{"id":{"repo_id":"bradford","oai_identifier":"oai:bradscholars.brad.ac.uk:10454/19698"},"canonical_url":"https://search.dev.ndltd.org/etd/bradford/oai:bradscholars.brad.ac.uk:10454/19698","repository":{"repo_id":"bradford","name":"University of Bradford","base_url":"https://bradscholars.brad.ac.uk/oai/request"},"display":{"title":"Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of Cocrystals","abstract":"Pharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals.","abstract_html":"Pharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals.","abstract_has_math":false,"creators":["Jhariya, Aditya N."],"institution":"University of Bradford","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Vangala, Venu R.","Paradkar, Anant R"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021","date_published":"2021","updated_at":"2026-07-24T01:15:46Z","subjects":["Co-crystallisation","Crystal engineering","Mechanical properties","Tabletability","Solubility","Physicochemical stability","Z prime","Antimicrobial activity","X-ray crystallography","High-Performance Liquid Chromatography (HPLC)"],"languages":["en"],"rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10454/19698","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Vangala, Venu R.","Paradkar, Anant R"]},{"key":"dc:creator","label":"Author","values":["Jhariya, Aditya N."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-11-22T15:37:18Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-11-22T15:37:18Z"]},{"key":"dc:date.issued","label":"Date","values":["2021"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Faculty of Life Sciences"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Bradford"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Co-crystallisation","Crystal engineering","Mechanical properties","Tabletability","Solubility","Physicochemical stability","Z prime","Antimicrobial activity","X-ray crystallography","High-Performance Liquid Chromatography (HPLC)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10454/19698"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Pharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals."]},{"key":"dc:title","label":"Title","values":["Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of Cocrystals"]}]}],"canonical_facts":{"dc:contributor.advisor":["Vangala, Venu R.","Paradkar, Anant R"],"dc:creator":["Jhariya, Aditya N."],"dc:date.accessioned":["2023-11-22T15:37:18Z"],"dc:date.available":["2023-11-22T15:37:18Z"],"dc:date.issued":["2021"],"dc:description.abstract":["Pharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals."],"dc:identifier.uri":["http://hdl.handle.net/10454/19698"],"dc:language.iso":["en"],"dc:publisher.department":["Faculty of Life Sciences"],"dc:publisher.institution":["University of Bradford"],"dc:rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"dc:subject":["Co-crystallisation","Crystal engineering","Mechanical properties","Tabletability","Solubility","Physicochemical stability","Z prime","Antimicrobial activity","X-ray crystallography","High-Performance Liquid Chromatography (HPLC)"],"dc:title":["Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of Cocrystals"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-24T01:15:46Z"}