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Evaluation of the mechanical properties of powder particles intended for inhalation
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Orientador(es)
Resumo(s)
Pulmonary drug administration has been the subject of investigation due to its advantages such as the avoidance of the first pass effect, rapid onset of action and small drug doses.
Carrier-based dry powder inhalers (DPI) are, as the name indicates, dry powder formulations of inhaled medications. In these, the micronized active pharmaceutical ingredient (API) is blended with coarser excipient particles, the carrier, to provide better bulk properties, flowability and achieve reproducible dosing. However, the production of DPI products is quite complex and to obtain stable formulations, particle properties of the API, excipients and their respective mixtures are important factors to consider. The aim of this work was to understand how the mechanical properties of distinct powder particles intended for inhalation, influence the powder bulk properties and, consequently, their influence in the in vitro aerodynamic performance of DPIs. For this, jet-milled Salbutamol Sulphate (SS) was selected as a model API and four different grades of lactose (Duralac H, Flowlac 90, Respitose SV003 and Lactohale 100) were chosen as potential carriers. Adhesive blends of API (2%) and excipients were produced. Particle size distribution (PSD), hardness, porosity and flowability of the powders and blends were studied. It was found that the API increased the values of tensile strength of pure lactoses due to a decrease in porosity. Also, it was demonstrated that cohesivity and compressibility of the powder bed of the raw materials and blends increased with the presence of a higher percentage of fine particles. However, the latter turned the powders less permeable to air. Finally, the aerodynamic performance of the adhesive blends was tested using a Next Generation Impactor (NGI), at two different flow-rates: 60 and 100 L/min. It turned out that a higher flow-rate resulted in a higher fine particle fraction (FPF) values for all the blends. The best performance was achieved with SS+Duralac H, being unresponsive to different flowrates and having the highest and constant values of FPF.
Descrição
Tese de mestrado, Engenharia Farmacêutica, Universidade de Lisboa, Faculdade de Farmácia, 2018
Palavras-chave
Adhesive mixtures Carrier Dry powder inhalers (DPIs) Lactose Salbutamol sulphate Teses de mestrado - 2018