In Vitro-In Vivo Correlation Of Amorphous Solid Dispersion Enabled Itraconazole Tablets

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Limited reports exist on in vitro-in vivo correlation (IVIVC) for immediate-release (IR) formulations.
• Few studies investigate the impact of formulation and processing on spray-dried dispersion (SDD)-based tablets' human pharmacokinetics (PK).
• Commercial successes highlight the need to understand bioavailability enhancement in SDD tablets.

Purpose of the Study:

• To explore formulation and process factors influencing bioavailability enhancement of IR itraconazole SDD tablets.
• To establish an FDA Level A IVIVC for predicting in vivo PK performance from in vitro dissolution.

Main Methods:

• Employed a direct, differential-equation-based IVIVC model.
• Utilized an oral solution for post-dissolution disposition analysis.
• Tested Fast-, Medium-, and Slow-release tablets with specific in vitro dissolution conditions (USP simulated intestinal fluid, pH 6.4).

Main Results:

• The developed IVIVC met FDA internal predictability standards for Level A correlation.
• In vitro dissolution involved particle trituration to simulate in vivo disintegration differences.
• Model credibility was assessed through verification and validation, considering context and risk.

Conclusions:

• This is the first study to successfully develop an FDA Level A IVIVC for an amorphous solid dispersion.
• Assessed the influence of polymer grades, disintegrant levels, and dry granulation on SDD tablet performance.
• The findings provide a robust model for predicting human PK of itraconazole SDD tablets.