Influence of compression on water sorption, glass transition, and enthalpy relaxation behavior of freeze-dried amorphous sugar matrices

• Published in: International journal of pharmaceutics Vol. 408; no. 1-2; pp. 76 - 83
• Main Authors: Imamura, Koreyoshi, Kagotani, Ryo, Nomura, Mayo, Tanaka, Kazuhiro, Kinugawa, Kohshi, Nakanishi, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.04.2011; Elsevier
• Subjects: Adsorption; Amorphous sugar; Biological and medical sciences; Carbohydrates - chemistry; Compression; diffusivity; Drug Stability; enthalpy; Excipients - chemistry; Freeze Drying; General pharmacology; glass transition; Glass transition temperature; Medical sciences; pharmaceutical industry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Porosity; sorption; Structural relaxation; sugars; Technology, Pharmaceutical - methods; Thermodynamics; Water - chemistry; water content; Water sorption; water vapor; Amorphous sugar; Compression; Water sorption; Structural relaxation; Glass transition temperature; Freeze-drying; Freeze dried product; Freeze drying; Pharmaceutical technology; Structure relaxation; Glass transition; Behavior; Sugar
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.01.052

An amorphous matrix comprised of sugar molecules are frequently used in the pharmaceutical industry. The compression of the amorphous sugar matrix improves the handling. Herein, the influence of compression on the water sorption of an amorphous sugar matrix was investigated. Amorphous sugar samples were prepared by freeze-drying, using several types of sugars, and compressed at 0–443MPa. The compressed amorphous sugar samples as well as uncompressed samples were rehumidified at given RHs, and the equilibrium water content and glass transition temperature (Tg) were then measured. Compression resulted in a decrease in the equilibrium water content of the matrix, the magnitude of which was more significant for smaller sized sugars. Diffusivity of water vapor in the sample was also decreased to one-hundredth by the compression. The Tg value for a given RH remained unchanged, irrespective of the compression. Accordingly, the decrease in Tg with increasing water content increased as the result of compression. The structural relaxation of the amorphous sugar matrices were also examined and found to be accelerated to the level of a non-porous amorphous sugar matrix as the result of the compression. The findings indicate that pores contained in freeze-dried sugar samples interfere with the propagation of structural relaxation.