ABSTRACT Fibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis. Three drugs in the fibrate class, ciprofibrate, fenofibrate and bezafibrate, were chosen for this study because their raw materials are readily available and because scientific publications on these compounds is limited. To evaluate their intrinsic stability, the drugs were exposed to a test condition (temperature, oxidation, UV light exposure, hydrolysis at different pH values and metal ions in solution) and then were subjected to analysis by HPLC. The samples were run on a C18 column, with a flow rate of 1.0 mL min-1 in a mobile phase consisting of methanol: 0.01 % phosphoric acid v/v (80:20), with variable detection wavelengths in the UV spectra. The analysis methodology showed satisfactory performance parameters. The three drugs were very unstable, degrading in each of the conditions evaluated. The test conditions of acid and basic hydrolysis showed the most significant degradation. The results demonstrated that the drugs in this class are unstable. Based on these experimentally determined degradation kinetics, it is easy to understand and emphasize the importance of the lack of liquid dosage forms on the market for fibrates because of their instability.

Atorvastatina (ATV) é um fármaco antilipêmico de grande interesse para a indústria farmacêutica. ATV não apresenta monografia na Farmacopéia Brasileira e metodologias analíticas para sua determinação foram validadas. As condições cromatográficas utilizadas foram: coluna RP-18-octadecilsilano (250 x 4.6 mm, 5 mm), detecção em 238 nm, fase móvel contendo ácido fosfórico 0,1% e acetonitrila (35:65% v/v), fluxo de 1,5 mL min-1, temperatura do forno de 30 ºC e volume de injeção de 10 mL. ATV é classificada como um fármaco de classe II, de acordo com o sistema de classificação biofarmacêutica (SCB). Como tal, um teste de dissolução foi proposto para avaliar as formulações farmacêuticas do mercado atual, sob as seguintes condições: água como meio de dissolução, volume de 1000 mL, aparato pá, velocidade de rotação de 50 rpm, 80% (Q) em 15 minutos com leituras espectrofotômetro UV a 238 nm. Na condição padrão proposta para o teste de dissolução, o qual seria capaz de diferenciar apropriadamente as formulações farmacêuticas, o produto genérico não foi considerado equivalente farmacêutico. No entanto, em outros métodos de dissolução menos discriminativos, que também seriam considerados apropriados pelos parâmetros legais, este produto pode vir a ser considerado como genérico.

Atorvastatin (ATV) is an antilipemic drug of great interest to the pharmaceutical industry. ATV does not appear in the monographs of Brazilian pharmacopoeia, and analytical methodologies for its determination have been validated. The chromatographic conditions used included: RP-18 column-octadecylsilane (250 x 4.6 mm, 5 mm), detection at 238 nm, mobile phase containing 0.1% phosphoric acid and acetonitrile (35:65% v/v), flow at 1.5 mL min-1, oven temperature at 30ºC, and injection volume of 10 mL. ATV is classified as a class II product, according to the biopharmaceutical classification system. As such, a dissolution test was proposed to evaluate pharmaceutical formulations on the market today, under the following conditions: water as a dissolution medium, 1000 mL as a volume, paddle apparatus at a rotation speed of 50 rpm, 80% (Q) in 15 minutes with UV spectrophotometer readings at 238 nm. In the pattern condition proposed as the ideal dissolution test, which appropriately differentiates amongst formulations, the generic product was not considered pharmaceutically equivalent; however, in other less differential dissolution methods, which also fall within appropriate legal parameters, this product could come to be regarded as generic.

Several matters of the pharmaceutical demonstrate the great importance of thermal analysis application, especially TG and DSC for the pharmaceutical industry future, namely: characterization of the drugs with the thermal events definition, in studies of drug purity, in the polymorphs identification, in compatibility studies of solid dosage pharmaceutical formulations, in drugs and pharmaceutical formulations thermal stability, and in determination of shelf life for isothermal degradation kinetics by extrapolation using the Arrhenius equation. Thus, the test results obtained from thermal analysis are directly related to the quality of a pharmaceutical product, whether the stability or bioavailability of the pharmaceutical product.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for drugs characterization, purity, formulations compatibility, polymorphism identification, stability evaluation, and thermal decomposition of drugs and pharmaceutical formulations. Simvastatin showed fusion at 138.5 ºC and thermal stability up to 248 ºC. Simvastatin was incompatible with preservative excipient butylhydroxyanisole (BHA) performing a process of crystal amorphization. The drug showed morphological polymorphism, where it has the same unit cell but with different crystal habits according to the recrystallization solvent.