Key Words:Crystallization ；Liquid–liquid phase separation ；Phase diagram ；Seeding ；Supersaturation control

Abstract:Liquid–liquidphaseseparation(LLPS)duringcrystallizationdevelopmentofpharmaceu-ticalsisbeingreportedincreasinglyinrecentyears.Itoftencausesqualityissuessuchasfailureofimpurityrejectandfragilemorphology.Inworstcases,crystallizationcan-notproceedatallafterLLPSoccurs.ManystudieshavebeenpublishedonLLPSduringcrystallizationandananalysisandsynthesisofthecurrentstate-of-artisneeded.Inthisreview,recentadvancesinLLPSresearchwillbesummarized,includingbrieftheoreticalinterpretationsofLLPS,characteristicsinphasediagramsandmeasurementmethodsforrepresentativemodelsystems,strategiestosuppressLLPS,crystallizationdevelopmentinthepresenceofLLPSandoptionswhendirectcrystallizationfailsduetoLLPS.ThisreviewaimstoprovideaframeworktodealwiththeoccurrenceofLLPSduringcrystallizationdevelopment

Volume:174

Issue:0

Translation or Not:no