Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Computational Chemistry

Background:

• Clopidogrel hydrogensulfate (HSCL) is a globally significant antiplatelet medication.
• Ensuring the correct polymorphic form in solid dosage forms is critical for drug efficacy and stability.
• Existing methods for polymorph verification may lack speed or convenience for routine analysis.

Purpose of the Study:

• To develop and validate a rapid and convenient method for identifying clopidogrel hydrogensulfate (HSCL) polymorphs in solid dosage forms.
• To provide a reliable tool for quality control in pharmaceutical manufacturing.
• To support the development of new HSCL-containing pharmaceutical products and combat counterfeit drugs.

Main Methods:

• Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy was employed for structural analysis.
• Ab initio gauge-including projector-augmented wave (GIPAW) calculations were used to determine NMR shielding constants.
• The methodology was validated using commercially available solid dosage forms of HSCL.

Main Results:

• A rapid and convenient method for polymorph verification of HSCL was successfully established.
• The combined approach of solid-state NMR and computational calculations accurately identifies HSCL polymorphs.
• The method is applicable to existing commercial solid dosage forms.

Conclusions:

• The developed methodology offers an effective means for identifying clopidogrel hydrogensulfate (HSCL) polymorphs in pharmaceutical products.
• This technique is valuable for pharmaceutical development, quality assurance, and the detection of counterfeit medications.
• Solid-state NMR spectroscopy coupled with theoretical calculations provides robust structural characterization for HSCL.