Midodrine hydro-chloride Form A, C₁₂H₁₉N₂O₄ ⁺·Cl.

Area of Science:

• Crystallography
• Solid-state chemistry
• Computational chemistry

Background:

• Midodrine hydrochloride is a medication used to treat symptomatic orthostatic hypotension.
• Understanding the crystal structure of drug compounds is crucial for pharmaceutical development and formulation.
• Polymorphism in drug compounds can affect bioavailability and stability.

Purpose of the Study:

• To determine the crystal structure of midodrine hydrochloride Form A.
• To characterize the intermolecular interactions within the crystal lattice.
• To provide a structural basis for understanding the physical properties of midodrine hydrochloride Form A.

Main Methods:

• Synchrotron X-ray powder diffraction (XRPD) for crystal structure determination.
• Density functional theory (DFT) for structural optimization.
• Analysis of hydrogen bonding networks and coordination environments.

Main Results:

• Midodrine hydrochloride Form A crystallizes in the monoclinic space group P2₁/c.
• The crystal structure exhibits a layered arrangement perpendicular to the c-axis.
• Extensive hydrogen bonding networks were identified, with chloride anions acting as key acceptors, coordinated by four hydrogen bond donors.

Conclusions:

• The determined crystal structure provides fundamental insights into the solid-state behavior of midodrine hydrochloride Form A.
• The identified hydrogen bonding patterns are critical for stabilizing the crystal lattice.
• This structural information can aid in the development of optimized pharmaceutical formulations and predict potential polymorphic transitions.