Formulation of tablets containing an ‘in-process’ amorphized active pharmaceutical ingredient

Abstract

The aim of this work was a preliminary study of the “in-process” amorphization of clopidogrel hydrogensulfate (CLP) as model drug during the production of tablets as dosage form. A solvent method was used for amorphization and the crystalline phase of CLP was detected by differential scanning calorimetry; the physical parameters of fresh and stored tablets were investigated. For the amorphous form, Aerosil 200 was selected as crystallization inhibitor as the most suitable of eight auxiliary agents. The optimum composition of the product for amorphization in the scaling-up process (100-fold) was 7 parts of CLP to 3 parts of Aerosil 200. In this scaled-up product, the amorphous CLP was fixed on the surface of microcrystalline cellulose. The tablet form further stabilized the amorphous form. Finally, the steps of an “in-process” amorphization are given as a protocol, which can promote stabilization of an amorphized active pharmaceutical ingredient.

Keywords::

• Aerosil 200
• amorphous
• clopidogrel hydrogensulfate
• crystallization inhibitor
• ‘in-process’ amorphization

Acknowledgment

The help of Ottó Berkesi and Gabriella Farkas is gratefully acknowledged for the measurement of FT-IR analysis.

Declaration of interest

This work was supported by TÁMOP-Hungary research project: Development of teranostics in cardiovascular, metabolics, and inflammatory diseases (TÁMOP-4.2.2-08/1-2008-0013).