Aerosol delivery inhalations

Ben-Jebria A, Eskew ML, Edwards DA (2000) Inhalation systems for pulmonary aerosol delivery in rodents using large porous particles. Aerosol Sci Technol 32 421-433. 

Dahlback M, Eirefelt S, Nerbrink O (1996) Aerosol delivery to the respiratory tract in experimental animals. In Marijnissen JCM, Gradon L (eds.) Aerosol Inhalation Recent Research Frontiers. Kluwer academic publishers, Netherlands, pp 235-246. 

Aerosolized medications are available as pressurized or breath-actuated metered-dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulized or wet aerosols. Most inhaled medications currently used are available as metered-dose inhalers (Table 3). For the patient who has difficulty to coordinate activation of a MDI, a spacer improves delivery. Spacers reduce deposition of the drug in the... 

Depending on the particle morphology, several administration methods can be used aerosol, inhalation, and systemic- and subcutaneous injections. Typically, particles in the range of 5 to 100 pm are subcutaneously injectable, 1-5 pm particles are suitable for aerosol delivery and... 

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. 

During normal nose breathing the majority of inhaled environmental particles are deposited in the nose and pharynx, as described in Chapter 9 (Section 9.2). Hence for pulmonary drug delivery, the aerosols are inhaled via the mouth. 

Akwete, A.L., Gupta, P.K., Eds. Niven, delivery of biotherapeutics by inhalation aerosol. In Inhalation Delivery of Therapeutic Peptides and Proteins, Marcel Dekker, Inc. New York, 1997 151-231. 

Metered dose inhaler has been the most popular aerosol delivery device for the treatment of respiratory diseases, which is attributable to its portability and simple operation. Although seemingly easy to use, the MDI is a sophisticated device in design. The drug(s) are suspended or dissolved in a liquefied propellant system, which may also contain excipients such as cosolvents or surfactants. The formulation is kept pressurized in a small canister, sealed with a metering valve. Upon actuation through an actuator, the valve opens and the metered dose is dispensed as an aerosol spray from the expansion and vaporization of the propellant under ambient pressure. The inhalers may be used alone or with spacer devices, the electrostatic issues of which are considered in a later section. The present discussion focuses on the inherent charging of particles produced from MDIs. 

Duration of aerosol dose generation should occupy a substantial part of a slow inhalation cycle. A generation time of greater than 1 s will permit the patient to better coordinate aerosol delivery effectively during inhalation. 

Volume inhaled at the time of actuation of aerosol delivery... 

Derksen F, Olszewski M, Robinson N 1996 Use of a handheld, metered-dose aerosol delivery device to administer pirbuterol acetate to horses with heaves. Equine Veterinary Journal 28 306-310 Derksen F, Olszewski M, Robinson N 1999 Aerosolized albuterol sulfate used as a bronchodilator in horses with recurrent ainway obstruction. American Journal of Veterinary Research 60 689-693 Duvivier D, Votion D, Vandenput S et al 1997 Technical validation of a facemask adapted for dry powder inhalation in the equine species. Equine Veterinary Journal 29 471-476... 

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. 

Dolovich M. Aerosol delivery devices and airways/lung deposition. In Schleimer R, O Byrne P, Szefler SJ, Brattsand R, eds. Inhaled Steroids in Asthma Optimizing Effects in the Airways. New York Marcel Dekker, 2002 169-211. 

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... 

Enantiomer Preparations of Inhaled Drugs. There has been much interest in the differences in effects of enantiomers of many medications, and beta agonist adrenergic bronchodilators have received much attention. Evidence suggests that the (R)-enantiomer of albuterol is mainly responsible for bronchodilation while the (S)-enantiomer may stimulate airway reactivity. Data suggest, however, that after aerosol delivery, the systemic absorption for (R)-albuterol is faster than for (S)-albuterol and that, conversely, the lung retention of (S)-albuterol is longer, which may be detrimental [29]. The extent to which enantiomers will displace racemic preparations is not yet determined. 

N-Acetylcysteine. Mucolytic agents such as IV-acetylcysteine (NAC) have been used by aerosol delivery in an attempt to aid in sputum clearance. Supplied in sufficient quantity, acetylcysteine will help liquefy tenacious secretions and make their clearance easier. A review of studies on the use of NAC in CF concluded the evidence does not support its use, either via nebulizer or by mouth [93]. Intravenous NAC was tested and found not useful in acute respiratory distress syndrome [94]. In one study, patients with chronic bronchitis who took oral NAC had fewer exacerbations and better symptom improvement than did control patients [95], In the United States, there is no use of NAC by any route for chronic bronchitis. These data need more examination and further study before any such use might be considered. A newer mucolytic agent, nacystelyn, has been developed for delivery via a dry powder inhaler. Deposition in adults and children with CF was 16% and 23%, respectively [94]. 

Surfactant aerosol also has been tested in chronic bronchitis the modest improvement in FEV1 was small, and its expense would not justify use based on these data [175]. In tests of aerosol surfactant in adults with CF treated over 5 days, no improvement was found [176]. Although instilled surfactant has become common practice for the neonatal respiratory distress of premature infants, aerosol delivery is not yet adequately developed. A recent study showed no difference in outcome for spontaneously breathing newborns who inhaled either surfactant or placebo via a CPAP mask [177]. There continues to be great appeal for the use of surfactant in adults because of the apparent success in neonates, but its use should not become practice until well-controlled trials document clinically meaningful efficacy. 

Better education of physicians and clinic/hospital staff is necessary if the new methods for aerosol delivery are to be brought to the patient. Good patient education is a time-consuming but necessary final part of the application of inhaled medications to the therapeutic armamentarium. These efforts should allow the clinician to bring to the patient the best evidence-based management, which will really change performance and lengthen life. 

Dolovich MB, Ruffin RE, Corr D, Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device. Chest 1983, 84, 36-41. 

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