Effect of Preparation Method on Physical Properties of Amorphous Trehalose Article DOI:
Cite this article as: Surana, R., Pyne, A. & Suryanarayanan, R. Pharm Res (2004) 21: 1167. doi:10.1023/B:PHAM.0000033003.17251.c3 Abstract . To determine the effect of preparation method on the physical properties of amorphous trehalose. Purpose . Amorphous anhydrous trehalose was prepared by four different methods, viz., freeze-drying, spray-drying, dehydration, and melt quenching. The glass transition temperature (T Methods g), enthalpic relaxation behavior, and crystallization were studied by differential scanning calorimetry, whereas X-ray diffractometry was used for phase identification. The rate and extent of water uptake at different relative humidity values were also obtained. . Though the enthalpic relaxation and crystallization behaviors were influenced by the method of preparation of amorphous trehalose, the T Results g and fragility were not. The phase prepared by dehydration showed the highest enthalpic recovery at T g, indicating that aging may have occurred during preparation. Among the four methods used, trehalose prepared by dehydration had the highest tendency to crystallize, whereas there was no crystallization in melt-quenched amorphous trehalose. The method of preparation influenced not only the rate and extent of water sorption but also the phase crystallized. Water vapor sorption removed the effects of structural history in the amorphous phase formed by dehydration. . The method of preparation strongly influenced the pharmaceutically relevant properties of amorphous trehalose. The resistance to crystallization can be rank ordered as trehalose prepared by dehydration < freeze-dried mF spray-dried < melt-quenched. The rate of water sorption can be rank ordered as trehalose prepared by dehydration < freeze-dried < spray-dried. Conclusions amorphous dehydration differential scanning calorimetry (DSC) freeze-drying glass transition temperature (T g) method of preparation spray-drying thermal history trehalose dihydrate References
C. A. Angell. Formation of glasses from liquids and biopolymers.
C. A. Angell. Relaxation in liquids, polymers and plastic crystals-Strong/fragile patterns and problems.
J. Non-Cryst. Solids
Relaxation in Viscous Liquids and Glasses
, The American Ceramic Society, Columbus, OH, 1985.
M. J. Pikal, A. L. Lukes, J. E. Lang, and K. Gaines. Quantitative crystallinity determination for β-lactam antibiotics by solution calorimetry: Correlations with stability.
J. Pharm. Sci.
B. C. Hancock, E. Y. Shalaev, and S. L. Shamblin. Polyamorphism: A pharmaceutical science perspective.
J. Pharm. Pharmacol.
E. Yonemochi, Y. Ueno, G. Buckton, A. Moffat, T. Oguchi, and K. Yamamoto. Differences in crystallization behavior between quenched and ground amorphous ursodeoxycholic acid.
V. Andronis and G. Zografi. Crystal nucleation and growth of indomethacin polymorphs from the amorphous state.
J. Non-Cryst. Solids
Y. Li, J. Han, G. G. Z. Zhang, D. J. W. Grant, and R. Suryanarayanan.
dehydration of carbamazepine dihydrate: A novel technique to prepare amorphous anhydrous carbamazepine.
Pharm. Dev. Technol.
B. C. Hancock and G. Zografi. Characteristics and significance of the amorphous state in pharmaceutical systems.
J. Pharm. Sci.
K. Suzuki and A. C. Wright. Structure of non-crystalline materials.
J. Non-Cryst Solids
E. Y. Shalaev and G. Zografi. The concept of “structure” in amorphous solids from the perspective of the pharmaceutical sciences. In H. Levine (ed.),
Progress in Amorphous Food and Pharmaceutical Systems
, Royal Society of Chemistry, Cambridge, UK, 2002 pp. 11-30.
I. Tsukushi, O. Yamamuro, and H. Suga. Heat capacities and glass transitions of ground amorphous solid and liquid-quenched glass of tri-O-methyl-β-cyclodextrin.
J. Non Cryst. Solids
E. F. Riebling. Relations between phase diagrams and the structure of glass-forming oxide melts.
J. J. Seyer, P. E. Luner, and M. S. Kemper. Application of diffuse reflectance near-infrared spectroscopy for determination of crystallinity.
J. Pharm. Sci.
J. F. Willart, A. De Gusseme, S. Hemon, G. Odou, F. Danede, and M. Descamps. Direct crystal to glass transformation of trehalose induced by ball milling.
Solid State Commun.
S. P. Ding, J. Fan, J. L. Green, Q. Lu, E. Sanchez, and C. A. Angell. Vitrification of trehalose by water loss from its crystalline dihydrate.
J. Therm. Anal.
R. Suryanarayanan. Determination of the relative amounts of α-carbamazepine and β-carbamazepine in a mixture by powder x-ray diffractometry.
J. Han and R. Suryanarayanan. A method for the rapid evaluation of the physical stability of pharmaceutical hydrates.
L. S. Taylor and P. York. Characterization of the phase transitions of trehalose dihydrate on heating and subsequent dehydration.
J. Pharm. Sci.
L. S. Taylor, A. C. Williams, and P. York. Particle size dependent molecular rearrangements during the dehydration of trehalose dihydrate.
F. Shafizadeh and R. A. Susott. Crystalline transitions of carbohydrates.
J. Org. Chem.
L. S. Taylor.
Carbohydrates as Protein Stabilizing Agents, Ph.D. thesis, University of Bradford, 1996.
H. Levine and L. Slade. Water as a plasticizer: Physico-chemical aspects of low-moisture polymeric systems. In F. Franks (ed.),
Water Science Review
, Cambridge University Press, Cambridge, 1988 pp. 79-185.
R. Surana, A. Pyne, and R. Suryanarayanan. Effect of aging on the physical properties of amorphous trehalose.
Pharm. Res. (2004).
A. Pyne, R. Surana, and R. Suryanarayanan. Enthalpic relaxation in frozen aqueous trehalose solutions.
C. T. Moynihan, A. J. Easteal, J. Wilder, and J. Tucker. Dependence of the glass transition temperature on heating and cooling rate.
J. Phys. Chem.
C. T. Moynihan, S. K. Lee, M. Tatsumisago, and T. Minami. Estimation of activation energies for structural relaxation and viscous flow from DTA and DSC experiments.
J. D. Hancock and J. H. Sharp. Method of comparing solid-state kinetic data and its application to the decomposition of kaolinite, brucite, and barium carbonate.
J. Am. Ceram. Soc.
H. A. Iglesias, J. Chirife, and M. P. Buera. Adsorption isotherm of amorphous trehalose.
J. Sci. Food Agr.
M. Rani, R. Govindarajan, R. Surana, and R. Suryanarayanan. Preparation, characterization and physical stability evaluation of the α-polymorph of anhydrous trehalose.
AAPS PharmSci, 2003; 5(S4). Abstract M1295. Available at: http://www.aapspharmsci.org/.
A. Saleki-Gerhardt, C. Ahlneck, and G. Zografi. Assessment of disorder in crystalline solids.
Int. J. Pharm.
Google Scholar Copyright information
© Plenum Publishing Corporation 2004