Surface crystallization of indomethacin below Tg

Area of Science:

• Solid-state chemistry
• Materials science
• Pharmaceutical sciences

Background:

• Indomethacin (IMC) is a widely used non-steroidal anti-inflammatory drug.
• Understanding the crystallization behavior of amorphous drugs is crucial for formulation stability and bioavailability.
• Surface crystallization phenomena can significantly influence the overall transformation kinetics of amorphous materials.

Purpose of the Study:

• To investigate the surface crystallization of indomethacin (IMC) below its glass transition temperature (T(g)).
• To elucidate the impact of surface crystallization on the overall crystallization kinetics of amorphous IMC.
• To differentiate surface crystallization from bulk crystallization processes.

Main Methods:

• Crystal growth rates were measured in liquid layers under different conditions (cover glass in place vs. removed).
• Polymorph identification utilized powder X-ray diffraction, Raman microscopy, and hot-stage microscopy.
• Amorphous IMC particles were stored at 40°C and analyzed over time using differential scanning calorimetry (DSC).

Main Results:

• Surface crystallization of IMC below T(g) was approximately two orders of magnitude faster than bulk crystallization.
• A distinct surface crystalline layer formed, surrounding a slower-crystallizing interior.
• Surface crystallization predominantly yielded the gamma polymorph of IMC.
• Amorphous IMC powders exhibited rapid initial crystallization that abruptly slowed at "saturation levels," influenced by particle size.

Conclusions:

• Faster surface crystallization kinetics compared to bulk crystallization result in unique overall crystallization behavior.
• The observed phenomenon involves an initial rapid increase in crystallinity followed by a significant slowdown.
• Distinguishing between surface and bulk crystallization is essential for accurate modeling and effective control of amorphous solid crystallization.