{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:49Z","timestamp":1760060269399,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002597","name":"Kyung Hee University","doi-asserted-by":"publisher","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}],"id":[{"id":"10.13039\/501100002597","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Basic Science Institute","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}]},{"name":"Korea Basic Science Institute","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}]},{"name":"Korea Institute for Advancement of Technology","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}]},{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"],"award-info":[{"award-number":["KHU-20230884","2021R1C1C2006535","RS-2023-00257666","RS-2024-00403164","2019R1A6C1010052","P0017363","RS-2025-02263424"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: Transforming poorly soluble crystalline drugs into their amorphous form is a well-established strategy in pharmaceutical science to enhance their solubility and improve their clinical efficacy. However, developing amorphous forms of organic drugs for pharmaceutical applications presents significant technical hurdles due to the lack of suitable analytical tools for the amorphization process. Carbamazepine is a crystalline BCS class II drug commonly used for epilepsy and trigeminal neuralgia, whose clinical efficacy is compromised by its low solubility and slow dissolution. Therefore, this study focuses on investigating the amorphization of carbamazepine to enhance its solubility by using a micro-droplet precipitation system. Methods: These micro-droplets serve as individual reactors, enabling homogeneous nucleation for precipitation of carbamazepine. During crystallization, carbamazepine undergoes an intermediate liquid\u2013liquid phase transition characteristic of two-step nucleation. By varying the solvent\u2019s composition (methanol\/water), we characterized the kinetics and stability of the intermediate liquid phase under various conditions. Results: Our results indicate that carbamazepine can undergo either a one-step liquid-to-amorphous-solid phase transition or a two-step liquid-to-crystalline-solid phase transition. Notably, both transitions pass through a liquid-to-dense-liquid phase separation process starting from the supersaturated solution, where the generated intermediate phases exhibit different sizes and numbers that are influenced by the solvent and its concentration. Conclusions: Our findings not only elucidate the mechanism underlying the carbamazepine phase transition but also propose a novel method for studying the amorphous process, which could be broadly applicable to other poorly soluble pharmaceutical compounds and may be helpful to amorphous formulations production, potentially offering significant improvements in drug efficacy and patient compliance.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081035","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T08:10:32Z","timestamp":1754899832000},"page":"1035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two-Step Nucleation and Amorphization of Carbamazepine Using a Micro-Droplet Precipitation System"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaoling","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering (Integrated Engineering Program), College of Engineering, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheongcheon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Materials Science, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Electrode Development Team, Samsung SDI Co., Ltd. R&D Center, 130 Samsung-ro, Yeongtong-gu, Suwon 16678, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Min","family":"Go","sequence":"additional","affiliation":[{"name":"Corning Technology Center Korea, Corning Precision Materials Co., Ltd., 212 Tangjeong-ro, Asan 31454, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suha","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering (Integrated Engineering Program), College of Engineering, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonghwi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Materials Science, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Kyu","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-4310","authenticated-orcid":false,"given":"Jaehyeong","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering (Integrated Engineering Program), College of Engineering, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Seok","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering (Integrated Engineering Program), College of Engineering, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1002\/jps.21650","article-title":"Supersaturating Drug Delivery Systems: The Answer to Solubility-Limited Oral Bioavailability","volume":"98","author":"Brouwers","year":"2009","journal-title":"J. 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