Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents

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dc.contributor.advisorCaira, Mino
dc.contributor.advisorBacchi, Alessia
dc.contributor.authorPietrobelli, Erica
dc.date.accessioned2026-08-24T09:54:22Z
dc.date.available2026-08-24T09:54:22Z
dc.date.issued2026
dc.date.updated2026-08-24T09:53:24Z
dc.description.abstractThe objective of this study was to improve the aqueous solubility of four active pharmaceutical ingredients (APIs), namely droperidol, tolfenamic acid, loratadine and 5methoxy-1H-indole-2-carboxylic acid via supramolecular derivatization. The main techniques employed were co-crystallization and cyclodextrin inclusion complexation. All isolated products were characterised using powder X-ray diffraction (PXRD), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). When a single crystal was obtained, it was characterized with single-crystal X-ray diffraction (SCXRD). Co-crystallization was attempted for each API in combination with different “generally recognized as safe” (GRAS) coformers to form co-crystals. Liquid-assisted grinding (LAG) and co-precipitation experiments involving droperidol and loratadine were generally unproductive due to their intractable nature, while tolfenamic acid was tractable but showed no affinity for co-crystallization. On the other hand, the experiments with MICA (5-methoxy-1H-indole-2-carboxylic acid) resulted in the successful synthesis and characterisation of salts with isonicotinamide and piperazine, with a MICA:coformer 2:1 molar ratio in both cases. Cyclodextrin (CD) inclusion complexation of the APIs was studied with β-CD, γ-CD and dimethylated β-CD (DIMEB). The complexation attempts yielded an inclusion complex between DIMEB and loratadine. A single crystal was isolated, and its crystal structure was determined. The general structural features of a new β-CD inclusion complex of MICA were deduced using PXRD in the absence of suitable crystals for SCXRD by establishing isostructurality of its host assembly with that of a series of known CD complexes. Phase solubility studies of MICA were carried out in aqueous medium using β-CD, γ-CD, hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated β-cyclodextrin (RAMEB) and sulfobutyl ether β-cyclodextrin sodium salt (SeβCD). The stability constants of the resulting complexes were estimated, and solubility improvement of MICA was recorded. RAMEB produced the greatest solubility enhancement of MICA by a factor of ~11 at the highest CD concentration employed.
dc.identifier.apacitationPietrobelli, E. (2026). <i>Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents</i>. (). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/43716en_ZA
dc.identifier.chicagocitationPietrobelli, Erica. <i>"Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents."</i> ., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2026. http://hdl.handle.net/11427/43716en_ZA
dc.identifier.citationPietrobelli, E. 2026. Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents. . University of Cape Town ,Faculty of Science ,Department of Chemistry. http://hdl.handle.net/11427/43716en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Pietrobelli, Erica AB - The objective of this study was to improve the aqueous solubility of four active pharmaceutical ingredients (APIs), namely droperidol, tolfenamic acid, loratadine and 5methoxy-1H-indole-2-carboxylic acid via supramolecular derivatization. The main techniques employed were co-crystallization and cyclodextrin inclusion complexation. All isolated products were characterised using powder X-ray diffraction (PXRD), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). When a single crystal was obtained, it was characterized with single-crystal X-ray diffraction (SCXRD). Co-crystallization was attempted for each API in combination with different “generally recognized as safe” (GRAS) coformers to form co-crystals. Liquid-assisted grinding (LAG) and co-precipitation experiments involving droperidol and loratadine were generally unproductive due to their intractable nature, while tolfenamic acid was tractable but showed no affinity for co-crystallization. On the other hand, the experiments with MICA (5-methoxy-1H-indole-2-carboxylic acid) resulted in the successful synthesis and characterisation of salts with isonicotinamide and piperazine, with a MICA:coformer 2:1 molar ratio in both cases. Cyclodextrin (CD) inclusion complexation of the APIs was studied with β-CD, γ-CD and dimethylated β-CD (DIMEB). The complexation attempts yielded an inclusion complex between DIMEB and loratadine. A single crystal was isolated, and its crystal structure was determined. The general structural features of a new β-CD inclusion complex of MICA were deduced using PXRD in the absence of suitable crystals for SCXRD by establishing isostructurality of its host assembly with that of a series of known CD complexes. Phase solubility studies of MICA were carried out in aqueous medium using β-CD, γ-CD, hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated β-cyclodextrin (RAMEB) and sulfobutyl ether β-cyclodextrin sodium salt (SeβCD). The stability constants of the resulting complexes were estimated, and solubility improvement of MICA was recorded. RAMEB produced the greatest solubility enhancement of MICA by a factor of ~11 at the highest CD concentration employed. DA - 2026 DB - OpenUCT DP - University of Cape Town KW - aqueous solubility KW - pharmaceutical ingredients LK - https://open.uct.ac.za PB - University of Cape Town PY - 2026 T1 - Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents TI - Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents UR - http://hdl.handle.net/11427/43716 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/43716
dc.identifier.vancouvercitationPietrobelli E. Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents. []. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2026 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43716en_ZA
dc.language.isoen
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Chemistry
dc.publisher.facultyFaculty of Science
dc.publisher.institutionUniversity of Cape Town
dc.subjectaqueous solubility
dc.subjectpharmaceutical ingredients
dc.titleCrystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents
dc.typeThesis / Dissertation
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMSc
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