The Evaluation of Valsartan Biopharmaceutics Properties.

BACKGROUND: Solubility, intestinal permeability and dissolution are the main factors that govern the rate and extent of drugs absorption and are directly related to bioavailability. Biopharmaceutics Classification System (BCS) is an important tool which uses in vitro results for comparison with bioavailability in vivo (biowaiver). Valsartan is widely used in the treatment of hypertension and shows different BCS classification in the literature (BCS class II or III). OBJECTIVE: This work proposes the study of valsartan biopharmaceutics properties and its BCS classification. METHODS: High Performance Liquid Chromatography (HPLC) method was developed and validated to quantify the drug in buffers pH 1.2, 4.5 and 6.8 respectively. Valsartan solubility was determined in these three different media using shake flask method and intrinsic dissolution rate. Evaluation of dissolution profile from coated tablets was conducted. RESULTS: The low solubility (pH 1.2 and 4.5) and high solubility (pH 6.8) were observed for both solubility methods. Permeability data reported from the literature showed that valsartan is a low permeability drug. Valsartan presented the rapid release profile only in pH 6.8. CONCLUSION: We defined that valsartan is a class IV drug, in disagreement with what has been published so far. It is important to emphasize that the conditions considered here are indicated to define the biopharmaceutics classification by regulatory agencies.

Effect of pyridostigmine on in vivo and in vitro respiratory muscle of mdx mice.

The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.

Acute and sub chronic toxicity study of aqueous extract from the leaves and branches of Campomanesia velutina (Cambess) O. Berg.

ETHNOPHARMACOLOGICAL RELEVANCE: Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively. AIM OF THE STUDY: Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie. MATERIALS AND METHODS: In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária - ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests. RESULTS: In oral acute assay, treatment with AEB at the major dose (1200mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300mg/kg and AEB 600 and 1200mg/kg as well as in females treated with AEB 300 and 1200mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600mg/kg, AEL 1200mg/kg and AEB 1200mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain and the relative weight of males' brain was increased on group treated with AEL 300mg/kg, AEB 300 and AEB 1200mg/kg. Although changes in hematological parameters were not observed, serum creatinine levels were significantly higher in males treated with AEB 300mg/kg. Besides, the heart of all treated animals showed intense hyperemia. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins and phenolic compounds. CONCLUSIONS: Toxicity signs were mainly observed after treatment with AEL and AEB at the two highest tested doses (600 and 1200mg/kg), suggesting that the extracts are relatively safe at its effective dose (300mg/kg). However, alterations on hematological and biochemical parameters and on the kidney and heart of the animals were not closely related with the dose, implying caution on its use.

Medicamentos genéricos no Brasil: panorama histórico e legislação / Generic drugs in Brazil: historical overview and legislation

A política de medicamentos genéricos foi implantada no Brasil em 1999 com o objetivo de estimular a concorrência comercial, melhorar a qualidade dos medicamentos e facilitar o acesso da população ao tratamento medicamentoso. O processo de implementação dessa política permitiu a introdução e a discussão de conceitos nunca antes utilizados para o registro de medicamentos no Brasil: biodisponibilidade, bioequivalência, equivalência farmacêutica, medicamentos genéricos, sistema de classificação biofarmacêutica e bioisenção. Este artigo apresenta a definição desses conceitos no contexto das leis brasileiras e oferece uma descrição histórica e cronológica da implementação da política de genéricos no Brasil, listando ainda as resoluções que atualmente estão em vigor. Os resultados contribuem para a compreensão do processo e facilitam a busca e a identificação de ensaios necessários para satisfazer os critérios legais.

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.

[Generic drugs in Brazil: historical overview and legislation]. / Medicamentos genéricos no Brasil: panorama histórico e legislação.

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.