Powder inhalers

Although a number of patents for powder delivery devices for medicinal purposes were filed from the middle of the twentieth century, the first widely used powder inhaled was sodium cromoglycate. 

In the mid-1950s, Khellin analogues were being investigated as potential 

Marcel Dekker, Inc. 270 Madison Avenue, New York, New York 10016 

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Formulation(s) cps. for inhalation 12 jig (as fumarate dihydrate) powder inhaler 6 pg/puff, 12 pg/puff... 

FEV, forced expiratory volume in 1 second PEF, peak expiratory flow MDI, metered-dose inhaler DPI, dry powder inhaler. 

D NOTE Inhaled dry powder capsules require a different inhalation technique. To use a dry powder inhaler, it is important to close the mouth tightly around the mouthpiece of the inhaler and to inhale rapidly. 

The metering of dry powder inhalers is closely linked to the device itself and may be divided into three common systems capsules, multidosing blister packs, and reservoir systems. The consideration that goes into these metering systems include convenience to the patients, stability on storage, compatibility with product, and ease of filling. 

The performance of a dry powder inhaler involves evaluation of component compatibility and influence on device performance. The performance of commercial passive inhaler devices is influenced by the pressure drop generated by a patient during an... 

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. 

Table 6 Characteristics for Selected Passive Dry Powder Inhalers...

AR Clark, AM Hollingworth. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers—implications for in vitro testing. J Aerosol Med 6 99-110, 1993. 

KIL Wetterlin. Turbuhaler a new powder inhaler for administration of drugs to the airways. Pharm Res 5 506-508, 1988. 

USP24. <601 > Aerosols, Metered Dose Inhalers, and Dry Powder Inhalers. The United States Pharmacopoeia and National Formulary 1895-1912, 2000. 

Draft Guidance for Industry-Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products Chemistry, Manufacturing, and Controls Documentation, Nov. 13, 1998. 

M Vidgren, J Arppe, P Vidgren, P Vainio, M Silvasti, H Tukiainen. Pulmonary deposition of 99mTc-labelled salbutamol particles in healthy volunteers after inhalation from a metered-dose inhaler and from a novel multiple-dose powder inhaler. S.T.P. Pharm Sci 4 29-32, 1994. 

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

Administration via metered-dose inhaler (MDI) or dry-powder inhaler is at least as effective as nebulization therapy and is usually favored for reasons of cost and convenience. Refer to Table 80-1 in Chap. 80 for a comparison of the available agents. 

Vidgren, M.T., Karkkainen, A., Paronen, T.P and Kajjalainen, P. (1987). Respiratory tract deposition of "Tc-laheled drug particles administered via a dry powder inhaler. Int J Pharmaceut 39 101-105. 

Liquid instillation and nebulised aerosols are the most common methods for pulmonary administration to experimental animals [22, 54, 109, 134], The use of pressurised metered dose inhaler (pMDIs) and dry powder inhaler (DPIs) in preclinical studies is limited by the need for formulation development, which often cannot be performed in early drug discovery due to short supply of test materials. A number of alternative techniques for intra-tracheal administration of coarse sprays and powder formulations have been described [9, 15, 21, 36, 71, 80, 99, 138],... 

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. 

Hancock et al.63 reported a comprehensive review of a wide variety of pharmaceutical powders. Investigation of electrostatic properties of the drug substance or drug-excipient mixtures during preformulation has been recommended.64 Such studies may be particularly relevant for dry powder inhalation systems. 

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 7 More Recent Dry Powder Inhalation Systems ... 

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

Wong, D.Y.T., Wright, P., and Aulton, M.E., Influenee of Drug Partiele Size on the Performance of Dry Powder Inhalations of Nedoeromil Sodium, Proc. 14 th Pharmaceutical Technol-ogy Conference, Barcelona, 3 86-108 (1995). 

Rogerson, C., The Design and Production of Microparticles for Inhalation, Proc. Recent Advances in Dry Powder Inhalers, London, 1996. 

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