Application of 13C CPMAS NMR for Qualitative and Quantitative Characterization of Carvedilol and its Commercial Formulations

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 5; pp. 1763 - 1772
• Main Authors: Zielińska-pisklak, Monika, Pisklak, Dariusz Maciej, Wawer, Iwona
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.05.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Adrenergic beta-Antagonists - analysis; Biological and medical sciences; Carbazoles - analysis; Carbon Isotopes; Chemistry, Pharmaceutical; excipients; formulation; General pharmacology; Magnetic Resonance Spectroscopy - methods; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propanolamines - analysis; solid dosage form; solid-state NMR; tablet; formulation; tablet; solid-state NMR; excipients; solid dosage form; Pharmaceutical technology; Vasodilator agent; Vehicle(excipient); α1-Adrenergic receptor; β2-Adrenergic receptor; Characterization; Solid state; Alpha blocking agent; β1-Adrenergic receptor; Carvedilol; Formulation; Dosage form; Antihypertensive agent; Solid form; Tablet; Antagonist; Beta blocking agent; Quantitative analysis
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23062

13C cross-polarization magic-angle spinning nuclear magnetic resonance (CPMAS NMR) spectroscopy was applied to the identification and characterization of carvedilol (1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)-ethylamino]-propan-2-ol) in pharmaceutical preparations. Solid-state spectra (standard linewidth and lack of signal multiplicity) of carvedilol indicate that its physical form is the same (freebase form II); no other polymorphic forms were detected. The spectra of excipients, recorded under the same conditions, were helpful in their identification. The differences in chemical shifts for tablets I–VI are insignificant and suggest that there are no strong intermolecular drug–excipient interactions. The drugs from six manufacturers contained the same amount (25mg) of the active substance per tablet; however, tablets differ in size and thus in the concentration of carvedilol. An attempt at quantitation of carvedilol in the dosage forms was made. The cross-polarization kinetics and other measurement parameters affecting the intensity and reproducibility of the spectra were determined. The results revealed a satisfying relationship between the composition of the tablets and the intensity of selected NMR signals. The 13C CPMAS NMR technique was found to provide accurate quantification of drugs without any chemical preparation, as shown by the particular case of carvedilol's solid formulations.