{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:53:25Z","timestamp":1789826005008,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The solubility and phase behavior of APIs are crucial for the development of medicines and ensuring their stability. However, conventional experimental approaches often do not allow for the precise determination of phase transitions and solubility limits, especially for poorly soluble compounds. Purpose: The aim of this study was to demonstrate the possibility of using the laser microinterferometry method, traditionally used to define the phase equilibria of polymer systems, to determine the thermodynamic solubility of the APIs. Methods: Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25\u2013130 \u00b0C. Dissolution kinetics was estimated at 25 \u00b0C. Hansen solubility parameter calculations were also performed for comparison. Results: Darunavir is practically insoluble in olive and vaseline oils. In water and glycerol, an amorphous equilibrium with an upper critical solution temperature was observed, and phase diagrams were constructed for the first time. In alcohols, glycols, and ethoxylated polyethylene glycol ether obtained from castor oil, darunavir showed high solubility, accompanied by the formation of crystalline solvates. Kinetic evaluation showed that the dissolution rate of darunavir in methanol is four times faster than in ethanol and thirty times faster than in isopropanol. Comparison of the obtained data with previously published and calculated values of solubility parameters demonstrates a good correlation. Conclusions: Laser microinterferometry has been demonstrated as a potential tool for determining the thermodynamic solubility of APIs. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070875","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T06:01:33Z","timestamp":1751522493000},"page":"875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Laser Microinterferometry for API Solubility and Phase Equilibria: Darunavir as a Case Example"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-1630","authenticated-orcid":false,"given":"Veronika","family":"Makarova","sequence":"first","affiliation":[{"name":"A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky pr. 29, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-9615","authenticated-orcid":false,"given":"Mark","family":"Mandrik","sequence":"additional","affiliation":[{"name":"A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky pr. 29, 119991 Moscow, Russia"},{"name":"Department of Pharmaceutical Technology, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of Health of the Russian Federation, 8-2 Trubetskaya str., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-7906","authenticated-orcid":false,"given":"Sergey","family":"Antonov","sequence":"additional","affiliation":[{"name":"A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky pr. 29, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ddtec.2018.06.001","article-title":"Brief overview of solubility methods: Recent trends in equilibrium solubility measurement and predictive models","volume":"27","year":"2018","journal-title":"Drug Discov. Today Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/1520-6017(200104)90:4<521::AID-JPS1009>3.0.CO;2-B","article-title":"Comparison of chromatographic and spectroscopic methods used to rank compounds for aqueous solubility","volume":"90","author":"Pan","year":"2001","journal-title":"J. Pharm. 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