{"id":{"repo_id":"de-montfort","oai_identifier":"oai:dora.dmu.ac.uk:2086/21127"},"canonical_url":"https://search.dev.ndltd.org/etd/de-montfort/oai:dora.dmu.ac.uk:2086/21127","repository":{"repo_id":"de-montfort","name":"De Montfort University","base_url":"https://dora.dmu.ac.uk/server/oai/request"},"display":{"title":"Mechanistic Understanding of Co-crystal solubility and dissolution by using a combination of Experimental and Molecular Modelling Techniques","abstract":"The purpose of this study is to improve the solubility, dissolution rate and permeability of poorly water-soluble drugs by understanding the mechanism of dissolution at molecular level of Flufenamic acid and Carbamazepine co-crystals in the presence of polymers. This study has been separated into four sections: (1) Formation of pharmaceutical co-crystals: Three pharmaceutical co-crystals of poorly water soluble active pharmaceutical ingredient (API) of Flufenamic acid (FFA) and Carbamazepine (CBZ) were synthesized, including 1:1 Flufenamic acid-theophylline co-crystal (FFATP CO), 1:1 Flufenamic acid-nicotinamide co-crystal (FFA-NIC CO) and 1:1 Carbamazepine-nicotinamide co-crystal (CBZ-NIC CO). The results of Fourier Transform Infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray Powder Diffraction (XRPD) confirmed the formation of co-crystals. (2) The effect of polymers on the surface dissolution of co-crystals: The influence of three polymers (polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2- pyrrolidone (60%) and vinyl acetate (40%) (PVP-VA)) on the surfaces of FFA-TP CO, FFA-NIC CO and CBZ-NIC CO was studied using Atomic force Microscopy (AFM), Scanning electron microscopy (SEM) and Raman spectroscopy. It was found that the co-crystals have different dissolution mechanisms, and that addition of polymers can alter the dissolution properties of co-crystals by interacting with the crystal faces. (3) The molecular interactions between the drugs, co-formers and polymers were investigated using Nuclear Magnetic Resonance (NMR) and Diffusion Ordered Spectroscopy (DOSY). It was found that the type of a polymer, its concentration, and the interaction of the polymer with a co-former in solution will significantly affect the FFA and CBZ co-crystals (4). Molecular modelling of free drug molecules with coformers and polymers in the presence of water molecules: Results indicate bulk precipitation could be occurring for FFA molecules in solution and that PVP-VA was an effective precipitation inhibitor for all three co-crystals studied in solution. Overall, PVP was an effective polymer for surface precipitation inhibitor and PVP-VA was the most effective inhibitor for precipitation in solution.","abstract_html":"The purpose of this study is to improve the solubility, dissolution rate and permeability of poorly water-soluble drugs by understanding the mechanism of dissolution at molecular level of Flufenamic acid and Carbamazepine co-crystals in the presence of polymers. This study has been separated into four sections: (1) Formation of pharmaceutical co-crystals: Three pharmaceutical co-crystals of poorly water soluble active pharmaceutical ingredient (API) of Flufenamic acid (FFA) and Carbamazepine (CBZ) were synthesized, including 1:1 Flufenamic acid-theophylline co-crystal (FFATP CO), 1:1 Flufenamic acid-nicotinamide co-crystal (FFA-NIC CO) and 1:1 Carbamazepine-nicotinamide co-crystal (CBZ-NIC CO). The results of Fourier Transform Infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray Powder Diffraction (XRPD) confirmed the formation of co-crystals. (2) The effect of polymers on the surface dissolution of co-crystals: The influence of three polymers (polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2- pyrrolidone (60%) and vinyl acetate (40%) (PVP-VA)) on the surfaces of FFA-TP CO, FFA-NIC CO and CBZ-NIC CO was studied using Atomic force Microscopy (AFM), Scanning electron microscopy (SEM) and Raman spectroscopy. It was found that the co-crystals have different dissolution mechanisms, and that addition of polymers can alter the dissolution properties of co-crystals by interacting with the crystal faces. (3) The molecular interactions between the drugs, co-formers and polymers were investigated using Nuclear Magnetic Resonance (NMR) and Diffusion Ordered Spectroscopy (DOSY). It was found that the type of a polymer, its concentration, and the interaction of the polymer with a co-former in solution will significantly affect the FFA and CBZ co-crystals (4). Molecular modelling of free drug molecules with coformers and polymers in the presence of water molecules: Results indicate bulk precipitation could be occurring for FFA molecules in solution and that PVP-VA was an effective precipitation inhibitor for all three co-crystals studied in solution. Overall, PVP was an effective polymer for surface precipitation inhibitor and PVP-VA was the most effective inhibitor for precipitation in solution.","abstract_has_math":false,"creators":["Kirubakaran, Preyanthiny"],"institution":"De Montfort University","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-01","date_published":"2021-01","updated_at":"2026-07-24T06:18:29Z","subjects":[],"languages":[],"rights":[],"rights_urls":["https://dora.dmu.ac.uk/bitstreams/be963c5c-f5ab-407a-8f19-19064d8593fa/download"],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Kirubakaran, Preyanthiny"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2021-01"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Faculty of Health and Life Sciences"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["De Montfort University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://dora.dmu.ac.uk/handle/2086/21127"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or dissertation"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["https://dora.dmu.ac.uk/bitstreams/be963c5c-f5ab-407a-8f19-19064d8593fa/download"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://dora.dmu.ac.uk/bitstreams/54b8f9be-05c4-4c4e-9714-5dfe0d54898d/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The purpose of this study is to improve the solubility, dissolution rate and permeability of poorly water-soluble drugs by understanding the mechanism of dissolution at molecular level of Flufenamic acid and Carbamazepine co-crystals in the presence of polymers. This study has been separated into four sections: (1) Formation of pharmaceutical co-crystals: Three pharmaceutical co-crystals of poorly water soluble active pharmaceutical ingredient (API) of Flufenamic acid (FFA) and Carbamazepine (CBZ) were synthesized, including 1:1 Flufenamic acid-theophylline co-crystal (FFATP CO), 1:1 Flufenamic acid-nicotinamide co-crystal (FFA-NIC CO) and 1:1 Carbamazepine-nicotinamide co-crystal (CBZ-NIC CO). The results of Fourier Transform Infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray Powder Diffraction (XRPD) confirmed the formation of co-crystals. (2) The effect of polymers on the surface dissolution of co-crystals: The influence of three polymers (polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2- pyrrolidone (60%) and vinyl acetate (40%) (PVP-VA)) on the surfaces of FFA-TP CO, FFA-NIC CO and CBZ-NIC CO was studied using Atomic force Microscopy (AFM), Scanning electron microscopy (SEM) and Raman spectroscopy. It was found that the co-crystals have different dissolution mechanisms, and that addition of polymers can alter the dissolution properties of co-crystals by interacting with the crystal faces. (3) The molecular interactions between the drugs, co-formers and polymers were investigated using Nuclear Magnetic Resonance (NMR) and Diffusion Ordered Spectroscopy (DOSY). It was found that the type of a polymer, its concentration, and the interaction of the polymer with a co-former in solution will significantly affect the FFA and CBZ co-crystals (4). Molecular modelling of free drug molecules with coformers and polymers in the presence of water molecules: Results indicate bulk precipitation could be occurring for FFA molecules in solution and that PVP-VA was an effective precipitation inhibitor for all three co-crystals studied in solution. Overall, PVP was an effective polymer for surface precipitation inhibitor and PVP-VA was the most effective inhibitor for precipitation in solution."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["957ce5e37996841c062039318170ac7f","bd41181d9a4c38b5ebacc69a027024d9","b0312873b14c252d42d32e0a5631e92e"]},{"key":"dc:title","label":"Title","values":["Mechanistic Understanding of Co-crystal solubility and dissolution by using a combination of Experimental and Molecular Modelling Techniques"]}]}],"canonical_facts":{"dc:creator":["Kirubakaran, Preyanthiny"],"dc:date.issued":["2021-01"],"dc:description.abstract":["The purpose of this study is to improve the solubility, dissolution rate and permeability of poorly water-soluble drugs by understanding the mechanism of dissolution at molecular level of Flufenamic acid and Carbamazepine co-crystals in the presence of polymers. 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(2) The effect of polymers on the surface dissolution of co-crystals: The influence of three polymers (polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2- pyrrolidone (60%) and vinyl acetate (40%) (PVP-VA)) on the surfaces of FFA-TP CO, FFA-NIC CO and CBZ-NIC CO was studied using Atomic force Microscopy (AFM), Scanning electron microscopy (SEM) and Raman spectroscopy. It was found that the co-crystals have different dissolution mechanisms, and that addition of polymers can alter the dissolution properties of co-crystals by interacting with the crystal faces. (3) The molecular interactions between the drugs, co-formers and polymers were investigated using Nuclear Magnetic Resonance (NMR) and Diffusion Ordered Spectroscopy (DOSY). It was found that the type of a polymer, its concentration, and the interaction of the polymer with a co-former in solution will significantly affect the FFA and CBZ co-crystals (4). Molecular modelling of free drug molecules with coformers and polymers in the presence of water molecules: Results indicate bulk precipitation could be occurring for FFA molecules in solution and that PVP-VA was an effective precipitation inhibitor for all three co-crystals studied in solution. 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