Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen

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dc.contributor.advisorCaira, Mino
dc.contributor.authorFr, sler Hannah
dc.date.accessioned2025-02-11T12:37:42Z
dc.date.available2025-02-11T12:37:42Z
dc.date.issued2024
dc.date.updated2025-02-11T12:36:29Z
dc.description.abstractFenbufen and S-(+)-ibuprofen are non-steroidal anti-inflammatory drugs with poor aqueous solubility. In attempts to improve their solubility and bioavailability, crystal engineering techniques were employed to synthesise salts, co-crystals and cyclodextrin inclusion complexes containing these drugs. All newly discovered phases were characterised using single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The synthesis of metal salts of fenbufen containing sodium, potassium, calcium and magnesium ions was attempted. Sodium (Fen-Na+ ) and potassium (Fen-K + ) salts were successfully synthesised and characterised, the former also being successfully characterised by SCXRD. Using Fen-Na+ as a potential ‘guest', the syntheses of inclusion complexes with β-cyclodextrin (BCD) and γ-cyclodextrin (GCD) were attempted. The resulting complexes, BCD∙Fen-Na+ , and GCD∙Fen-Na+ , were successfully synthesised and characterised and were shown to have 1:1 cyclodextrin-salt compositions. Solubility studies of all salts and cyclodextrin inclusion complexes reported in this dissertation were performed in both aqueous and Fasted State Simulated Intestinal Fluid (pH 6.5) media. Phase solubility studies of fenbufen were carried out using hydroxypropyl β-cyclodextrin (HPBCD), randomly methylated β-cyclodextrin (RAMEB), γ-cyclodextrin (GCD) and sulfobutyl ether βcyclodextrin sodium (SBEBCD). RAMEB effected the greatest solubility enhancement of fenbufen by a factor of ~200 at the highest CD concentration employed. Liquid-assisted grinding (LAG) and co-precipitation experiments involving fenbufen and watersoluble coformers resulted in the successful synthesis and full characterisation of an ionic co-crystal consisting of fenbufen and isonicotinamide (FEN-ISN) with 2:3 stoichiometry. Salts of S-(+)-ibuprofen with the antifibrinolytic agents 6-aminocaproic acid [(S-IBU)- (ACA)+ ] and tranexamic acid [(S-IBU)- (TXA)+ ] were successfully synthesised and comprehensively characterised. A second crystalline form of a cyclodextrin inclusion complex between S-IBU and heptakis(2,6-diO-methyl)-β-cyclodextrin (DMB∙S-IBU) was discovered. All new phases, (S-IBU)- (ACA)+ , (S-IBU)- (TXA)+ and DMB∙S-IBU, were found to occur with 1:1 stoichiometry.
dc.identifier.apacitationFr, s. H. (2024). <i>Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen</i>. (). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/40917en_ZA
dc.identifier.chicagocitationFr, sler Hannah. <i>"Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen."</i> ., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2024. http://hdl.handle.net/11427/40917en_ZA
dc.identifier.citationFr, s.H. 2024. Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen. . University of Cape Town ,Faculty of Science ,Department of Chemistry. http://hdl.handle.net/11427/40917en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Fr, sler Hannah AB - Fenbufen and S-(+)-ibuprofen are non-steroidal anti-inflammatory drugs with poor aqueous solubility. In attempts to improve their solubility and bioavailability, crystal engineering techniques were employed to synthesise salts, co-crystals and cyclodextrin inclusion complexes containing these drugs. All newly discovered phases were characterised using single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The synthesis of metal salts of fenbufen containing sodium, potassium, calcium and magnesium ions was attempted. Sodium (Fen-Na+ ) and potassium (Fen-K + ) salts were successfully synthesised and characterised, the former also being successfully characterised by SCXRD. Using Fen-Na+ as a potential ‘guest', the syntheses of inclusion complexes with β-cyclodextrin (BCD) and γ-cyclodextrin (GCD) were attempted. The resulting complexes, BCD∙Fen-Na+ , and GCD∙Fen-Na+ , were successfully synthesised and characterised and were shown to have 1:1 cyclodextrin-salt compositions. Solubility studies of all salts and cyclodextrin inclusion complexes reported in this dissertation were performed in both aqueous and Fasted State Simulated Intestinal Fluid (pH 6.5) media. Phase solubility studies of fenbufen were carried out using hydroxypropyl β-cyclodextrin (HPBCD), randomly methylated β-cyclodextrin (RAMEB), γ-cyclodextrin (GCD) and sulfobutyl ether βcyclodextrin sodium (SBEBCD). RAMEB effected the greatest solubility enhancement of fenbufen by a factor of ~200 at the highest CD concentration employed. Liquid-assisted grinding (LAG) and co-precipitation experiments involving fenbufen and watersoluble coformers resulted in the successful synthesis and full characterisation of an ionic co-crystal consisting of fenbufen and isonicotinamide (FEN-ISN) with 2:3 stoichiometry. Salts of S-(+)-ibuprofen with the antifibrinolytic agents 6-aminocaproic acid [(S-IBU)- (ACA)+ ] and tranexamic acid [(S-IBU)- (TXA)+ ] were successfully synthesised and comprehensively characterised. A second crystalline form of a cyclodextrin inclusion complex between S-IBU and heptakis(2,6-diO-methyl)-β-cyclodextrin (DMB∙S-IBU) was discovered. All new phases, (S-IBU)- (ACA)+ , (S-IBU)- (TXA)+ and DMB∙S-IBU, were found to occur with 1:1 stoichiometry. DA - 2024 DB - OpenUCT DP - University of Cape Town KW - Chemistry LK - https://open.uct.ac.za PB - University of Cape Town PY - 2024 T1 - Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen TI - Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen UR - http://hdl.handle.net/11427/40917 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/40917
dc.identifier.vancouvercitationFr sH. Synthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen. []. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2024 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/40917en_ZA
dc.language.rfc3066Eng
dc.publisher.departmentDepartment of Chemistry
dc.publisher.facultyFaculty of Science
dc.publisher.institutionUniversity of Cape Town
dc.subjectChemistry
dc.titleSynthesis and characterisation of new multi-component compounds containing the non-steroidal anti-inflammatory drugs fenbufen and S(+)-ibuprofen
dc.typeThesis / Dissertation
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMSc
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