Towards in vitro - In vivo correlation models for in situ forming drug implants

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Biopharmaceutics

Background:

• In vitro-in vivo correlation (IVIVC) is crucial for predicting drug performance and reducing clinical trials.
• Developing IVIVCs for in situ forming implants is difficult due to distinct in vitro and in vivo drug release profiles.
• This complexity arises from unique drug release mechanisms inherent to these dosage forms.

Purpose of the Study:

• Identify critical attributes of in vitro release testing methods impacting drug release from in situ forming implants.
• Optimize in vitro release methods to establish Level A IVIVCs for risperidone in situ forming implants.
• Enhance the predictability of drug product performance based on in vitro data.

Main Methods:

• Investigated risperidone in situ forming implants as a model system.
• Employed novel dissolution methods using Teflon adapters and GF/F membranes or a Glass slide adapter.
• Evaluated the impact of surface-to-volume ratio, water uptake, phase separation rate, and mechanical pressure on drug release.

Main Results:

• Surface-to-volume ratio and water uptake were identified as critical in vitro method attributes.
• A Glass slide adapter-based method successfully generated bio-relevant degradation and in vitro release profiles.
• A Level A IVIVC was successfully developed and validated for risperidone implants using rabbit models and different PLGA molecular weights.

Conclusions:

• Optimized in vitro dissolution methods can overcome challenges in developing IVIVCs for in situ forming implants.
• The Glass slide adapter method provides a bio-mimicking environment crucial for accurate in vitro release prediction.
• This work establishes a foundation for developing robust IVIVCs for in situ forming implants, aiding regulatory submissions and drug development.