A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets.

Area of Science:

• Pharmaceutical Sciences
• Process Analytical Technology (PAT)
• Materials Science

Background:

• A critical need exists for on-line/in-line tools to predict pharmaceutical tablet dissolution and disintegration during manufacturing.
• Tablet porosity is a fundamental critical quality attribute influencing drug mass transport, disintegration, and dissolution.
• Existing methods lack the speed and non-destructive nature required for real-time manufacturing assessment.

Purpose of the Study:

• To develop and validate a rapid, non-destructive method for measuring tablet porosity.
• To establish terahertz spectroscopy as a tool for predicting tablet disintegration and dissolution characteristics.
• To enable real-time release testing (RTRT) for immediate-release (IR) pharmaceutical tablets.

Main Methods:

• Developed a terahertz spectroscopy measurement protocol for total tablet porosity.
• Employed a fast, non-destructive transmission method requiring no sample preparation.
• Validated the method across diverse immediate-release formulations (ibuprofen, indomethacin) with varying geometries and debossing.

Main Results:

• Terahertz spectroscopy accurately measured total tablet porosity in under a second per sample.
• Excellent correlation was observed between terahertz-derived porosity and drug dissolution (time to 50% release) and disintegration times.
• The method predicted disintegration and dissolution without the need for complex chemometric models.

Conclusions:

• Terahertz spectroscopy offers a robust and rapid method for assessing tablet porosity.
• This technique effectively predicts critical tablet performance attributes like dissolution and disintegration.
• The terahertz porosity method is a promising candidate for automated, at-line/on-line sensors for real-time release testing of IR tablets.