Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Orally disintegrating tablets (ODTs) rely on specific excipient properties for functionality.
• Understanding nano-scale interactions of excipients like microcrystalline cellulose (MCC) and D-mannitol is crucial for ODT formulation.
• Physico-chemical and mechanical properties at the molecular level dictate macro-scale tablet performance.

Purpose of the Study:

• To investigate the adhesive/cohesive molecular and physical interactions of MCC and D-mannitol.
• To elucidate the nanoscopic features influencing powder densification and ODT functionality.
• To correlate nano/micro-scale excipient behavior with macro-scale ODT properties.

Main Methods:

• Atomic Force Microscopy (AFM) in contact and tapping modes to measure nano-adhesion, surface energy, topography, and roughness.
• Characterization of excipient-drug particle interactions.
• Analysis of ODTs using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), disintegration testing, Heckel, and tabletability studies.

Main Results:

• A strong correlation was found between inter-particle adhesive forces and tablet mechanical strength.
• Microcrystalline cellulose (MCC) exhibited higher micro-roughness and particle interlocking, leading to harder tablets.
• D-mannitol produced fragile tablets due to weak crystal structure and crystallite fragmentation during compression.
• AFM revealed microfibril structures in MCC, supporting its use as a disintegrant.

Conclusions:

• Excipient nano/micro-scale behavior directly relates to macro-scale ODT functionality.
• MCC's surface topography and mechanical properties contribute to robust ODTs.
• D-mannitol's crystalline fragility results in weaker ODTs.
• Understanding these fundamental interactions aids in optimizing ODT formulation and performance.