Abstract

Process Analytical Technology (PAT) plays a key role in modern continuous manufacturing. However, in-line tools to measure ribbon solid fraction (SF_ribbon) in roll compaction remain uncommon. Therefore, this study introduces a PAT approach for in-line SF_ribbon measurement during roll compaction using Ibuprofen DC100.

The authors investigated different placebo formulations with various binders and one active pharmaceutical ingredient formulation. Using in-line laser triangulation, they measured ribbon thickness immediately after compaction. This allowed direct calculation of ribbon elastic recovery (ER_in-line) while ribbons remained on the roll surface.

They observed that the ratio between total elastic recovery and in-line recovery (ER_ratio) depends on the formulation but not on process parameters. Consequently, ER_ratio can predict SF_ribbon if the solid fraction at gap width (SF_gap) is known. They determined SF_gap through ribbon mass flow measurement and the Midoux model, a simplified Johanson approach. Both prediction models showed strong agreement between calculated and measured SF_ribbon.

Materials

The scientific team selected the following materials for the study:

• Microcrystalline cellulose (MCC, Vivapur® 102), hydroxypropyl cellulose (HPC, NISSO HPC SSL SFP), and polyvinylpyrrolidone K25 (PVP, Kollidon® 25) as binders.

• Dibasic calcium phosphate anhydrous (DCPA, DI-CAFOS® A60) as filler.

• Ibuprofen (Ibuprofen DC100, IPC Process-Center GmbH & Co. KG, Germany) as the active pharmaceutical ingredient.

These materials allowed us to study direct compression in roll compaction with Ibuprofen DC100 and evaluate its effect on tablet formulation efficiency.

Role of Ibuprofen DC100 in Roll Compaction

The authors used Ibuprofen DC100 as a model drug to test direct compression methods. Its properties make it suitable for studying tablet quality, optimizing manufacturing processes, and improving drug release profiles. Moreover, it helps explore simpler production processes, reduce costs, and maintain high tablet quality.

Methodology for Ribbon Solid Fraction Measurement

The team applied in-line laser triangulation as a PAT tool to measure ribbon thickness and elastic recovery during roll compaction. The process included:

1. Measuring ribbon thickness immediately after compaction.

2. Calculating in-line elastic recovery (ER_in-line).

3. Determining ER_ratio as a predictor for SF_ribbon.

4. Calculating SF_gap using ribbon mass flow measurements and the Midoux model.

These steps allowed accurate prediction of SF_ribbon during roll compaction with Ibuprofen DC100. In addition, the results confirmed the reliability of both prediction models.

Conclusion

This study established in-line laser triangulation as a PAT tool to predict ribbon solid fraction during roll compaction using Ibuprofen DC100. They found that ER_in-line varies by measurement spot, yet laser position does not affect SF_ribbon predictions. The ER_ratio depends on formulation and remains unaffected by process parameters. Both mass flow and Midoux model approaches provided accurate SF_ribbon estimates.

Overall, roll compaction with Ibuprofen DC100 can be efficiently monitored and optimized using in-line PAT. Therefore, manufacturers can improve tablet consistency, reduce variability, and enhance production efficiency.