Solid state characterization and crystal structure from X-ray powder diffraction of two polymorphic forms of...

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Ranitidine hydrochloride (RAN-HCl) is a widely used anti-ulcer medication.
• The solid-state properties of ranitidine base (RAN-B), a precursor to RAN-HCl, are less understood.
• Polymorphism significantly impacts drug stability, solubility, and bioavailability.

Purpose of the Study:

• To conduct a comprehensive solid-state characterization of RAN-B polymorphs.
• To determine and compare the crystal structures of RAN-B form I and form II.
• To elucidate the intermolecular interactions and packing arrangements in RAN-B polymorphs.

Main Methods:

• Utilized microscopy, thermal analysis, FTIR, (13)C-CPMAS-NMR, and X-ray powder diffraction for solid-state characterization.
• Determined crystal structures using X-ray powder diffraction with simulated annealing and whole profile pattern matching.
• Refined crystal structures via rigid-body Rietveld refinement.

Main Results:

• Identified and characterized two distinct polymorphs of RAN-B: form I (monoclinic) and form II (orthorhombic).
• Determined the precise cell parameters and space groups for both RAN-B form I (P2(1)/c) and form II (Pbca).
• Observed intramolecular hydrogen bonding involving the nitro group, leading to a Z configuration, and identified a tail-to-tail packing motif.

Conclusions:

• RAN-B exhibits monotropic polymorphism, with distinct crystal structures and packing compared to RAN-HCl.
• The solid-state characterization provides fundamental data for understanding RAN-B's physical properties.
• Insights into RAN-B polymorphism are essential for pharmaceutical development and formulation.