title: The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension.
abstract: The influence of various excipients on the conversion of carbamazepine polymorphs to the dihydrate in aqueous suspension has been investigated. Ten excipients having functional groups which were potentially able to form hydrogen bonds with carbamazepine (group 1: methylcellulose, hypromellose (hydroxypropyl methylcellulose), hydroxypropylcellulose (HPC), 2-hydroxyethylcellulose (HEC), carmellose sodium (sodium carboxymethylcellulose), cellobiose; group 2: povidone (polyvinylpyrrolidone), povidone-vinyl acetate copolymer (povidone/VA) and N-methyl-2-pyrrolidone; group 3: macrogol (polyethylene glycol) and polyethylene oxide-polypropylene oxide copolymer (PEO/PPO)) were selected. Carbamazepine polymorphic forms III and I were dispersed separately into each aqueous excipient solution (0.1%, w/v) for 30 min at room temperature. The inhibition effect of each excipient was quantified using Raman spectroscopy combined with multivariate analyses. The solubility parameter of each excipient was calculated and used for categorizing excipients. Excipients in groups 1 and 2, which had both low solubility parameters (< 27.0 MPa(1/2)) and strong hydrogen bonding groups, inhibited the conversion completely. With increasing solubility parameter, the inhibition effect decreased for group 1 excipients, especially for carbamazepine form I, which had a higher specific surface area. Also, the excipients of group 3, lacking strong hydrogen bonding groups, showed poor inhibition although they had low solubility parameters (< 21.0 MPa(1/2)). This study indicated the importance of both hydrogen bonding interaction and a suitable hydrophobicity (expressed by the solubility parameter) in the inhibition of the conversion of carbamazepine to the dihydrate.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Saville
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.forename: J Axel
authors.initials: JA
authors.lastname: Zeitler
authors.forename: Niklas
authors.initials: N
authors.lastname: Sandler
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D002220:Carbamazepine / Q000032:analysis / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D044367:Phase Transition; D033362:Powder Diffraction; D013059:Spectrum Analysis, Raman; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D013535:Suspensions; D002220:Carbamazepine