Functional performance of silicified microcrystalline cellulose versus microcrystalline cellulose: a case study

Abstract

Background: During the development of a tablet dosage form of an investigational compound, R411, several aspects were identified as critical quality attributes that required optimization. The use of nonsolvent processing prevented the moisture-induced physical changes in the drug product but presented manufacturing challenges related to sticking during compression and slowdown in dissolution after storage at stress conditions. Aim: The aim of this study was to evaluate silicified microcrystalline cellulose (SMCC), microcrystalline cellulose (MCC), and physical mixture of MCC–colloidal silicon dioxide (MCC/CSD at 98:2 ratio) as extragranular compression aids to address the processing and dissolution stability issues of this formulation. Methods: The compactibility and stickiness upon compression over extended period of time as well as the dissolution of R411 formulations incorporating the aforementioned compression aids were investigated. In addition, the water sorption/desorption properties of these compression aids were determined. Results: All formulations showed comparable compactibility irrespective of the compression aid used. Nevertheless, MCC alone or in a physical mixture with CSD showed sticking of the lower punches, whereas SMCC resulted in clean punch surface during extended compression runs. Furthermore, the three compression aids were compared for their effect on dissolution stability after storage at stress conditions. The formulations containing SMCC provided superior dissolution stability over the other compression aids evaluated in the study. Conclusions: Novel functionalities of SMCC are presented in terms of sticking prevention while having the most beneficial effect on dissolution stability in R411 formulation.

Keywords:

• Anti-adherent
• colloidal silicon dioxide
• compactibility
• compression aid
• microcrystalline cellulose
• silicified microcrystalline cellulose

Acknowledgments

The authors gratefully acknowledge Dr. Shangdong Zhan for the dissolution support and Mr. Maurice Munroe for hygroscopicity studies at Roche and Mr. J. Zeleznik at JRS Pharma for the technical data.

Declaration of interest: The authors report no conflicts of interest.