Drug powder inhalers

Biddiscombe, M.F., Melchor, R., Mak, V.H.F., Marriott, R.J., Taylor, A.J., Short, M.D., and Spiro, S.G., The lung deposition of salbutamol, directly labelled with technetium-99m, delivered by pressurized metered dose and drug powder inhalers, Int. J. Pharm., 91 111-121... 

In both cases, pneumothorax occurred with a delay after cocaine inhalation. The authors suggested that it was therefore unlikely that these cases of pneumothorax were due to direct traumatic effects of the drug powder inhaled, to barotrauma due to exaggerated inspiration, or to a Valsalva maneuver. Histological examination in both cases showed small foreign body granulomas with polarized material in the subpleural parenchyma. The authors proposed that the pleural damage could have been directly caused by a filler substance known as mannite (a fine white powder comprised of insoluble cellulose fibers). 

As a consequence of the suppression or reduced use of CFC propellants, a new kind of dosage form is under worldwide development drug powder inhalers (DPIs). The metered dose inhalers (MDIs) will probably be replaced by these. The MDIs were formulated several years ago. A drug in powder form (with a particle size close to 5 pm) was suspended in propellant 11 with a surfactant. Propellant 12 was added to the can after closure. 

Figure 5 Graph demonstrating in vitro reproducibility of the emitted dose for a radiolabeled drug powder inhaled at two different inspiratory flowrates. Although the mean dose of drug and radioactivity varied between study days, the coefficient of variation for the emitted doses of drug or radioactivity on each study day was low. The amount of radioactivity used in the labeling of the powder varied with the specific activity of the 99mTc04 supply on each labeling day [86].

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

Draft Guidance for Industry-Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products Chemistry, Manufacturing, and Controls Documentation, Nov. 13, 1998. 

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],... 

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. 

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. 

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). 

Moren, F., In vitro and in vivo Performance of Powder Inhalers, Proc. Respiratory Drug Delivery II, Interpharm Press, Buffalo Grove, IL, 1990. 

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. 

Vidgren, M., Paronen, P., Vidgren, P., Vainio, P., and Nuutinen, J., Radiotracer evaluation of the deposition of drug particles inhaled from a new powder inhaler, Int. J. Pharm., 64 1-... 

As described in Section 3.3 in more detah, particles in the aerosol cloud should preferably have an aerodynamic diameter between 0.5 and 7.5 pm. Currently three different types of devices are used to generate aerosol clouds for inhalation nebulizers (jet or ultrasonic), (pressurized) metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). The basic function of these three completely different devices is to generate a drug-containing aerosol cloud that contains the highest possible fraction of particles in the desired size range. 

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 are generally described as breath actuated devices, because the inspiratory airstream releases the dose from the dose system and supplies the energy for the generation of fine drug particles from the powder formulation. Because the efficiency of dose release and powder disintegration increases with increasing inspiratory flow rate for most DPIs, these devices would be better described as breath controlled devices. In Section 3.9, the effect of resistance and clinical conditions on the flow curve and relevant flow parameters for DPIs are discussed. 

In Section 3.5.3, dry powder inhalers have been referred to as breath-controlled devices. The efficacy of dry powder inhalation is a function of many factors, influencing the delivered dose of fine particles and the deposition of these particles in the respiratory tract. Figure 3.4 shows that DPI performance is influenced both directly and indirectly by the design of the inhalation system. The powder formulation, the dose (measuring) system and the powder disintegration principle have to be designed correctly for release of sufficient fine drug particles in... 

Excretion - The terminal elimination half-life is between 5 and 6 days following inhalation. After dry powder inhalation, urinary excretion is 14% of the dose, the remainder being mainly nonabsorbed drug in the gut, which is eliminated via the feces. The renal clearance of tiotropium exceeds the Ccr, indicating active secretion into the urine. After chronic, once-daily inhalation by COPD patients, pharmacokinetic steady state was reached after 2 to 3 weeks with no accumulation thereafter. 

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. 

U.S. Food and Drug Administration (FDA) (1998, Oct.), Guidance for industry Metered dose inhaler and dry powder inhaler drug products, FDA Washington, DC. 

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