Modeling of Adhesion in Tablet Compression at the Molecular Level Using Thermal Analysis and Molecular Simulations.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Tablet sticking during compression is a critical manufacturing issue.
• Understanding molecular interactions is key to predicting and preventing adhesion.
• Previous studies lack a combined thermal analysis and molecular simulation approach.

Purpose of the Study:

• To investigate the molecular basis of drug adhesion and sticking propensity.
• To correlate thermal analysis data with molecular simulation results for ibuprofen, flurbiprofen, and ketoprofen.
• To establish a predictive model for drug-surface interactions during tablet compression.

Main Methods:

• Utilized Differential Scanning Calorimetry (DSC) to determine the work of adhesion.
• Employed molecular simulations (Materials Studio) to calculate interaction energies with an iron surface.
• Investigated ibuprofen, flurbiprofen, and ketoprofen as model drug substances.

Main Results:

• Established a linear relationship between enthalpy of vaporization and sample mass for accurate thermal analysis.
• Determined threshold masses: ibuprofen (107 μg), flurbiprofen (112 μg), and ketoprofen (222 μg).
• Simulated work of adhesion rank order: ketoprofen > ibuprofen > flurbiprofen, consistent with experimental threshold masses.

Conclusions:

• Thermal analysis provides a viable method to assess drug sticking propensity at the molecular level.
• Molecular simulations accurately predict drug-surface interaction energies.
• The combined approach offers a powerful tool for optimizing tablet manufacturing processes and preventing sticking.