Effect of Processing on Celecoxib and Its Solvates

Abstract

Pharmaceuticals mostly exist in crystalline form and exhibit the phenomenon of differential crystal packing and configurational arrangements of molecules, called polymorphism. Pharmaceutical processing by introducing significant amount of stress alters the molecular interactions in the system engendering polymorphic transformations. The energy supplied by these processing steps tends to overcome the energy barriers between different solid‐state forms, thus yielding undesirable changes in the physicochemical and material characteristics of drugs or their dosage forms. Therefore, the role of these unit processes in solid‐state transformations must be cautiously studied and if required appropriate controls should be used to monitor such events. The present study was aimed at studying the effect of major energy imparting pharmaceutical unit processes, like size reduction, wet granulation, consolidation, and compression on solid‐state transformation of Celecoxib, a selective cyclooxygenase‐II inhibitor and its N,N‐dimethyl acetamide and N,N‐dimethyl formamide solvated forms. A qualitative estimation of crystal transformation in processed samples was performed using DSC, microscopy, FTIR spectroscopy, and XRPD. FTIR was also applied for the development of a quantification method to find the percentage of transformation in N,N‐dimethyl acetamide solvated form during compression.

Keywords:

• Solvates
• Mechanical processing
• Transformation
• Solid‐state characterization
• FTIR