ratio analyses identified independent variables associated with polypharmacy: age (3.05), economic strata (0.33), way of medication acquisition through a combination of out-of-pocket and Brazilian public health system (1.44), diabetes and hypertension (2.11), comorbidities (coronary artery disease 2.26) and hospital admission (1.73). In the analyses, inappropriate medication use of the 278 patients (≥ 65 years) was associated with polypharmacy (prevalence ratio 4.04).Conclusion:polypharmacy study becomes an opportunity to guide the strategies for the patient safety to promote the medication without harm in chronic diseases.