Inhalation drug products

Draft Guidance for Industry-Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products Chemistry, Manufacturing, and Controls Documentation, Nov. 13, 1998. 

Figure 6.3 Simple schematic to illustrate the hierarchy of complexity of systems used for preclinical absorption and disposition investigations of inhaled drug products. Interspecies variation should be considered. In silico modelling based on human data and use of the human perfused lungs can provide complex information regarding human absorption and disposition data.

Poochikian, G. and Bertha, C.M., Regulatory view on current issues pertaining to inhalation drug products, Respiratory Drug Delivery VIII Conference, Vol. 1, 2000, pp. 159-164 [www.rddonline.com]. 

Pharmaceuticals, for the purpose of this book, means chemical compounds that are used in pharmaceutical production. This can comprise the active ingredient, which is also called active pharmaceutical ingredient (API) or drug substance or drug product and the inert pharmaceutical ingredients (excipients) that are used to formulate a drug product in the form of tablets, capsules, ointments, creams, lotions, parenterals, inhalers, and a variety of drug delivery systems. 

Principles of fluid and particle dynamics in the respiratory tract (physical and anatomical parameters) are also discussed, as they are the starting point for the development of drug products for inhalation. In fact, they set the conditions used for in vitro and in vivo testing of inhalation systems and define the specifications for new inhalation systems. 

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. 

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

Stress Testing (drug product) — Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photostability testing (see ICH Q1B) and specific testing of certain products (e.g., metered dose inhalers, creams, emulsions, refrigerated aqueous liquid products). 

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. 

Inhalation solution and suspension drug products are typically aqueous-based formulations that contain therapeutically active ingredients and can also contain additional excipients. Aqueous-based oral inhalation solutions and suspension must be sterile (21 CFR 200.51). Inhalation solutions and suspensions are intended for delivery to the lungs by oral inhalation for local or systemic effects and are used with a specified nebulizer. Unit-dose presentation is recommended for these drug products to prevent microbial contamination during use. The container closure system for these drug products consists of the container and closure and can include protective packaging such as foil overwrap. 

Products, as do Kumi and Booth (17). De George et al. offer guidance on excipients used in inhalation drug products (18). 

FDA. Guidance for industry metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products. CDERGUID 2180dft.wpd, Nov 1998, http //www.fda.gov/cder/gui-dance/2180dft.pdf, 1998. 

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