title: Influence of polymeric excipient properties on crystal hydrate formation kinetics of caffeine in aqueous slurries.
abstract: The influence of polymeric excipients on the hydrate transformation of caffeine (CAF) was studied. Anhydrous CAF was added to aqueous solutions containing different additives and the transformation to the hydrate form was monitored using in-line Raman spectroscopy. Various properties of two known inhibitors of CAF hydrate formation, polyacrylic acid (PAA) and polyvinyl alcohol (PVA), were investigated. For inhibition by PAA, a pH dependence was observed: at low pH, the inhibition was greatest, whereas no inhibitory effects were observed at pH above 6.5. For PVA, grades with high percent hydrolysis were the most effective at inhibiting the transformation. In addition, PVA with higher molecular weight showed slightly more inhibition than the shorter chain PVA polymers. A variety of other hydroxyl containing compounds were examined but none inhibited the CAF anhydrate-to-hydrate transformation. The observed inhibitory effects of PAA and PVA are attributed to the large number of closely spaced hydrogen bond donating groups of the polymer molecule, which can interact with the CAF hydrate crystal.
authors.affiliation: Department of Chemistry, University of Nebraska at Omaha, Omaha, Nebraska 68182, USA. agift@unomaha.edu
authors.forename: Alan D
authors.initials: AD
authors.lastname: Gift
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Southard
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Riesberg
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D002110:Caffeine / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D014867:Water / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D005079:Excipients; D014867:Water; D002110:Caffeine; C006903:carbopol 940; D011142:Polyvinyl Alcohol