Purpose: The purpose of this study was to follow the disintegration of tablets and subsequent deaggregation of granules to primary particles using Focused Beam Reflectance Measurements (FBRM) to get a better mechanistic understanding of in vivo performance differences between a tablet manufactured by wet granulation compared to roller compaction.
Methods: 25 mg strength tablets were prepared by either high shear wet granulation ( WG) or roller compaction (RC) process using the same lot of drug substance. Formulations utilized very similar compositions; the wet granulation did incorporate PVP K30 as a binder. Excipients include avicel, lactose, ac-di-sol, SLS and SSF.
Tablets were evaluated by disintegration, dissolution and assessed in vivo in fasted male beagle dogs using a cross-over design. All disintegration and dissolution assessments were evaluated in fasted state small intestinal fluid (FaSSIF) at 37°C.
Tablet disintegration was assessed in an Erweka ZT42 disintegration tester using a USP/Pharm.Eur./JP compliant basket rack assembly. One tablet was dropped into the basket, this was dropped into 900 ml of FaSSIF; disintegration time recorded when basket was empty.
Dissolution was assessed in 900 ml FaSSIF, USP II, 37 C 65 RPM.
Tablet and granule disintegration were assessed by FBRM. 2 tablets were dropped into a reaction vessel containing 200 ml of FaSSIF, stirred at 175 RPM and 37°C. The time of disintegration was assessed visually and the FBRM was used to track chord length distribution.
Results: The traditional disintegration method showed no differences between wet granulated and roller compacted tablets. The dissolution showed some difference in dissolution rate; with wet granulated tablets exhibiting a faster API dissolution relative to roller compacted tablets. FBRM showed clear differences in the generation of primary particles; the wet granulated formulation did generate a higher count of primary particles relative to the roller compacted tablets.
Conclusion: Visual differences between deaggregated WG and RC tablets are apparent. The FBRM confirmed the hypothesis that WG Tablets deagglomerate faster than RC tablets. The FBRM shows that WG tablets produce more primary particles than RC tablets. The FBRM is a method to measure semi-quantitative differences in the primary particles generated from tablets and can be incorporated as an additional in vitro tool to evaluate deaggregation