{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yeh KL"],"funding":["Ministry of Science and Technology Taiwan"],"pagination":["1099"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9147162"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(5)"],"pubmed_abstract":["Form II paracetamol has captured the interest of researchers due to its improved compressibility. However, its low stability has made it difficult to be produced on a large scale with good reproducibility. In the present study, the selective polymorphic formation of paracetamol was carried out by cooling crystallization with four types of additives: adipic acid, fumaric acid, oxalic acid, and succinic acid. It was found that: (1) the more additives that were added, the higher the probability of forming Form II paracetamol; (2) Form II paracetamol could be induced by seeding the paracetamol aqueous solution with Form II paracetamol and fumaric acid crystals, and not the other three carboxylic acids; (3) a new solution complex of paracetamol-oxalic acid, evidenced by the solubility diagram, was responsible for the selective nucleation of Form II paracetamol in the oxalic acid aqueous solution; and (4) the range of the degree of supersaturation for nucleating Form II paracetamol was extended with the assistance of oxalic acid or fumaric acid. In large-scale crystallization, Form II paracetamol was produced by the continuous crystallization of 44 mg of paracetamol/mL in 50 wt% of fumaric acid aqueous solution with a flow rate of 150 mL/min."],"journal":["Pharmaceutics"],"pubmed_title":["Crystallization of Form II Paracetamol with the Assistance of Carboxylic Acids toward Batch and Continuous Processes."],"pmcid":["PMC9147162"],"funding_grant_id":["MOST 107-2221-E-008-037-MY3"],"pubmed_authors":["Lee HL","Yeh KL","Lee T"],"additional_accession":[]},"is_claimable":false,"name":"Crystallization of Form II Paracetamol with the Assistance of Carboxylic Acids toward Batch and Continuous Processes.","description":"Form II paracetamol has captured the interest of researchers due to its improved compressibility. However, its low stability has made it difficult to be produced on a large scale with good reproducibility. In the present study, the selective polymorphic formation of paracetamol was carried out by cooling crystallization with four types of additives: adipic acid, fumaric acid, oxalic acid, and succinic acid. It was found that: (1) the more additives that were added, the higher the probability of forming Form II paracetamol; (2) Form II paracetamol could be induced by seeding the paracetamol aqueous solution with Form II paracetamol and fumaric acid crystals, and not the other three carboxylic acids; (3) a new solution complex of paracetamol-oxalic acid, evidenced by the solubility diagram, was responsible for the selective nucleation of Form II paracetamol in the oxalic acid aqueous solution; and (4) the range of the degree of supersaturation for nucleating Form II paracetamol was extended with the assistance of oxalic acid or fumaric acid. In large-scale crystallization, Form II paracetamol was produced by the continuous crystallization of 44 mg of paracetamol/mL in 50 wt% of fumaric acid aqueous solution with a flow rate of 150 mL/min.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-06-01T12:38:48.885Z","creation":"2025-02-19T03:22:31.637Z"},"accession":"S-EPMC9147162","cross_references":{"pubmed":["35631685"],"doi":["10.3390/pharmaceutics14051099"]}}