This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:720781 |
| Date | January 2008 |
| Creators | Ibrahim Mohamed, Asim Yousif |
| Publisher | University of Bradford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10454/12760 |
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