Characterization of pharmaceutical solids by scanning probe microscopy

Area of Science:

• Materials Science
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Understanding material properties is crucial for pharmaceutical formulation.
• Nanoindentation is a technique used to measure mechanical properties of materials.
• Characterizing soft/hard and plastic/brittle materials requires precise methods.

Purpose of the Study:

• To obtain force-displacement profiles of acetaminophen, potassium chloride, sucrose, and sodium stearate using a novel nanoindentation technique.
• To analyze the hardness and stiffness of these materials.
• To evaluate the utility of nanoindentation coupled with atomic force microscopy for preformulation studies.

Main Methods:

• Preparation of flat surfaces of four materials via melting or recrystallization.
• Utilizing a novel nanoindentation technique with a specific loading-hold-unloading profile (10s-2s-10s).
• Obtaining topographic and derivative images before and after indentation.

Main Results:

• Distinct force-displacement profiles were generated for each material.
• Acetaminophen exhibited a discontinuous loading profile, while others were smooth.
• Rank order of hardness: sucrose > acetaminophen > KCl > sodium stearate.
• Rank order of stiffness: sucrose > KCl > acetaminophen > sodium stearate.

Conclusions:

• Nanoindentation provides unique force-displacement profiles for material characterization.
• The technique successfully differentiated mechanical properties like hardness and stiffness.
• Nanoindentation combined with atomic force microscopy is a promising tool for evaluating materials in pharmaceutical preformulation.