Dissolution and Absorption of Inhaled Drug Particles in the Lungs

Abstract

Dry powder inhalation therapy has been effective in treating localized lung diseases such asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and lung infections. In vitro characterization of dry powder formulations includes the determination of physicochemical nature and aerosol performance of powder particles. The relationship between particle properties (size, shape, surface morphology, porosity, solid state nature, and surface hydrophobicity) and aerosol performance of an inhalable dry powder formulation has been well established. However, unlike oral formulations, there is no standard dissolution method for evaluating the dissolution behavior of the inhalable dry powder particles in the lungs. This review focuses on various dissolution systems and absorption models, which have been developed to evaluate dry powder formulations. It covers a summary of airway epithelium, hurdles to developing an in vitro dissolution method for the inhaled dry powder particles, fine particle dose collection methods, various in vitro dissolution testing methods developed for dry powder particles, and models commonly used to study absorption of inhaled drug.

Keywords: absorption; dissolution; dry powders; fine particle dose; inhalation.

Figure 1

Comparison of the tracheobronchial, bronchiolar and alveolar regions of the lungs [32]. Reproduced with permission from Ref. [32]. 2015, McGraw Hill.

Figure 2

Various approaches to collect fine particle dose (FPD). (A) Andersen Cascade Impactor (ACI), (B) Next Generation Impactor (NGI; top- closed view and bottom- open view of NGI), and (C) Twin Stage Impinger (TSI). Figures (A–C) were reproduced with permission from Driving Results in Inhaler Testing [Brochure, 2020 edition] [46], Copley Scientific Limited.

Figure 3

A modified Twin Stage Impinger (mTSI) to collect fine particle dose (FPD). Reproduced with permission from Eedara et al., 2019 [62], Springer Nature.

Figure 4

Schematic of paddle-over-disc apparatus with (A) membrane cassette, (B) NGI membrane holder. (A) reproduced with permission from Son and McConville 2009 [28], Elsevier. (B) reproduced with permission from Son et al., 2010 [50] Dissolution Technologies, Inc.

Figure 5

Schematic diagrams of (A) dialysis bag method, (B) flow-through cell [21], (C) Franz diffusion cell [27] and (D) Transwell^® system [20].. (B) reproduced with permission from Davies and Feddah 2003 [21], Elsevier. (C) reproduced with permission from Salama et al., 2008 [27], Elsevier. (D) reproduced with permission from Arora et al., 2010 [20], Springer Nature.

Figure 6

Schematic diagram of DissolvIt^® system. Reproduced with permission from Börjel et al., 2014 [59], Respiratory Drug Delivery 2014, Virginia Commonwealth University.