Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

Abstract

Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally.

Figure 1

Evolution of pulmonary delivery devices

Figure 2

Lung deposition measured by several different investigators from a variety of dry powder inhalers (DPIs) vs. the specific resistance of the DPI. The increase in deposition seen with the higher resistance devices may, in part, be a function of the degree to which these DPIs de-aggregate the powder dose in the device at the start of the inhalation manoeuvre, thus providing a finer aerosol for inhalation. (Reproduced with permission from author [19].)

Figure 3

Comparison of the bronchoprotective effects of three doses of chlorofluorocarbon (CFC) and hydrofluoroalkane (HFA)-based salbutamol in patients with mild asthma. Dose–response curves of salbutamol plotted against PC₂₀ methacholine Proventil-HFA (▪) and Ventolin-CFC (○). (Reprinted with permission from author [61].)

Figure 4

Electron micrographs of a 2% albuterol sulphate–lactose powder blend. (a) Tomahawk-shaped lactose particle with drug on its surface. (b) The higher magnification shows individual drug particles (elongated crystals) on the lactose. (Reprinted with permission of author [72].)

Figure 5

Types of liposomes

Figure 6

Atomic force microscopy (AFM) images of free plasmid DNA, free cationic liposomes (using a cholesterol derivative) and their complexes. The complex formation induces the changes in the shape and size of the liposomes as shown in (c) and (d). (a) Free plasmid DNA with a circular DNA structure of 1.4 µm length. (b) Free small unilamellar vesicle (SUV) of cationic liposomes with a diameter of 200 nm. (c) Complex of DNA and liposome (with a cholesterol/phosphate ratio of 0.6) forms a necklace-like structure with the liposomes bound along the circular plasmid, and (d) the complex using a cationic liposome with a cholesterol/phosphate ratio of 1.2 forms large vesicles with a diameter of 1–1.5 µm where the DNA seems to be capsulated by a number of small cationic liposomes. (From: Nakanishi M, Noguchi A. Adv Drug Delivery Rev 2001; 52: 197–207 [86].)

Figure 7

Confocal microscopy images of large porous particles (pulmospheres). (A) Poly(lactic acid-co-glycolic acid) (PLGA) particle with diameter of 8.5 µm and density equal to 0.1 g cm⁻³. Double emulsion solvent evaporation techniques were used to prepare the highly porous particle. (B) Poly(lactic acid-co-lysine-graft-lysine) (PLAL-Lys) porous particles with diameter of 8.2 µm and density <0.1 g cm⁻³. (From: Edwards Da et al. Science 1997; 276: 1868–71 [95].)

Figure 7

Confocal microscopy images of large porous particles (pulmospheres). (A) Poly(lactic acid-co-glycolic acid) (PLGA) particle with diameter of 8.5 µm and density equal to 0.1 g cm⁻³. Double emulsion solvent evaporation techniques were used to prepare the highly porous particle. (B) Poly(lactic acid-co-lysine-graft-lysine) (PLAL-Lys) porous particles with diameter of 8.2 µm and density <0.1 g cm⁻³. (From: Edwards Da et al. Science 1997; 276: 1868–71 [95].)