title: Correlation of Phosphorus Cross-Linking to Hydration Rates in Sodium Starch Glycolate Tablet Disintegrants Using MRI.
abstract: Understanding the behavior of tablet disintegrants is valuable in the development of pharmaceutical solid dosage formulations. In this study, high-resolution magnetic resonance imaging has been used to understand the hydration behavior of a series of commercial sodium starch glycolate (SSG) samples, providing robust estimates of tablet disintegration rate that could be correlated with physicochemical properties of the SSGs, such as the extent of phosphorus (P) cross-linking as obtained from infra-red spectroscopy. Furthermore, elemental analysis together with powder X-ray diffraction has been used to quantify the presence of carboxymethyl groups and salt impurities, which also contribute to the disintegration behavior. The utility of Fast Low Angle SHot magnetic resonance imaging has been demonstrated as an approach to rapidly acquire approximations of the volume of a disintegrating tablet and, together with a robust voxel analysis routine, extract tablet disintegration rates. In this manner, a complete characterization of a series of SSG grades from different sources has been performed, showing the variability in their physicochemical properties and demonstrating a correlation between their disintegration rates and intrinsic characteristics. The insights obtained will be a valuable aid in the choice of disintegrant source as well as in managing SSG variability to ensure robustness of drug products containing SSG.
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903. Electronic address: anuji.abraham@bms.com.
authors.forename: Anuji
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903.
authors.forename: Dolapo
authors.initials: D
authors.lastname: Olusanmi
authors.affiliation: Department of Chemistry, New York University, New York, New York 10003.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ilott
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903.
authors.forename: David
authors.initials: D
authors.lastname: Good
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903.
authors.forename: Denette
authors.initials: D
authors.lastname: Murphy
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mcnamara
authors.affiliation: Department of Chemistry, New York University, New York, New York 10003.
authors.forename: Alexej
authors.initials: A
authors.lastname: Jerschow
authors.affiliation: Bristol-Myers Squibb, Materials Science and Engineering, Drug Product Science and Technology, New Brunswick, New Jersey 08903.
authors.forename: Rao V
authors.initials: RV
authors.lastname: Mantri
mesh_terms: D003432:Cross-Linking Reagents / Q000032:analysis* / Q000378:metabolism; D005079:Excipients / Q000032:analysis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010758:Phosphorus / Q000032:analysis* / Q000378:metabolism; D012995:Solubility; D013055:Spectrophotometry, Infrared / Q000379:methods; D013213:Starch / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D013607:Tablets; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D003432:Cross-Linking Reagents; D005079:Excipients; D013607:Tablets; D010758:Phosphorus; D013213:Starch; C048390:sodium starch glycolate
keywords: FLASH MRI; disintegrants; imaging methods; infra-red spectroscopy; sodium starch glycolate; tablet disintegration; tablet imaging