Dry Powder for Pulmonary Delivery: A Comprehensive Review

Abstract

The pulmonary route has long been used for drug administration for both local and systemic treatment. It possesses several advantages, which can be categorized into physiological, i.e., large surface area, thin epithelial membrane, highly vascularized, limited enzymatic activity, and patient convenience, i.e., non-invasive, self-administration over oral and systemic routes of drug administration. However, the formulation of dry powder for pulmonary delivery is often challenging due to restrictions on aerodynamic size and the lung’s lower tolerance capacity in comparison with an oral route of drug administration. Various physicochemical properties of dry powder play a major role in the aerosolization, deposition, and clearance along the respiratory tract. To prepare suitable particles with optimal physicochemical properties for inhalation, various manufacturing methods have been established. The most frequently used industrial methods are milling and spray-drying, while several other alternative methods such as spray-freeze-drying, supercritical fluid, non-wetting templates, inkjet-printing, thin-film freezing, and hot-melt extrusion methods are also utilized. The aim of this review is to provide an overview of the respiratory tract structure, particle deposition patterns, and possible drug-clearance mechanisms from the lungs. This review also includes the physicochemical properties of dry powder, various techniques used for the preparation of dry powders, and factors affecting the clinical efficacy, as well as various challenges that need to be addressed in the future.

A Pathway From Porous Particle Technology Toward Tailoring Aerogels for Pulmonary Drug Administration

“…Higher values are found in needle-shaped particles (χ = 1.7), however, the manufacturing of inhaled particles with needle-shaped particles poses a challenge on the industrial scale ( Moon et al, 2019 ). Despite that, fine particle fraction (FPF) obtained from plate-and needle-shaped particles are lower than those with spherical, pollen and cube-shaped particles ( Chaurasiya and Zhao, 2020 ).…”

“…These results were explained by the cohesive forces between particles resulting in agglomeration and low flowability performance of denser nonporous formulations. In contrast, inhaled particles with bulk density lower than 0.4 g/cm 3 can favor the aerosol penetration into the deep lung ( Chaurasiya and Zhao, 2020 ). In this favorable context of porous formulations for DPIs, aerogel particles are novel porous materials that consist in solid, lightweight and open porous networks of bonded particles or nanoscale fibers obtained from the removal of the fluid of a gel without significant structural modifications, so they maintain large surface areas and extremely low densities ( García-González et al, 2019 ).…”

Post-Processing Techniques for the Improvement of Liposome Stability

“…The presence of thin interstitial regions characterized by very small dendrite-shaped crystals results in a rapid reconstitution, the prevention of aggregation and improved stability in the freezing step of spray freeze drying [65,66]. The type of atomizer has been reported to be the most important factor that determines the particle size and size distribution of the final product [1,59]. Depending on the expected particle size, various nozzles have been utilized such as a hydraulic nozzle (120-250 µm in size) and a two/four-fluid pneumatic nozzle (5-100 µm in size).…”

“…Although the freeze drying process is suitable for preserving thermolabile substances, it is time consuming and, depending on the nature of the materials, the dry cake form of the final product can be very hygroscopic; hence, it may need to be kept in a specific container to prevent moisture sorption. To combine these advantages and compensate for the limitations of these methods, a spray freeze drying process was developed to provide dry products with a high stability [ 59 ]. The spray freeze drying process consists of three major steps: atomization, freezing and freeze drying [ 60 ].…”

“…As schematically illustrated in Figure 4 , atomization is the first step in the conversion of the prepared feed solution into spherical droplets through an atomizer. Subsequently, the freezing and freeze drying steps are performed to solidify the droplets using a cryogenic agent (or cold fluid) and sublimate the ice at a low temperature and pressure, respectively [ 59 ]. The physicochemical properties of the final product after spray freeze drying such as the particle size, particle morphology, density and porosity have been found to vary depending on the type of atomizer, freezing time and the composition and concentration of the feed solution.…”