Powder aerosol delivery

This review captures some of the most recent technologies with examples relating to pharmaceutical dry powder aerosol delivery. 

Dry-powder aerosol delivery offers yet another set of challenges from an in vitro/in vivo correlation perspective. There are two main types of dry-powder inhaler those that are passive and rely on the patient s inspiratory effort to generate the aerosol and those that are active and use some form of internal power source. Examples of the former would be the Turbuhaler, Accuhaler/Diskus, and the Uke. Examples of the latter are the Dura Spiros and the Inhale pulmonary delivery system. Characterizing the aerosol clouds generated by these devices in a manner usefiil for deposition predictions can require different experimental approaches. 

NM Concessio, MM Van Oort, M Knowles, AJ Hickey. Pharmaceutical dry powder aerosols correlation of powder properties with dose delivery and implications for pharmacodynamic effect. Pharm Res 16 833-839, 1999. 

The DustGun aerosol generator, which has been reported for the delivery of aerosol particles to the IPL for toxicological evaluations [36], is another delivery technique which could be utilised for the evaluation of drug disposition after the delivery of pharmaceutical powder aerosols to the IPL. 

Lucas P, Clarke MJ, Anderson K, Tobyn MJ, Staniforth JN. The role of fine particle excipients in pharmaceutical dry powder aerosols. Paper presented at Respiratory Drug Delivery VI, 1998. 

Smyth HDC, Garmise RJ, Cooney DJ, Zimmerer RO, Pipkin JD, Hickey AJ. Influence of physical form of Captisol particles on performance as a dry powder aerosol carrier. Paper presented at Respiratory Drug Delivery IX, Palm Desert, California, 2004. 

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. 

Aerosol delivery of the precursors was chosen because it was expected that although the species were monomeric, their volatility was likely to be low based on the TGA results described earlier, and that the crown ether might dissociate on heating for extended periods. The compound Ca(SOCMe)2(15-crown-5) was dissolved in ethanol and delivered in a nitrogen gas stream to a cold-wall atmospheric pressure CVD reactor where the substrate temperature was varied between 300 and 400°C. Analysis of films deposited at 310°C revealed that crystalline CaS was deposited, approximately 100 nm thick, with a deposition rate of 10 nm/min. The X-ray powder pattern indicates that CaS was formed with preferential (200) orientation (see Fig. 63). The SEM data showed that the films comprised cubic crystallites with dimensions consistent with the linewidth of the peaks observed by X-ray diffraction. The bulk composition corresponded to CaS as determined by AES. 

Chan, H.-K. Clark, A. Gonda, I. Mumenthaler, M. Hsu, C. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm. Res. 1997, 14, 431-497. 

Vanbever, R. Optimization of dry powder aerosols for systemic drug delivery. In Optimization of aerosol drug delivery Gradon, L., Marijnissen, J., Eds. Kluwer Academic Publishers Dordrecht, 2003 91-103. 

Fiegel J, Fu H, Hanes J. Poly (ether-anhydride) dry powder aerosols for sustained drug delivery in the lungs. / Control Release 2004 96(3) 411-123. 

Shama JO-H, Zhang Y, Finlay WH, Roa WH, Lobenberg R. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm... 

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... 

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. 

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... 

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]. 

Staniforth JN. Pre-formulation aspects of dry powder aerosols. Respir Drug Delivery V 1996 ... 

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