Ensuring Safe and Stable Inhaled Medicines

Stability studies play an important role in inhalation drug development

26 April 2016

Inhaled medicines are growing in popularity as they provide an effective and patient-friendly means of delivering local and systemic therapies to the body. As such, laboratory testing of inhaled products is becoming increasingly critical to assuring the safety and efficacy of these products.

Stability studies play an important role in inhalation medicine development, arguably more so than other delivery systems. In addition to allowing evaluation of the chemical stability of the active drug(s), stability studies enable recommended storage conditions, retest intervals and shelf lives to be established. For inhaled medicines, in particular, these studies allow assessment of the effect of temperature and humidity, which can adversely affect both the size distribution of the delivered medicine by reducing the dosage at the target area of delivery and the effectiveness of drug delivery from the device.

Dissolution, bioavailability and external factors

For nebulisers, pressurised metered-dose inhalers (pMDIs), and dry-powder inhalers (DPIs), measurement of particle / droplet size throughout a stability study is a key issue, as - in addition to governing the target area of the delivery – this factor can influence the rate of dissolution and bioavailability at the target site. The limit for moisture content should be established based on results of the stability study to determine if this is stable throughout the shelf life of the product, or if changes in moisture content result in changes to the effective delivery of the drug. Normally, during early development, accelerated feasibility studies are designed and conducted to ensure that any potential excipient compatibility issues have been identified; however, the effect of temperature and humidity on the performance of the formulation / device combination needs to be understood as early as possible.

Storage and packaging

If the performance of a product - for example a pressurised metered dose inhaler - is considered to be influenced by whether it is stored upright or not ('the storage orientation') the containers should be stored in various orientations during the stability study in order to determine the effect of orientation.

If the product includes secondary packaging in order to protect it from light and/or humidity (for example, a dry powder inhaler inside a foil overwrap), the length of time that the product may be used after the protective packaging has been removed should be supported by stability results. The studies should involve removing the product from the protective packaging close to the end of its shelf life and testing the exposed product against the drug product specifications.

Outsourcing Stability Studies

Outsourcing stability storage is a highly efficient way to manage your costs, however, it is important to establish the optimum stability study protocol for your product, and it is critical to work closely with your Contract Research Organisation (CRO) for a successful study.  After many years of working with many clients around the world on many stability study protocols, we know there are certain questions that you can ask of your team and of your CRO, in order to ensure your study runs like clockwork.

These questions include "what information should be included in the stability protocol?", "what in-house knowledge exists which the CRO does not know?"  and "what happens exactly to your samples when they go to a contract laboratory for storage?"  These, and other important questions, are the topic of our On Demand Webinar "Outsourcing Stability Studies to Contract Laboratories; Optimising Success".

Access our webinar now to learn more about best practice and steps to consider to ensure your stability protocol covers all the points a contract laboratory will need to know to make your study run like clockwork.

More Information:

Having graduated from Liverpool John Moore's University with a degree in Analytical Chemistry, Kerry Bradford spent brief spells working for ICI chemicals and the University of Cambridge Chemistry Department before joining Melbourn Scientific in 1997.  Her current role at Intertek Melbourn is that of Laboratory Manager and she works closely with the stability storage team. Since the inception of this team over 10 years ago, she has gained experience working with a large number of clients and product types.