Microscope-enabled disc dissolution system: Concordance between drug and polymer dissolution from an amorphous solid...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery Systems

Background:

• Amorphous solid dispersions (ASD) are crucial for enhancing drug solubility.
• Predicting the drug load dispersibility limit in ASDs is essential for formulation development.
• Existing methods for assessing ASD performance often lack real-time visual feedback.

Purpose of the Study:

• To develop a novel microscope-enabled disc dissolution system (MeDDiS) with a larger dissolution volume (900 mL).
• To evaluate the concordance between imaging data from MeDDiS and traditional dissolution measurements.
• To assess MeDDiS's ability to predict drug and polymer release profiles across varying drug loads in ASDs.

Main Methods:

• Fabrication of ASD discs containing ritonavir and PVPVA at different drug loads (5-50%).
• Utilizing a digital microscope integrated into a 1-liter dissolution vessel (MeDDiS) for real-time imaging.
• Quantifying changes in disc diameter over time and measuring ritonavir and PVPVA release.

Main Results:

• MeDDiS imaging demonstrated strong concordance with measured drug and polymer dissolution profiles.
• A critical drug load 'cliff' was identified around 30% ritonavir load, below which release significantly decreased.
• MeDDiS successfully predicted both high and low release profiles above and below this identified drug load limit.

Conclusions:

• The developed MeDDiS provides a promising tool for real-time assessment of ASD dissolution behavior.
• MeDDiS imaging can accurately predict drug and polymer release, aiding in the determination of optimal ASD drug loads.
• This method offers valuable insights into ASD performance, particularly around critical formulation limits.