The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides

• Published in: Pharmaceutical research Vol. 29; no. 10; pp. 2684 - 2697
• Main Authors: Heljo, Ville Petteri, Nordberg, Antti, Tenho, Mikko, Virtanen, Tommi, Jouppila, Kirsi, Salonen, Jarno, Maunu, Sirkka Liisa, Juppo, Anne Mari
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2012; Springer Nature B.V
• Subjects: Absorption; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Carbohydrates; Crystallization; Disaccharides - chemistry; Drug Storage; Freeze Drying - methods; Humidity; Medical Law; Molecular chemistry; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Plasticizers - chemistry; Research Paper; Transition Temperature; Water; Water - chemistry; crystallization; mobility; amorphous; disaccharide; water
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-011-0658-4

ABSTRACT Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T 1 H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, which may have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.