Packaging inhalation drug 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 drug products, also referred to as orally inhaled and nasal drug products (OINDPs including inhalation aerosols and solutions, nasal aerosols and sprays), have a high likelihood of packaging component-dosage form interaction,and therefore have individual USFDA guidance documents. As an example, consider the metered dose inhaler (MDI), shown... 

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. 

For the use of an inhaled medication (e.g., p2-agonists, corticosteroids, antivirals, cromolyn, etc.), it is crucial for the child and parents to understand the mechanism of the metered dose inhaler (MDI) or nebulizer, if used. The package insert should also be reviewed for information about the specific drug product. A decision may also need to be made as to whether a spacer may be needed for use with the medication canister. 

To evaluate inhalation toxicity in situations where workers are exposed to various concentrations and durations of a drug vapor, aerosol, or powder in the work environment during manufacturing or packaging, a more comprehensive determination of E(COso or L(Ct)so values are used. The E(Ct)50 or L(Ct)so values are statistically derived values that represent the magnitude of exposure, expressed as a function of the product of C and t, that is expected to affect or kill less than 50% and more than 50% of the animals. The other curve represents exposures that kill 50% or more than 50% of each group of animals (Irish and Adams, 1940). 

---