Screening and Optimization of Formulation and Process Parameters for the Manufacture of Inhalable Composite Particles by Spray-drying

Cláudia Moura, João Vicente, Maria Palha, Filipe Neves, Ana Aguiar-Ricardo, Eunice Costa

Drugs for dry powder inhaler systems are conventionally formulated using a carrier-based approach. However, due to blend uniformity issues and poor drug delivery efficiency frequently observed with this formulation strategy, integrated particle engineering and formulation approaches are being explored.
The current work addresses the use of spray drying (SD) to produce composite particles with improved aerodynamic performance (AP), focusing on the screening and optimization of formulation composition and operating conditions. All powders were SD using a BUCHI model B-290. During the screening phase, a Design of Experiments (DoE) was performed using several excipients, sugars and amino acids, previously used in inhalation formulations. Based on particle size and scanning electron microscopy morphology data, yield and AP, the system composed of trehalose and leucine was selected for optimization. The optimization phase consisted on a second DoE to study the influence of SD process parameters on the AP. As in the previous phase, this was assessed by an Andersen cascade impactor using a Plastiape HR model 7 at 60 L/min.
Overall, it was demonstrated that the integrated optimization of composition and process conditions can enable high drug delivery efficiency, with fine particle fraction values of 70% achieved by careful selection of feed concentration, atomization gas flow and solvent system. Most importantly, the results obtained in this work suggest that for low-dosage formulations, development of composite particle systems can be performed independently of the Active Pharmaceutical Ingredient (API), as the incorporation of 1% w/w of API showed negligible impact on the physical attributes and resulting performance of these particles.

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