In Silico Modelling to Aid Product Development Strategies for Low Global Warming Potential Metered Dose Inhalers
Neha Patel1 & Alexander Richford1
1Kindeva Drug Delivery Ltd., Derby Road, Loughborough, Leicestershire, LE11 5SF, United Kingdom
Summary
The current expectation is that new metered dose inhalers (MDIs) containing existing drug substances re-formulated with alternative low global warming potential (GWP) propellants (HFA-152a and HFO-1234ze) will have similar in-vitro and/or pharmacokinetic (PK) performance to the already-approved HFA-134a and HFA-227 reference products. In-silico PK modelling provides a development tool for predicting which new product configurations are most likely to be comparable to existing products. Preludium™ has been used to calculate lung regional deposition from clinically relevant in-vitro cascade data, which in turn has been used to develop an inhalation PK model for salbutamol products that can predict PK plasma profiles, differentiate product strengths and different inhalation dosage forms. An exponential error model has then been applied to the PK model to simulate expected between (BSV) and within subject variability (WSV).
In-silico simulation has been used to compare various low GWP MDI test product configurations in terms of predicted PK performance. Using the exponential error model, it is possible to simulate variance that could be expected in a PK study and establish which test product configuration is most likely to achieve PK bioequivalence (BE) compared to a reference product. This may be particularly useful for the development of bioequivalent new low GWP MDI products.