André Luís Gemal

Caracterização de polimorfismo em fármacos por ressonância magnética nuclear no estado sólido

This review aims to present some features about solid state NMR and its application in the field of pharmaceutical chemistry, for the characterization of polymorphism of pharmaceutical molecules.

Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges

BackgroundDespite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs.DiscussionQuality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product´s safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are expected in a close future.SummaryInternational manufacturers of raw material for tuberculosis treatment should undergo certification and pre-qualify their active pharmaceutical ingredients as a first step to ensure quality of tuberculosis drugs. At the country level, Brazilian public manufacturers should apply for international certification and tuberculosis drugs should be pre-qualified by international organisms. Finally, only with political commitment and large-scale production will Brazilian public sector manufacturers be able to partially supply the global market.

Resultados do controle de qualidade de produtos hemoderivados: análise sanitária

The technical scientific unit of the National Institute of Quality Control in Health (INCQS), part of the Oswaldo Cruz Foundation, has a role of investigational quality control of products and services related to health surveillance, in particular medicines denominated plasma derivative products. This paper is based on the analysis of the 3100 plasma derivative products from January 2000 to December 2004: 31.6% (n=980) of human albumin, 28.7% (n=890) of factor VIII, 21.4% (n=662) of human immunoglobulins, 8.3% (n=257) of factor IX, 7.1% (n=22) of specific immunoglobulin classes containing anti-Rho (D) immunoglobulin, anti-hepatitis B, anti-tetanus, anti-rabies and anti-varicella-zoster and 2.91% (n=91) of prothrombin complex. The products submitted to analysis came from airports and frontiers of Brasilia, Rio de Janeiro and Sao Paulo, and products confiscated by the states of Pernambuco, Santa Catarina, Rio de Janeiro and Rio Grande do Sul. The type of analysis was characterized as: 92.3% control analysis; 5.9% fiscal analysis; 1.4% guidance and 0.4% preliminary analysis. In respect to imported plasma derivatives, 40.0% originated from the airport in Brasilia, 26.9% in Sao Paulo and 25.2% in Rio de Janeiro. In conclusion, 99.1% of the plasma derivative products analyzed was considered satisfactory and 0.9% unsatisfactory as identified by visual inspection, solubility, stability and chemical assays and pyrogenic and unspecific toxicity tests. Thus, the assessment of the quality of plasma derivative products is an essential tool for health surveillance.

Solid-state 13C nuclear magnetic resonance spectra of 6-aminopenicillanic acid

The 13C and 1H13C cross-polarization magic-angle spinning (CP-MAS) spectra of 6-aminopenicillanic acid are reported.

Adverse events and technical complaints related to central venous catheters marketed in Brazil.

Aim The objective of this study was to critically analyze data of the National Notification System for Adverse Events and Technical Complaints (Notivisa) related to central venous catheters, through an evaluation of the description of notifications recorded between 2006 and 2009. Methods Notifications were categorized and evaluated to: (i) determine the number of adverse events and technical complaints, (ii) verify compliance with the classification criteria defined by the legislation, (iii) reclassify notifications, when necessary, in order for them to fit in with the legal definitions, (iv) verify registered companies in Brazil, (v) quantify the notifications according to the registered company and product lot, and (vi) identify the country of original of the notified product. Microsoft Excel(r) 2010 was used to categorize and systematize the data. Results Some conceptual errors and incomplete records were found. Altogether, 228 notifications of technical complaints and 119 of adverse events were identified. Some notifications on guidewires and broken catheters were reported which led to the necessity of duplicating some medical procedures and to the occurrence of lesions/lacerations of vessels and tissue injury. Forty-seven percent of companies presented at least one notification in Notivisa and in all, 38 product lots had more than one notification. Conclusion These data support a necessity for cooperation between all entities of the National Health Surveillance System to check compliance of this type of product and to properly report adverse events and technical complaints. It is also important to incorporate minimum standards for the management of technologies in health services, including in the acquisition of products and training of staff.

DETERMINATION OF THE INFLUENCE OF BORATE ION ON THE DEGRADATION OF L-α-METHYLDOPA USING RP-HPLC WITH PHOTODIODE ARRAY DETECTION

The degradation of the drug L-α-methyldopa (MD) in alkaline solutions was studied by Reversed-Phase High Performance Liquid Chromatography. It was found that the presence of borate ion in the solution inhibited the formation of MD-melanin, the final product of degradation. It complexes with both MD and intermediates of the pathway, maintaining them longer in the medium. Through the use of a synthetic standard of a half-way intermediate of the oxidation pathway, 5,6-dihydroxy-2-methylindole (Me-DHI), and examination of the UV/vis spectra of the chromatographic peaks, it was possible to demonstrate the stabilization of a later stage degradation intermediate in the presence of borate ion. The inhibition of melanin formation may be correlated to the stabilization of this intermediate. Hence, this mechanism could be generalized and applied to biogenic catecholamines, such as dopamine and L-dopa, the natural precursor of mammalian melanin.

Perfil de queixas técnicas relacionadas a seringas hipodérmicas de uso único comercializadas no Brasil após certificação compulsória

Metrological certification is an important Sanitary Surveillance tool. The objective of this study was to evaluate the profile of notifications of technical complaints of hypodermic syringes performed in Notivisa/Anvisa (Sistema Nacional de Notificacoes de Eventos Adversos e Queixas Tecnicas/Agencia Nacional de Vigilância Sanitaria) between 2012 and 2015. The notifications were analyzed individually and classified according to the reasons reported. 4181 notifications were evaluated and the most prevalent complaints were: ‘broken product in the sealed package’ (22%) and ‘dirt/stains inside the product/packaging’ (15.8%). There were no significant changes in the profile of the complaints after compulsory certification, which, although indispensable, is not capable of replacing post-marketing monitoring.

SEPARATION OF DIFFERENT IONIC FORMS OF L-α-METHYLDOPA AND OTHER AMINO ACIDS BY REVERSED-PHASE ION-PAIR HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

The present work is devoted to the analysis of the phenomenon of “double peaks” of aminoacids in High Performance Liquid Chromatography. Therefore, we have carried out some experiments in order to confirm that the appearance of several peaks from the injection of a single compound was related to different ionic forms of this compound. It could be shown that elution of multiple peaks for L-α-methyldopa did not refer to its degradation products, but to the different ionic species present in the media. The same occurred with its derivative 3-O-methylmethyldopa and with dl-phenylalanine. The separation between ionic forms was possible due to the use of sodium heptanesulphonate, an anionic ion-pairing reagent, which selectively interacts with different charged species. These findings show that equilibrium species can be separated by an appropriate analytical method, depending on the employed conditions.