The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension
Authors: Tian, Fang1; Saville, Dorothy J.1; Gordon, Keith C.2; Strachan, Clare J.3; Zeitler, J. Axel1; Sandler, Niklas1; Rades, Thomas1
Source: Journal of Pharmacy and Pharmacology, Volume 59, Number 2, February 2007 , pp. 193-201(9)
Publisher: Pharmaceutical Press
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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 MPa1/2) 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 MPa1/2). 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.Document Type: Research article
DOI: 10.1211/jpp.59.2.0006
Affiliations: 1: School of Pharmacy, University of Otago, Dunedin, New Zealand 2: Department of Chemistry, University of Otago, Dunedin, New Zealand 3: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland
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