A disciplina de Pesquisa e Desenvolvimento de Medicamentos teve como objetivo geral expor o cenário e etapas da pesquisa e desenvolvimento de medicamentos, evidenciando estudos científicos, o desenvolvimento tecnológico, inovação, pré-formulação e caracterização de insumos farmacêuticos quanto aos aspectos de desenvolvimento de formas farmacêuticas sólidas. A disciplina também introduziu o cenário básico sobre pesquisa clínica de fármacos e medicamentos.

Após sua conclusão, o aluno se tornou apto a:

• Descrever as etapas mais importantes da cadeia de desenvolvimento de novos medicamentos.

• Reconhecer as diferenças entre medicamentos genéricos, similares e novos.

• Diferenciar insumo farmacêutico e forma farmacêutica.

• Organizar uma relação de informações importantes para um protocolo de desenvolvimento de uma formulação.

Abaixo, é possível encontrar algumas das atividades e avaliações desenvolvidas ao longo da disciplina.

A atividade final da disciplina consistiu na escolha de um tema inicialmente proposto pelo Professor Helvécio Rocha. O tema escolhido foi "Estrutura cristalina x biodisponibilidade". A partir disso, buscou-se um artigo que discorresse sobre o tema e, assim, selecionou-se o artigo "Bioavailability of indomethacin-saccharin cocrystals". A proposta do trabalho, o resumo do artigo selecionado e a apresentação crítica do mesmo encontram-se a seguir:

Bioavailability of indomethacin-saccharin cocrystals

Abstract

Objectives: Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee.

Methods: Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.

Key findings: The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P<0.05) than that of IND but not significantly different from Indomee (ANOVA, P>0.05).

Conclusions: The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.