Enthalpy relaxation studies of two structurally related amorphous drugs and their binary dispersions

Abstract

Objective: The purpose of the current study was to evaluate the enthalpy relaxation behavior of valdecoxib (VLB) and etoricoxib (ETB) and their binary dispersions to derive relaxation constants and to understand their molecular mobilities. Methods: Solid dispersions of VLB and ETB were prepared with 1%, 2%, 5%, 10%, 15%, and 20% (w/w) concentrations of polyvinylpyrrolidone (PVP) in situ using differential scanning calorimetry (DSC). Enthalpy relaxation studies were carried out with isothermal storage periods of 1, 2, 4, 6, 16, and 24 hours at 40°C and 0% relative humidity (RH). Results: PVP increased the glass transition temperature (T_g) and decreased the enthalpy relaxation. Significant differences between two drugs were observed with respect to their relaxation behavior which may be due to differences in intermolecular interactions as predicted by Couchman–Karasz equation and molecular mobility. Kohlrausch–Williams–Watts equation was found to be inadequate in describing complex molecular relaxations in binary dispersions. The enthalpy relaxation behavior of VLB and ETB was found to be significantly different. PVP stabilized VLB significantly; however, its effect on ETB was negligible. The extent of enthalpy relaxation was found to correlate with hydrogen bonding tendency of the drug molecules. Conclusion: The outcome can help in rational designing of amorphous systems with optimal performance.

• Amorphous
• binary dispersions
• enthalpy relaxation
• glass transition temperature
• molecular mobility

Acknowledgments

The authors acknowledge Aarti drugs Ltd., Mumbai, India, for providing gift sample of VLB. Aditya Mohan Kaushal would like to acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, India for providing senior research fellowship.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of this paper.