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Benchmarking Supercritical CO₂-assisted Spray Drying with Conventional Spray Drying for the Manufacture of Inhalation Formulations

Temtem M, Moura C, Casimiro T, Costa E, Aguiar-Ricardo A.

RDD Europe 2017. Volume 1, 2017: 153-166.

Abstract:

Dry powder inhalation (DPI) formulations, where the API is embedded within a matrix of excipient(s), are gaining momentum. Spray drying (SD) is the most established technology in the pharmaceutical industry for manufacturing such composite particles. Spray drying is easily scalable, and enables fine control over particle properties, allowing optimal aerodynamic performance to be achieved via manipulation of formulation and process parameters. Other alternative technologies have meanwhile emerged based on the use of supercritical fluids, particularly supercritical CO₂ (scCO₂). Proposed industrial applications of scCO₂ have included its use as a solvent, antisolvent or adjuvant in processing, in fields such as particle engineering, sterilization and organic solvent-use minimization.

This paper reviews state-of-the-art applications of supercritical fluids in the successful preparation of inhalation powders, and offers a case study on the use of supercritical CO₂-assisted spray drying (SASD) technology benchmarked against conventional spray drying for preparation of a model composite particle formulation as presented in other publications where the composite particles are composed of trehalose and leucine. This work also seeks to optimize the process parameters of a supercritical CO₂-assisted spray drying process, and compare the results to what was achieved with an existing spray drying operation. A systematic quality by design (QbD) approach and a design of experiments (DoE) tool was utilized to develop statistical models to predict the fine particle fraction (FPF) of a powder for inhalation. The powders produced using the SASD apparatus exhibited a defined morphology, a narrow particle size distribution (PSD) and high FPF values, while maintaining a high process throughput and yield over the explored ranges. It was determined that SD and SASD at similar feed flowrate (F_feed) and inlet drying temperature (T_in) values enabled powders exhibiting similar FPF values, although the SASD particles seem to present a more homogeneous morphology, regardless of the process conditions. It was concluded that SASD has significant potential for processing some active pharmaceutical ingredients (APIs) for inhalation when the use of conventional technologies may be problematic. Such APIs include those exhibiting sensitivity to shear or thermal stress. SASD may also be able to generate low-bioburden formulation and products containing reduced levels of solvents.