Pulmonary Delivery of Drugs

In summary, inertial impaction is responsible for the deposition of the larger airborne particles and this occurs mainly in the upper airways. In practice, therefore, we find that only those particles smaller than about 10 pm will travel beyond the main bronchi. Such particles have a decreasing propensity to be deposited by inertial impaction the further they travel into the lungs, but are more likely to be deposited by the action of sedimentation and diffusion as they reach the smaller airways and the alveolar region, where air velocities are low, airway dimensions are small and air residence times are relatively high. 

---

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

Patton JS Pulmonary delivery of drugs for bone disorders, Adv Drug Deliv Rev 2000,... 

For pulmonary delivery of drugs, what size range of particles is desirable and why ... 

A Adjei, J Garren. Pulmonary delivery of peptide drugs effect of particle size on bioavailability of... 

J. S. Patton and R. M. Platz, Routes of drug delivery case studies (2) pulmonary delivery of peptides and proteins for systemic action, Adv. Drug Deliv. Rev, 8, 179 (1992). 

Klyashchitsky, B. A., Owen, A. J., Nebulizer-compatible liquid formulations for aerosol pulmonary delivery of hydrophobic drugs glucocorticoids and cyclosporine,... 

Taljanski W, Pierzynowski SG, Lundin PD, Westrom BR, Eirefelt S, Podlesny J, Dahlback M, Siwinska Golebiowska H, Karlsson BW (1997) Pulmonary delivery of intratracheally instilled and aerosolized cyclosporine A to young and adult rats. Drug Metab Dispos 25 917-920. 

One of the main drivers for the development of new pulmonary drug delivery systems has been the potential for noninvasive systemic delivery of protein and peptide compounds. The systemic delivery of macromolecules via the airways would overcome the inconvenience and cost associated with current methods of administration (injection), and appears likely given the large surface area of the airways and the thin pulmonary epithelium. Most research has concentrated on pulmonary delivery of insulin for the treatment of diabetes. Recently, one insulin product has completed phase three studies and is now undergoing review by European regulatory agencies for marketing approval. 

Inhalation aerosols have been used for the delivery of drugs to the respiratory system since the mid-1950s. The most common dosage form for inhalation is the metered-dose inhaler (MDI), by which the drug is delivered from a pressurized container using a liquefied gas propellant. Medication delivered via this dosage form has allowed for a quick therapeutic response to the symptoms of asthma, emphysema, and chronic obstructive pulmonary disease (COPD), and has resulted in an improvement in the quality of life for millions of asthma sufferers. 

Powder injection applies many of the principles of pulmonary delivery of dry powders to the lungs The drug has to be in the form of very small particles, is dispensed from a reservoir, and is delivered as an aerosol i.e., particles are dispersed in a gas. Liquid or dissolved drug can be delivered by precipitation or adsorption onto carrier particles. The big difference with pulmonary delivery is the momentum at which the particles are delivered. Driven by a high-pressure helium gas stream, the particles travel fast enough to penetrate the outer layer of the skin, the stratum corneum. The design of devices to deliver needle-free injection of solids was pioneered by researchers at the University of Oxford who founded PowderJect Pharmaceuticals PLC in 1993 (now PowderMed Ltd.) to develop the only powder-based technology so far. Since that... 

B. E. Gilbert, and V. Knight, Pulmonary delivery of antiviral drugs in liposome aerosols, Semin. Pediatr. Infer. Dis. 7 148 (1996). 

R. J. Gonzalez-Rothi, and H. Schreier, Pulmonary delivery of liposome encapsulated drugs in asthma therapy, Clin. Immunother. 4 331 (1995). 

Several pharmaceutical and physiological barriers must be overcome for the successful pulmonary delivery of peptide and protein drugs [3], For example, many of these macromolecular drugs have relatively low permeability when they are administered without any absorption enhancers [4], Furthermore, the clinical toxicology of peptides/proteins in the lung, especially for chronic disease, should be of some concern [6], Therefore, cost-benefit ratios should be evaluated in the... 

Adjei, A., and J. Garren. 1990. Pulmonary delivery of peptide drugs effect of particle size on bioavailability ofleupro-lide acetate in healthy male volunteers. Pharm. Res. 7 565-569. 

Kawashima, Y. (1995). Aerosolization oflactide/glycolide copolymer (PLGA) nanospheres for pulmonary delivery of peptide-drugs. Yakugaku Zasshi 115, 732-741. 

---