Accelerated and Biopredictive In Vitro Release Testing Strategy for Single Agent and Combination Long-Acting...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Long-acting injectable (LAI) suspensions require robust methods for predicting in vivo performance.
• Current in vitro release testing (IVRT) strategies may not fully capture the complex release kinetics of LAI products.
• Accurate preclinical assessment is crucial for the development of novel LAI formulations.

Purpose of the Study:

• To develop an in vitro release testing (IVRT) strategy for predicting the preclinical performance of single agent and combination long-acting injectable (LAI) suspension products.
• To establish validated in vitro-in vivo correlations (IVIVCs) for LAI formulations.

Main Methods:

• Developed two accelerated IVRT methods using USP apparatus 2 to characterize distinct drug release phases (initial, intermediate, terminal).
• Employed specific agitation and suspension techniques to control surface area exposure and particle dispersion.
• Time-scaled in vitro release profiles and developed Level-A IVIVCs using deconvolution of rat plasma concentration-time data.

Main Results:

• Successfully characterized initial, intermediate, and terminal drug release phases within 48 hours using the developed IVRT methods.
• Established independently validated Level-A IVIVCs for each active pharmaceutical ingredient (API) and IVRT method.
• Demonstrated the ability of IVRT to predict in vivo performance of complex LAI suspensions.

Conclusions:

• The developed IVRT strategy provides a reliable framework for evaluating complex LAI drug release.
• This approach enables accurate prediction of in vivo performance during preclinical development.
• The validated IVIVCs support the use of these IVRT methods for LAI product characterization.