Powder metered dose inhaler

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

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

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Draft Guidance for Industry-Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products Chemistry, Manufacturing, and Controls Documentation, Nov. 13, 1998.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

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],... 

To measure lung deposition by imaging, the aerosol must be first labelled or tagged with a suitable radionuclide. Radiolabelling techniques have been developed for current inhalation products including nebulizers, propellant-driven metered dose inhalers, and dry powder inhalers. 

Zainudin, B.M.Z., Biddiscombe. M., Tolfree, S.E.J., Short, M., and Spiro, S.G., Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurized metered dose inhaler, as a dry powder, and as a nebulized solution, Thorax, 45 469-473 (1990). 

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. 

Table 3.3. Advantages and disadvantages of dry powder inhalers versus metered dose inhalers, partly from reference [14].

Table 8.2 30-min post-inhalation urinary salbutamol excretion (% inhaled dose) in nine subjects following inhalation of 4 X 100 mg salbutamol using a metered-dose inhaler (MDI) and a dry powder inhaler (DISK) ... 

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 ... 

Hindle M, Newton DAG, Chrystyn H Dry powder inhalers are bioequivalent to metered-dose inhalers. Chest 1995 107 629-33. 

Guidelines for the Diagnosis and Management of Asthma. Expert Panel Report 2. National Institutes of Flealth. National Heart, Lung, and Blood Institute. February 1997. htto //www.lunausa.ora/asthma/astnhlbi.html MDI = Metered dose inhaler. DPI = Dry powder inhaler. ... 

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... 

Ross DL, Schulz RK. Effect of inhalation flow rate on the dosing characteristics of dry powder inhaler (DPI) and metered dose inhaler (MDI) products. J Aerosol Med 1996 9(2) 215-26. 

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

Aerosols can be generated by three main drug delivery systems nebulizers, pressurized metered dose inhaler (pMDI), and dry powder inhaler (DPI). 

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

FDA. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products chemistry, manufacturing, and controls documentation. CDER/FDA, 1998. 

Goldberg S, Einot T, Algur N, Schwartz S, Greenberg AC, Picard E, Virgihs D, Kerem E. Adrenal suppression in asthmatic children receiving low-dose inhaled budesonide comparison between dry powder inhaler and pressurized metered-dose inhaler attached to a spacer. Ann Allergy Asthma Immunol 2002 89(6) 566-71. 

The Easyhaler (by Orion Pharma, Finland) and the Clickhaler (by Innovata pic, United Kingdom) are available at present in some European markets. Unlike the DPIs described earlier, these two reservoir-type inhalers meter the dose when the patient presses the top of the device similar to actuation of a pressurized metered-dose inhaler. Both devices contain a dose indicator, which is standard for reservoir multidose DPIs. Recently, Innovata presented the Twinhaler for asthma combination therapy, a new development based on the Clickhaler. This device does not require the combined drugs to be formulated in one powder blend but delivers two powder formulations from two reservoirs into one airflow path. 

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