Manipulation of Spray-dried Composite Particles Physiochemical Properties and In-vitro Performance

Cláudia Moura, Susana Campos, Filipe Neves, Ana Aguiar-Ricardo, Eunice Costa

Drugs for dry powder inhaler (DPI) systems are conventionally formulated using a carrier-based approach. However, drawbacks such as poor drug delivery uniformity and efficiency are frequently observed. To overcome these constrains, new particle engineering technologies that enable the manipulation of formulation/process parameters are being explored, namely, the production of carrier-free composite particles using spray-drying (SD) technology.
The current work addresses the use of SD to produce composite particles of trehalose and L-leucine with improved aerodynamic performance that are suitable for APIs with low and high water solubility, by focusing on fine-tuning the formulation composition and operating conditions. The experiments were conducted based on Quality-by-Design (QbD) principles. All powders were SD according to a Design of Experiments (DoE) in which the formulation: L-Leucine and ethanol percentages, as well as the process outlet drying temperature were manipulated. The impact of the formulation/process variables on the powder properties (particle size, morphology, bulk density, water content) and aerodynamic performance (emitted mass, fine particle fraction (FPF<4.4μm)) were evaluated and quantified. A statistical model was further implemented to predict the FPF of the resulting powders.
Overall, it was demonstrated that the integrated optimization of composition/process conditions can improve the drug delivery efficiency, reaching FPF values of ~70% (relatively to the capsule fill weight). It was observed that the ethanol percentage and the outlet temperature were the main contributors for the FPF manipulation, where a direct correlation with the FPF improvement was observed. The leucine percentage had a negligible impact on the powder FPF. The FPF was successfully predicted by a statistical model.

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