Michele Georges Issa

Intrinsic Dissolution as a Tool for Evaluating Drug Solubility in Accordance with the Biopharmaceutics Classification System

The Biopharmaceutics Classification System (BCS) is a tool that was cr eated to categorize drugs into different groups according to their solubility and permeability characteristics. Through a combination of these factors and physiological parameters, it is possible to understand the absorption behavior of a drug in the gastrointestinal tract, thus contributing to cost and time reductions in drug development, as well as reducing exposure of human subjects during in vivo trials. Solubility is attained by determining the equilibrium under conditions of physiological pH, while different methods may be employed for evaluating permeability. On the other hand, the intrinsic dissolution rate (IDR), which is defined as the rate of dissolution of a pure substance under constant temperature, pH, and surface area conditions, among others, may present greater correlation to the in vivo dissolution dynamic than the solubility test. The purpose of this work is to discuss the intrinsic dissolution test as a tool for determining the solubility of drugs within the scope of the Biopharmaceutics Classification System (BCS).

The effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate of amlodipine besylate, using the rotating disk method

The aim of this study was to evaluate the effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate (IDR) of the antihypertensive drug amlodipine besylate, using the rotating disk method. Accordingly, a fractional factorial design (33-1) was used, employing dissolution media (water, phosphate buffer pH 6.8 and HCl 0.1 M), rotation speed (50, 75 and 100 rpm), and compaction pressure (1000, 1500 and 2000 psi) as independent variables. The assays were randomized and statistically compared using the Statistica(r) 11 software program. Significance testing (ANOVA) indicated that the dissolution medium had a considerable impact on the IDR of amlodipine besylate. Analysis of the linear and quadratic components of the variables led to the proposition of a mathematical model that describes the IDR as a function of the parameters studied. Conversely, the levels of compaction pressure and rotation speed employed during experimental planning were less relevant, especially when the assay was conducted in the HCl 0.1 M medium.

Physicochemical and dissolution profile characterization of pellets containing different binders obtained by the extrusion-spheronization process

Com a finalidade de se avaliar o comportamento de diferentes polimeros empregados como aglutinantes em pellets de pequeno diâmetro para uso oral foram preparadas formulacoes contendo paracetamol e um dos seguintes polimeros: PVP, PEG 1500, hidroxipropilmetilcelulose e metilcelulose por apresentarem diferentes propriedades aglutinantes. Os pellets foram obtidos pelo processo de extrusao/esferonizacao e secagem em leito fluidizado. Para avaliar a liberacao do farmaco, empregou-se o metodo 3 da Farmacopeia Americana, tambem conhecido como Bio-Dis e o metodo preconizado pela mesma farmacopeia para comprimidos de paracetamol. Os pellets foram avaliados, ainda, com relacao a granulometria, friabilidade, densidade verdadeira e teor. Os resultados indicaram que os diferentes aglutinantes empregados sao capazes de afetar a producao e algumas das caracteristicas fisico-quimicas dos pellets e o ensaio de dissolucao revelou que as formulacoes comportam-se como produtos de liberacao imediata. Os pellets obtidos apresentaram caracteristicas de liberacao favoraveis para a obtencao de comprimidos de liberacao instantânea. O aparato 3 da Farmacopeia Americana demonstrou ser um metodo com melhor capacidade discriminatoria entre as formulacoes, quando comparado com o metodo da cesta.

Applications of USP apparatus 3 in assessing the in vitro release of solid oral dosage forms

USP aparato 3 (cilindros reciprocos) e um equipamento bastante versatil para a avaliacao das caracteristicas de liberacao in vitro de formas farmaceuticas solidas orais, pois permite que o produto seja submetido a diferentes meios de dissolucao e condicoes de agitacao, em um unico ensaio. Neste trabalho, sao apresentados um breve historico e a descricao desse sistema, suas aplicacoes no desenvolvimento de produtos de liberacao imediata e modificada, assim como sua utilizacao na simulacao dos estados nao alimentado e alimentado com o emprego de meios biorrelevantes. Alem disso, uma comparacao e estabelecida com o cesto e a pa, com destaque para a hidrodinâmica superior do USP aparato 3, que faz com que os resultados nao sejam influenciados por fatores como o uso de sondas de coleta de amostras ou presenca de bolhas de ar no meio de dissolucao.

Development of a dissolution test method for enrofloxacin tablets using factorial design

Dissolution testing has emerged in the pharmaceutical field as a very important tool to characterise the performance of drug products. Enrofloxacin is an antimicrobial frequently used in veterinary medicine that has no dissolution method described in pharmacopoeias. In vitro dissolution tests of enrofloxacin tablets were performed using different test parameters under ‘sink’ conditions. A two-factor three-level factorial design was obtained using statistical software, on which nine runs were performed. The independent variables were rotation speed (50, 75 or 100 rpm) and dissolution medium (HCl 0.01 M, purified water or phosphate buffer pH 6.8). The response evaluated (dependent variable) was dissolution efficiency (%). The method using hydrochloric acid 0.01 M as the dissolution medium in USP Apparatus 2, with a rotation speed of 75 rpm proved to be the most appropriate. Under these conditions, this method was capable of distinguishing between different tablet formulations containing enrofloxacin.