Quantifying Disproportionation in Pharmaceutical Formulations with 35Cl Solid-State NMR.
David A Hirsh1, Yongchao Su2, Haichen Nie2
1Department of Chemistry & Biochemistry , University of Windsor , Windsor , ON , N9B 3P4 , Canada.
Molecular Pharmaceutics
|July 18, 2018
Summary
Ultra-wideline 35Cl solid-state NMR (SSNMR) accurately detects pioglitazone HCl disproportionation in drug formulations. This method quantifies changes in solid dosage forms, offering insights into drug stability.
Area of Science:
- Analytical Chemistry
- Solid-State Chemistry
- Pharmaceutical Analysis
Background:
- Characterizing drug substances is vital for stability and bioavailability assessments in diverse formulations.
- Drug formulations, especially ionic salts like pioglitazone HCl, can undergo disproportionation under stress conditions (heat, humidity), altering properties.
- Solid dosage forms present challenges for analysis due to their complex heterogeneous mixtures of active pharmaceutical ingredients (APIs) and excipients.
Purpose of the Study:
- To demonstrate the utility of ultra-wideline 35Cl solid-state NMR (UW 35Cl SSNMR) for characterizing the disproportionation of pioglitazone HCl (PiogHCl) in pharmaceutical formulations.
- To quantitatively assess the degree of PiogHCl disproportionation in stressed solid dosage forms.
- To highlight the advantages of 35Cl SSNMR in directly probing chloride anions without interference from excipients.
Main Methods:
- Utilized ultra-wideline 35Cl solid-state NMR (UW 35Cl SSNMR) spectroscopy.
- Prepared and stressed pioglitazone HCl (PiogHCl) mixtures with metallic stearate excipients under elevated temperature and humidity.
- Quantitatively analyzed samples to determine the extent of PiogHCl disproportionation.
Main Results:
- UW 35Cl SSNMR accurately quantified PiogHCl in mixed samples with a precision of ±1 wt %.
- The method successfully measured the degree of PiogHCl disproportionation in formulation samples subjected to stress conditions.
- 35Cl SSNMR directly detected all chlorine-containing species, including intact PiogHCl and disproportionation products, without interference from excipients.
Conclusions:
- UW 35Cl SSNMR is a reliable and quantitative method for characterizing the disproportionation of pioglitazone HCl in solid dosage formulations.
- This technique offers a direct and specific way to monitor chemical changes in complex pharmaceutical mixtures.
- The findings demonstrate the potential of 35Cl SSNMR for drug stability studies and quality control in pharmaceutical development.
Keywords:
chlorine-35disproportionationdosage formulationshydrochloride saltsprocessing-induced phase transitionsquantificationsolid-state NMRMore Related Videos
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