Reactivity differences of indomethacin solid forms with ammonia gas.

Area of Science:

• Solid-state chemistry
• Pharmaceutical science
• Materials science

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin exist in various solid-state forms.
• Understanding the reactivity of these forms is crucial for drug formulation and stability.

Purpose of the Study:

• To investigate the acid-base reaction of different solid-state forms of indomethacin with ammonia gas.
• To elucidate the relationship between crystal structure, molecular arrangement, and reactivity.

Main Methods:

• X-ray powder diffraction
• Optical microscopy
• Gravimetry
• Spectroscopic methods

Main Results:

• Amorphous indomethacin reacts readily with ammonia gas to form an amorphous ammonium salt.
• The metastable alpha-form reacts to yield a microcrystalline ammonium salt, with anisotropic propagation along the a-axis.
• The stable gamma-form is inert to ammonia gas due to its crystal structure.

Conclusions:

• Reactivity of indomethacin solid forms with ammonia gas is dependent on molecular arrangement, not packing density.
• The exposed carboxylic acid groups in the alpha-form facilitate reaction, while they are shielded in the gamma-form.