Aerosol delivery systems

Johnson, M., Fluticasone Propionate Pharmaeokinetic and Pharmaeodynamie Implieations of Different Aerosol Delivery Systems. Proc. Respiratory Drug Delivery VI, Interpharm Press, Buffalo grove, IL, 1998, pp. 61-70. 

Everard, M.L., Stammers, J., Elardy, J.G., and Milner, A.D., New aerosol delivery system from neonatal ventilator circuits, Dis. Childhood, 67 826-830 (1992). 

Of 335 patients with type 1 diabetes randomized to receive preprandial inhaled insulin as a dry powder formulation via an aerosol delivery system (Exubera) plus bedtime subcutaneous Ultralente insulin, or to continue NPH and regular insulins subcutaneously, 170 received inhaled insulin (mean age 33 years) (272). Six discontinued inhaled insulin, one because of mild cough, two because of hypoglycemia, and three because of insufficient responses. The risk of hypoglycemia was slightly lower in those who used inhaled insulin, at 8.6 events per month compared with 9.0 events per month in the conventional insulin group. 

Figure 1 Typical metered-dose aerosol delivery system.

M. E. Ward, A. Woodhouse, L. E. Mather, S. J. Farr, J. K. Okikawa, P. Lloyd, J. A. Schuster, and R. M. Rubsamen, Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system, Clin. Pharmacol Ther 62 596 (1997). 

Later, Lizio et al. [78] used a new aerosol delivery system (ASTA-ADS) to investigate the pulmonary absorption and tolerability of four different cetrorelix formulations delivered as nebulized aerosols to orotracheally cannulated rats. After only 5 min exposure to the cetrorelix aerosol, serum testosterone concentrations were reduced to subnormal levels over a 24-h period. After dose adjustment (dose delivered minus exhaled amount), the bioavailabilities for pulmonary delivery ranged from 48.4 27.0% to 77.4 44.0% compared to IV administration. In addition, the lung function parameters did not reveal any formulation-related changes. Overall, the results of cetrorelix aerosol administration compared well with those obtained with intratracheal instillation of cetrorelix solution [77]. 

G. Borchard, and C.M. Lehr. 2001. Systemic delivery of cetrorelix to rats by a new aerosol delivery system. Pharm. Res. 18 771-779. 

Smyth, H. D., and Leach, C. L. (2005), Alternative propellant aerosol delivery systems, Crit. Rev. Ther. Drug Carrier Syst., 22, 493-534. 

Figure 7.11. Photo of a glass aerosol delivery system used to spray solvent-suspended particulates onto a TEM grid.

For the systemic delivery of most drugs, however, currently marketed aerosol delivery systems are inadequate due to the following ... 

One of the oldest medical aerosol delivery systems is the air jet nebulizer, which forms a fine mist of liquid droplets from a drug solution that a patient breathes over a period of 10-30 min/dose. The cumbersome... 

Schuster, J.A. Farr, S.J. Cipolla, D. Wilnbanks, T. Resell, J. Lloyd, P. Gonda, I. Design and performance validation of a highly efficient and reproducible compact aerosol delivery system AERx . In Respiratory Drug Delivery VI Dalby, R.N., Byron, P.R., Farr, S.J., Eds. Interpharm Press, 1998 83-90. 

Schuster, J. Rubsamen, R.M. Lloyd, P. Lloyd, J. The AERx Aerosol Delivery System. Pharma. Res. 1997,... 

Cipolla, D.C. Clark, A.R. Chan, H.-K. Gonda, I. Shire, 59. S.J. Assessment of aerosol delivery systems for the recombinant human deoxyribonuclease I (rhDNase). STP Pharma Sciences 1994, 4, 50-62. 

The Bespak Piezo Electric Actuator is a novel aerosol delivery system based on a piezoelectric crystal combined with an electroformed mesh (Fig. 3). It produces droplets of adjustable size from a single metered drop or fluid reservoir. The mesh hole dimension (as small as 3 pm) determines the size of the droplets produced, whereas the size and density of the holes control the rate of fluid delivery. These can be varied according to the formulation. Although solutions are more readily nebulized, suspensions can be aerosolized if the particle size of the suspended particles is two to three times smaller than the mesh size. 

Varner A, Busse W 1996 Are you undertreating inflammation in asthma Journal of Respiratory Disease 17 656-668 Viel L 1999 Therapeutic efficacy of inhaled fluticasone propionate in horses with chronic obstructive pulmonary disease. In Proceedings of the 45th American Association of Equine Practitioners Annual Convention, Albuquerque, NM, pp. 306-307 Votion D, Ghafir Y, Munsters K et al 1997 Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery system. 

The patient factors enter into play in several ways. The effectiveness of all aerosol delivery systems depends to some extent on the ability of the patients to use them properly. This has been shown for different types of inhalation systems, such as metered-dose inhalers [28,29] and the breath-driven powder generators [15,30]. The second determinant is the state of the patient s airways. These effects are discussed in greater detail in the following section. 

Figure 6 Different inlets used to couple a cascade impactor to an aerosol delivery system. The inlets range in volume from 66 to 1080mL [92] and collect varying amounts of drug, depending on their volume. This in turn affects the amount of aerosol sampled by the impactor.

The use of aerosol delivery systems continues to be a desirable means of administering locally acting agents to the lungs. Since the early 1990s there has been a surge of interest in the pulmonary delivery of proteins and peptides for systemic activity but to date none of these products have made it to market [1], During this period the major commercial successes have been in the form of dry powder systems [2] and alternative propellant systems [1], as will be discussed later in the chapter. The incidence of asthma and chronic obstructive disease continues to rise and the need for improvement and diversity of therapies remains a priority in their treatment [3]. 

Most aerosol delivery systems have surfaces that are designed to collect or disperse particles. Jet nebulizers have spheres, as shown in Fig. 4, or plates placed immediately in front of the jet to collector break up large droplets. Metered-dose inhalers do not traditionally have baffles however, the surface of the actuator collects aerosol particles as they pass through the mouthpiece. Dry powder... 

The potential benefit of aerosolized antibiotic therapy is dependent on three factors characteristics of the disease, aerosol delivery system, and properties of the antimicrobial agent [5]. Diseases that are likely to respond better cause infection in the airway without significant parenchymal or systemic involvement (e.g., cystic fibrosis). There is a significant need for research and scientific advances in the area of aerosol delivery of these therapies. Delivery systems that produce reliable, consistent, and reproducible aerosols are essential. Formulation of drug products requires attention to integrity, stability, tolerability, and overall suitability for aerosolization. 

Farr S. AERx development of a novel liquid aerosol delivery system concept to clinic. In Respiratory Dmg Delivery V Dalby RN, Byron PR, Farr SJ, eds. Interpharm Press Phoenix AZ, 1996 175-185. 

In the following sections, the performance of recently developed devices will be contrasted with that of earlier systems in order to emphasize the progress that has been made. The Conclusion will focus on reasonable expectations for the future and indicate areas in which further fundamental observations may facilitate the design and production of new aerosol delivery systems. 

Urine (Matusiewicz and Barnes, 1985) - NIOSH-NBS freeze dried urine is reconstituted in water. 50 nL samples are determined. Instrumentation Plasma-Therm model 5000D ICP-AES spectrometer. Instrumentation Laboratory FASTAC II pneumatic nebulizer/aerosol delivery system to deliver sample to a model IL655 furnace for graphite furnace vaporization at 2500°C. Argon plasma, 40.68 MHz, A = 231.60 nm, pyrolytically coated graphite tube with platform. Detection limit 0.9 hqIL (45 pg Ni) by peak area, 12 /peak height. Urine reference material found 1.05 mg/L (RSD 2.1%), expected 1.01 0.11 mg/L. 

The only U.S. FDA-approved DNase product, Dornase alpha (inhalation solution), has been developed as a therapeutic agent for the management of CF. The product is supplied in single-use ampules delivering 2.5 ml of a sterile, clear, colorless solution containing 1.0 mg/ml of dornase alpha with no preservative. Administration is by nebulizer aerosol delivery systems. 

Marple V, Olson BA, Miller NC. The role of inertial particle collectors in evaluating pharmaceutical aerosol delivery systems. J Aerosol Med 1998 11(1) S139-S153. 

Everard ML. Assessment of aerosol delivery systems. Pediatr Pulmonol 1997 16 186-187. 

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