title: Characterization of cromolyn sodium hydrates and its formulation by (23) Na-multiquantum and magic-angle spinning nuclear magnetic resonance spectroscopy.
abstract: We characterized cromolyn sodium (CS) hydrates and evaluated their molecular states in low-dose formulations using Na-multiquantum magic-angle spinning (MQMAS) nuclear magnetic resonance (NMR) analysis. Two CS hydrates, low-water-content hydrated form and high-water-content hydrated form containing 2-3 and 5-6 hydrates, respectively, were prepared by humidification. Single-crystal X-ray diffraction and powder X-ray diffraction analysis revealed that these CS hydrates contained sodium channel structures and that water molecules were adsorbed on the sodium nucleus. (13) C-cross-polarization/MAS NMR spectra of these hydrates revealed similar results, confirming that the water molecules were adsorbed not on the cromolyn skeletons but mainly on the sodium nucleus. In contrast, (23) Na-MQMAS NMR analysis allowed us to clearly distinguish these hydrates without discernible effects from quadrupolar interaction. Thus, MQMAS NMR analysis is a valuable tool for evaluating salt drugs and their formulations.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Umino
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.forename: Hyuma
authors.initials: H
authors.lastname: Masu
authors.forename: Waree
authors.initials: W
authors.lastname: Limwikrant
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
mesh_terms: D018927:Anti-Asthmatic Agents / Q000737:chemistry*; D004205:Cromolyn Sodium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D012964:Sodium / Q000032:analysis; D014867:Water / Q000737:chemistry*
chemical_list: D018927:Anti-Asthmatic Agents; D014867:Water; D012964:Sodium; D004205:Cromolyn Sodium
keywords: MQMAS NMR; X-ray diffractometry; cromolyn sodium; crystallography; hydrates; solid state NMR; water sorption