title: Quantitation of crystalline and amorphous forms of anhydrous neotame using 13C CPMAS NMR spectroscopy.
abstract: Although most drugs are formulated in the crystalline state, amorphous or other crystalline forms are often generated during the formulation process. The presence of other forms can dramatically affect the physical and chemical stability of the drug. The identification and quantitation of different forms of a drug is a significant analytical challenge, especially in a formulated product. The ability of solid-state 13C NMR spectroscopy with cross polarization (CP) and magic-angle spinning (MAS) to quantify the amounts of three of the multiple crystalline and amorphous forms of the artificial sweetener neotame is described. It was possible to quantify, in a mixture of two anhydrous polymorphic forms of neotame, the amount of each polymorph within 1-2%. In mixtures of amorphous and crystalline forms of neotame, the amorphous content could be determined within 5%. It was found that the crystalline standards that were used to prepare the mixtures were not pure crystalline forms, but rather a mixture of crystalline and amorphous forms. The effect of amorphous content in the crystalline standards on the overall quantitation of the two crystalline polymorphic forms is discussed. The importance of differences in relaxation parameters and CP efficiencies on quantifying mixtures of different forms using solid-state NMR spectroscopy is also addressed.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Avenue, Lawrence, Kansas 66047, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Offerdahl
authors.forename: Jonathon S
authors.initials: JS
authors.lastname: Salsbury
authors.forename: Zedong
authors.initials: Z
authors.lastname: Dong
authors.forename: David J W
authors.initials: DJ
authors.lastname: Grant
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Schroeder
authors.forename: Indra
authors.initials: I
authors.lastname: Prakash
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gorman
authors.forename: Dewey H
authors.initials: DH
authors.lastname: Barich
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Munson
mesh_terms: D002152:Calorimetry, Differential Scanning; D002247:Carbon Isotopes; D003460:Crystallization; D004151:Dipeptides / Q000032:analysis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013549:Sweetening Agents / Q000032:analysis* / Q000737:chemistry
chemical_list: D002247:Carbon Isotopes; D004151:Dipeptides; D013549:Sweetening Agents; C404525:neotame