Quantifying Pharmaceutical Formulations from Proton Detected Solid-State NMR under Ultrafast Magic Angle Spinning.

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Materials Science

Background:

• Assessing physicochemical stability of active pharmaceutical ingredients in solid dosages is crucial.
• Challenges exist in quantifying phase stability and low drug content in complex formulations using routine methods.
• Proton-detected solid-state NMR (ssNMR) with ultrafast magic angle spinning (UF-MAS) offers enhanced resolution and sensitivity.

Purpose of the Study:

• To demonstrate the application of 60 kHz UF-MAS ssNMR for quantifying pioglitazone free base (PIO-FB) in binary and multicomponent pharmaceutical systems.
• To establish the limit of detection for PIO-FB in the presence of its hydrochloride salt (PIO-HCl).
• To showcase the capability of 2D 1H-1H ssNMR for analyzing complex formulations.

Main Methods:

• Implementation of 60 kHz UF-MAS proton-detected ssNMR.
• Utilized one-dimensional 1H ssNMR to differentiate pioglitazone free base and its hydrochloride salt.
• Employed two-dimensional 1H-1H correlation ssNMR for complex mixture analysis.

Main Results:

• One-dimensional 1H ssNMR successfully differentiated PIO-FB from PIO-HCl with a limit of detection at 1.77% (w/w).
• Two-dimensional 1H-1H ssNMR quantified approximately 2.0% (w/w) PIO-FB in a multicomponent formulation.
• The 1H ssNMR method provided higher resolution and faster acquisition compared to conventional 13C techniques.

Conclusions:

• 60 kHz UF-MAS 1H ssNMR is a powerful and novel method for quantifying drug substances in solid dosages.
• This technique addresses the limitations of conventional methods for analyzing low drug loading and multicomponent formulations.
• UF-MAS ssNMR enhances the understanding of pharmaceutical material stability and quality control.