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.
Highlights
Lungs are bifurcated into the right and left lung; the right lung is further divided into three lobes, while the left lung is divided into two lobes
We have summarized the roles of the architecture of pulmonary airways and the physicochemical properties of dry powders in aerosolization, inhalation, deposition, and clearance
The pulmonary route has been used for drug delivery since ancient times due to its many advantages over other routes of drug administration
Summary
Lungs are bifurcated into the right and left lung; the right lung is further divided into three lobes, while the left lung is divided into two lobes. Several approaches have been used to overcome these obstacles and improve the bioavailability of administered drugs This includes manipulation of particle morphology (size and shape) for optimal inhalation, coating of the exterior surface of respirable particles with pulmonary-compatible materials [9], maximal deposition, and efficient escape from macrophage recognition [10]. The most common technique for optimizing the physicochemical properties of dry powder to enhance inhalation is mechanical milling [15] This technique is simple and economical but has various technical problems like inconsistent morphology, thermodynamically activated surfaces, and high electrostatic charges of the particles arising from high share impaction forces during production [16,17]. We have described various techniques for the preparation of dry powder for inhalation, factors affecting the clinical efficacy, and various challenges related to dry powder preparation for inhalation
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