title: The use of in situ near infrared imaging and Raman mapping to study the disproportionation of a drug HCl salt during dissolution.
abstract: NIR imaging and Raman mapping of the dissolution of model pharmaceutical formulations containing the HCl salt of a developmental compound, were carried out using a custom designed flow through cell. The results of this work have shown that NIR imaging and Raman mapping are capable of monitoring the distribution of the components in a formulation during dissolution while also revealing any form changes which may occur in real time. The NIR and Raman data revealed that the drug underwent conversion to the free base when water was used as the dissolution medium. However, in 0.1M HCl this conversion was no longer seen as the medium was below the pHmax (the pH of saturation of both unionised and ionised species and above which the free base can form) of the drug. The data from both approaches broadly agreed demonstrating the applicability of these methods to studying and enhancing our understanding of the complex physical and chemical processes which occur during dissolution in real time.
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Wray
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Sinclair
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Jones
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Clarke
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, New Brunswick, New Jersey 08903, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Both
mesh_terms: D002482:Cellulose / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012492:Salts; D012995:Solubility; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D013607:Tablets
chemical_list: D004364:Pharmaceutical Preparations; D012492:Salts; D013607:Tablets; D002482:Cellulose; C109691:microcrystalline cellulose; D006851:Hydrochloric Acid
keywords: Disproportionation; Dissolution; NIR imaging; Raman mapping