Lisinopril dihydrate: single-crystal x-ray structure and physicochemical characterization of derived solid forms

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Crystallography

Background:

• Lisinopril is a widely used antihypertensive medication.
• Understanding different solid forms (polymorphs, solvates, hydrates) is crucial for drug formulation and bioavailability.
• The commercial form of lisinopril is a dihydrate.

Purpose of the Study:

• To screen for and characterize new solid forms of lisinopril.
• To investigate the physicochemical properties of these new forms, particularly their dissolution rates.
• To determine the single-crystal X-ray structure of lisinopril dihydrate.

Main Methods:

• Recrystallization of lisinopril dihydrate from various solvents.
• Exposure of dehydrated lisinopril to different vapors.
• Powder X-ray diffraction (PXRD) at controlled temperatures.
• Differential scanning calorimetry (DSC) and thermogravimetry (TGA).
• Fourier transform infrared spectroscopy (FTIR).
• Single-crystal X-ray diffraction.

Main Results:

• Identification of new anhydrous and amorphous forms of lisinopril.
• These new forms demonstrated significantly greater intrinsic dissolution rates compared to lisinopril dihydrate.
• The single-crystal X-ray structure of lisinopril dihydrate was determined for the first time.
• The crystal structure revealed the double zwitterionic nature of lisinopril in the solid state.

Conclusions:

• New solid forms of lisinopril with improved dissolution properties were successfully identified.
• The characterization of these forms provides valuable information for potential formulation development.
• The elucidation of the lisinopril dihydrate crystal structure offers fundamental insights into its solid-state behavior.