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dc.contributor.advisorRades, Thomas
dc.contributor.advisorGordon, Keith
dc.contributor.authorTian, Fang
dc.date.available2018-09-02T23:28:00Z
dc.date.copyright2007-05-19
dc.identifier.citationTian, F. (2007, May 19). Towards a deeper understanding of the polymorphic conversion of carbamazepine in aqueous suspension (Thesis, Doctor of Philosophy). Retrieved from http://hdl.handle.net/10523/8314en
dc.identifier.urihttp://hdl.handle.net/10523/8314
dc.description.abstractPolymorphism can influence every aspect of the properties of a solid including the shelf life, dissolution rate, solubility, formulation properties and processing properties of a solid drug. A deeper understanding of polymorphism and related solid state properties would ensure an improved quality of the materials used throughout drug preparation, dosage form formulation and clinical trials. Therefore, determination of the existence of polymorphs and pseudopolymorphs, characterization of different solid state forms and their respective properties, and controlling the existing form in the resulting formulation all form part of a rapidly growing field within pharmaceutical research and industry. Carbamazepine (CBZ) was the model drug used in this study. FT-Raman spectroscopy was chosen as a main investigative technique in this study to evaluate its potential in monitoring (pseudo)polymorphic conversions in aqueous suspensions in the absence or presence of various pharmaceutical excipients. Partial least squares analysis (PLS) was used for quantitative analysis of the spectral data. Earlier it has been found that CBZ converts rapidly to the dihydrate (DH) when exposed to humidity or water, and this has been reported to be the main reason for the sometimes observed greatly decreased bioavailability of marketed CBZ tablets. In this study, the conversion kinetics of CBZ (forms I, II and III) to DH in aqueous suspension were found to be first order kinetics with an unconverted portion (R2 ≥ 0.95), where the crystal morphology appeared to play a more important role in its conversion kinetics than the polymorphic form. The influence of pharmaceutical excipients on the conversion of CBZ in aqueous suspension was also explored. For excipients such as methylcellulose (MC), hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) which have both a low solubility parameter ( < 27.0 MPa1/2) and strong hydrogen bonding groups, complete inhibition of the conversion of CBZ was possible even at a very low concentration (0.1 % w/v). Raman spectroscopy showed its high applicability in investigating CBZ conversion kinetics and screening of excipient effects in aqueous environment. It was demonstrated that Raman has a robust nature in quantitative analysis since problems such as different particle size, morphology, and spatial distribution of the two solid state forms of the drug seemed not to have significant influence on Raman scattering. This study has also clarified the relative importance of many contributing factors (type of crystalline form (CBZ or DH), crystal morphology, surface area, and excipient interactions with drug particles) influencing the in vitro dissolution of CBZ. The solid state characterization approach taken in this study will provide a deeper insight into the dissolution performance of drugs and should thus lead to a better understanding of in vitro/in vivo behavior of drugs.en_NZ
dc.format.mimetypeapplication/pdf
dc.language.isoenen_NZ
dc.publisherUniversity of Otago
dc.titleTowards a deeper understanding of the polymorphic conversion of carbamazepine in aqueous suspensionen_NZ
dc.typeThesisen_NZ
dc.date.updated2018-09-02T23:27:33Z
thesis.degree.disciplinePharmacyen_NZ
thesis.degree.nameDoctor of Philosophyen_NZ
thesis.degree.grantorUniversity of Otagoen_NZ
thesis.degree.levelPhDen_NZ
otago.openaccessOpenen_NZ
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