Dissolution testing
As usual for an RDD meeting, the Digital RDD 2020 program devotes a significant portion of its time to topics related to OINDP development, especially characterization and formulation of inhaled and nasal drugs. One of the sessions, on the topic of “Clinically Relevant Testing in NDA and Lifecycle Submissions,” includes a discussion about dissolution testing that has been ongoing for several years.
The FDA’s Renish Delvadia addresses these issues in his talk on “Clinically Relevant Specifications for Orally Inhaled Drug Products: Challenges and Opportunities,” talking about the use of clinically relevant drug product specifications (CRDPS) to balance between the possibility of specifications that put patients at risk because they are too broad and specifications that put sponsors at risk because they are too narrow.
Noting that, “Our understanding about the critical quality attributes that are relevant for the in vivo performance of orally inhaled drug products has evolved since the approval of the first MDI in the late 1950s,” Delvadia acknowledges that in vivo performance of OIDPs is affected by numerous variables in formulation, manufacturing, the device, and handling and that the standard aerodynamic particle size distribution (APSD) and delivered dose uniformity (DDU) tests “do not necessarily consider the in vivo intra- and inter-subject variability.”
He addresses the current and potential uses of realistic throat models, simulated inhalation profiles, and in vitro dissolution testing and suggests that a standardized sample collection method that takes both APSD and DDU into account should be a priority. Like several of the other presenters, he mentions the PQRI effort to develop a BCS (biopharmaceutical classification system) for inhaled drugs (iBCS), though he cautions that the feasibility of such a system is not yet known.
Other presentations on the use of dissolution testing include Per Bäckman of Emmace Consulting‘s talk “Pulmonary Drug Dissolution, Regional Retention & Systemic Absorption: Understanding their Interactions through Mechanistic Modeling” in which he discusses the opportunities presented by mechanistic models if such a model can be validated and a talk on “Dissolution Tests for Oral Inhalers: Challenges with Method Development and Specifications” by Andreea Floroiu of Phast Development, who describes her work with the DissolvIt system from Inhalation Sciences.
