Taste Masking of Bitter Drugs

• Autor(a) principal: Gomez, Susana Luísa Casegas de Carvalho
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/63363
• topic: taste masking; encapsulation efficiency; co-precipitation processes; dissolution; surface characterization techniques; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Taste masking of Active Pharmaceutical Ingredients (APIs) is critical in the development of solid oral dosage forms, since it is related to patient compliance, especially for pediatric populations. Therefore, it is essential to improve the existing methodologies and to develop new approaches that allow assessment of taste-masking efficacy. The current work focused on the production of taste-masked formulations of a bitter model drug substance and an appropriate excipient, using different co-precipitation processes: Stirred Reactor, Adaptive Focused Acoustics (AFA) technology and Microfluidization, for benchmarking purposes regarding taste masking properties. Thus, an experimental design of experiments was conducted to study the effect of different formulation variables (drug loading, feed solids concentration and solvent/antisolvent volume ratio) in the critical quality attributes of the spray-dried co-precipitated powders (drug’s solid state, morphology and particle size and dissolution performance). The encapsulation efficiency (EE) was then evaluated by using different dissolution methods and also surface characterization techniques (Scanning Electron Microscopy – Energy Dispersive X-ray Spectroscopy (SEM-EDS) and X-ray Photoelectron Spectroscopy (XPS)). Formulations were taste masked using any of the processes disclosed in this work. One of the formulations produced by Microfluidization technology, was the best regarding encapsulation efficiency, presenting a lower drug release in simulated salivary fluid within the first 5 minutes and the best encapsulation efficiency estimated by means of XPS. This can be explained by a high shear rate mixture provided by Microfluidization technology. Moreover, the pH shifts dissolution results for specific formulations and a commercial product (coated tablet) revealed similar dissolution profiles, meaning that the solubility of the drug substance (in the stomach and the upper intestine) seems not to be impacted by the processes used. According with the taste masking assessment techniques, EDS analysis presented some limitations and, in this case, it was proved not to be adequate, contrary to XPS which results corroborated the dissolution ones.