{"id":{"repo_id":"bradford","oai_identifier":"oai:bradscholars.brad.ac.uk:10454/14630"},"canonical_url":"https://search.dev.ndltd.org/etd/bradford/oai:bradscholars.brad.ac.uk:10454/14630","repository":{"repo_id":"bradford","name":"University of Bradford","base_url":"https://bradscholars.brad.ac.uk/oai/request"},"display":{"title":"The Formation of Pharmaceutical Co-crystals by Spray Drying. An Investigation into the Chemical and Physical Factors Affecting the Production of Pharmaceutical Co-crystals by Fast Evaporation and Spray Drying","abstract":"Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.","abstract_html":"Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.","abstract_has_math":false,"creators":["Mehta, Bhanvi"],"institution":"University of Bradford","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Paradkar, Anant R","Grimsey, Ian M."],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-24T01:15:46Z","subjects":["Spray drying","Rotavap","Co-crystal","Solubility","Caffeine","Carbamazepine","Theophylline"],"languages":["en"],"rights":["\"Creative
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The University of Bradford theses are licenced under a Creative Commons Licence."],"dc:subject":["Spray drying","Rotavap","Co-crystal","Solubility","Caffeine","Carbamazepine","Theophylline"],"dc:title":["The Formation of Pharmaceutical Co-crystals by Spray Drying. An Investigation into the Chemical and Physical Factors Affecting the Production of Pharmaceutical Co-crystals by Fast Evaporation and Spray Drying"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-24T01:15:46Z"}