Inhalation dry powder inhalers

Specific considerations for container/closure system components for specialized delivery systems such as metered dose inhalers, dry-powder inhalers, disposable pen injectors, transdermal patches, or other novel dosage forms... 

Table A17.2 Key features of metered dose inhalers, dry powder inhalers and spacers...

Fink, J.B. Metered-dose inhalers, dry powder inhalers, and transitions. Respir. Care 2000, 45 (6), 623-635. 

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

Nasal spray Inhalation spray Inhalation solutions and suspensions Metered dose inhaler MDI Dry powder inhaler DPI, device metered Dry powder inhaler DPI, pre-metered Not included Non-pressurized metered dose nasal spray Nasal single use sprays Non-pressurized metered dose inhaler Product for nebuhzation (single and multiple use) Pressurized metered dose nasal sprays Pressurized metered dose inhaler Dry Powder Inhaler, device metered Nasal powders, device metered Dry Powder Inhaler, pre-metered Nasal drops (single and multiple use)... 

Stability test Pressurized metered dose nasal spray Pressurized metered dose inhaler Dry powder inhaler and nasal powders, device metered Dry powder inhaler pre-metered... 

Same as SC insulin Inhalation (dry powder inhaler) Diabetes Q Ci... 

Fire Hazards - Flash Point Not pertinent. This is a combustible solid Flammable Limits in Air (%) Not pertinent Fire Extinguishing Agents Graphite, sand, or any other inert dry powder Fire Extinguishing Agents Not To Be Used Water Special Hazards of Combustion Products Combustion results in beryllium oxide fumes whieh are toxic to inhalation Behavior in Fire Powder may form explosive mixture in air Ignition Temperature (deg. F) Not pertinent Electrical Hazard Not pertinent Burning Rate Not pertinent. 

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...

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. 

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. 

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. 

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