Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• The molecular state of active pharmaceutical ingredients (APIs) is critical for drug efficacy and stability.
• Understanding API behavior in pharmaceutical formulations is essential for drug development and quality control.

Purpose of the Study:

• To review fundamental physicochemical studies on API molecular states in pharmaceutical dosage forms.
• To evaluate the impact of mechanochemical processing on API molecular states.
• To explore methods for investigating drug-excipient interactions.

Main Methods:

• Review of physicochemical studies.
• Mechanochemical evaluation of API-excipient mixtures (grinding).
• Sealed-heating method and use of mesoporous materials.
• Characterization techniques including powder X-ray diffraction, thermal analysis, IR, solid-state fluorometry, and NMR.

Main Results:

• Grinding APIs with pharmaceutical additives can induce amorphization, complex formation, or nanoparticle formation.
• The observed changes depend on the specific combination of APIs and additives.
• Various analytical techniques are effective for investigating molecular states and interactions.

Conclusions:

• Mechanochemical processing offers a route to modify API molecular states and potentially enhance drug properties.
• Understanding and controlling API molecular states is crucial for pharmaceutical formulation.
• Advanced analytical methods are vital for characterizing drug-excipient interactions.