Dry-powder delivery

Developing an appropriate drug delivery system for a given drug can completely alter the drug s unfavorable properties, such as improve its effectiveness or reduce its side effects. Dry powder delivery systems such as microspheres are of special interest. In the last two decades they have been extensively studied with respect to nasal delivery and a considerable number of studies have been reported on that subject [3,23],... 

Potential solutions to these challenges to ensure effective inhalation drug treatment include active dry powder delivery systems, active liquid blister technology, and hydrofiuorocarbon (HFC) propellant nebulization systems. 

Pulmonary delivery of insulin for systemic absorption in the treatment of diabetes has been studied extensively since the early days of insulin discovery almost a century ago. Colthorpe et al. and Pillai et al. demonstrated in rabbit and monkey models, respectively, that the deeper into limg the dose of insulin was delivered, the higher was the bioavailability. The work of Laube, Benedict, and Dobs showed the need to achieve deep pulmonary deposition of this molecule for efficient absorption in humans. Handheld liquid and dry powder delivery systems have been developed to generate insulin-containing aerosols with the majority of the particles in the aerodynamic size range 1-3 pm. The relative bioavailability compared with subcutaneous injection based on the insulin contained in the dosage form was 110/ [52] powder system and for the aqueous-based... 

Figure 5 shows examples of two dry powder inhalers, the Turbuhaler and the Diskus, currently marketed in the United States for the delivery of the steroids, budesonide and fluticosone, respectively. Table 6 shows the major elements of a number of passive dry powder inhalers. In addition to the commercially available passive inhalation products, a number of active dispersion systems are under development the key characteristics of selected devices are shown in Table 7. 

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 degradation of proteins in the solid state occur to a lesser extent and typically via different mechanisms than those that occur in solution [109,110]. Lyophilization is currently the more common technique in the manufacture of dried therapeutic proteins however, there is increasing interest in the use of spraydrying, owing to the unique physical nature of the spray-dried powder and its potential usefulness in protein drug delivery. 

CFC, chlorofluorocarbon DPI, dry-powder inhaler HFA, hydrofluoroalkane MDI, metered-dose inhaler UK, unknown. °Lung delivery from in vivo radiolabel scintigraphy or pharmacokinetic studies. 

LiCalsi C, Christensen T, Bennett JV, Phillips E, Witham C (1999) Dry powder inhalation as a potential delivery method for vaccines. Vaccine 17 1796-1803. 

The DPI device presents medication to the patient as a dry powder in a form that can be inhaled orally for deliveiy to the target lung tissues. The delivery system should assist in the generation of very line particulates of medication in a way that enables them to avoid the impaction barriers that normally operate in the lung to prevent the ingress of potentially harmful particles. These barriers include the oropharynx and, for deep-lrmg delivery, the air-conducting bronchi and bronchioles. 

Studies have shown that in order to clear the oropharyngeal impaction barrier (comprising the mouth, throat, and pharynx), particles with aerodynamic diameters smaller than 5 pm are required [3,4]. Only particles with aerodynamic diameters less than 3 pm reach the terminal bronchi and the alveoli in significant numbers [5]. Therefore, the particle diameter required to be produced by the delivery system depends to a great extent on the intended target lung tissue. Lung deposition is also affected substantially by the specific inhalation dynamics of the patient, which in turn are influenced by the delivery device. This article addresses various attributes of the dry powder inhalation product, from intrinsic material properties to final product performance. 

TABLE 2 Energy Sources for Drug Delivery Inhalation, Dry Powder... 

This list is not exhaustive. Many other manufacturers, in both the United States and Europe, are developing dry powder inhalation drug-delivery systems. 

Schultz, R.K., Miller, N.C., Smith, D.K., and Ross, D.L.,J. Biopharm. Sci., 3 115-122 (1992). Hill, M., Characteristics of an Active Multiple Dose Dry Powder Inhaler, Proc. Respiratory Drug Delivery IV, Interpharm Press, Buffalo Grove, IL, 1994, pp. 109-116. 

Nebulizers and dry powder inhalers seem more appropriate systems to be used in the early stages of development of drug products for pulmonary drug delivery. However, it should not be concluded from this that the development of formulations for nebulizers or DPIs is easier and exhibits fewer theoretical and practical problems. 

Dry powder inhalers have initially found their application in inhalation therapy as a CFC-free alternative for the older MDIs. However, nowadays they seem to have a much larger potential [14,53], because of the high lung deposition that can be attained and also because they are suitable for the pulmonary delivery of therapeutic peptides and proteins [2,10,16]. 

The data in Table 8.2 are taken from a study reported by Hindle et the purpose of which was to determine whether a new dry powder inhaler (DISK) was equivalent to a traditional metered-dose inhaler (MDI) in its ability to deliver doses of a bronchodilator to the lungs of volunteers. The data are the percentages of an inhaled dose of salbutamol recovered in a urine sample taken 30 min post-inhalation for each method of delivery in nine volunteers. Ameasure of treatment effect is the difference in percentages within volunteers, shown in the fourth column. Of these differences seven are negative and two are positive (fifth column) and the question we need to answer is how likely is it that if there is no difference between the inhalers, we would see this degree of imbalance between negatives and positives ... 

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... 

Meakin BJ, Ganderton D, Panza I, Ventura P. The effect of flow rate on drug delivery from the Pulvinal, a high-resistance dry powder inhaler. J Aerosol Med 1998 ll(3) 143-52. 

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