Abstract
In the present study, we report on the thermal properties of a series of benzodiazepines. The heat of fusion varied between approximately 25 and 40 kJ mol−1, except for oxazepam and lorazepam where dimerization in the solid state increased the heat of fusion to 78.54(±0.37) and 77.03 (±0.84)kJ mol−1, respectively. Heating alprazolam at a low rate (0.5 K min−1) showed that polymorphs I and II are an enantiotropic pair with a solid-solid transition at 481.4 K It was shown that all benzodiazepines could be transformed to the glassy state by cooling fused samples, irrespective of the cooling rate. The size of the relaxation endotherm accompanying the glass transition increased by heating the glassy drugs at a higher rate through Tg or by cooling the fused samples at a slower rate. The time dependence of the glass to liquid transition can be described to a good approximation as a first order transformation. The Gordon-Taylor equation was used to predict Tg of a binary mixture of temazepam, diazepam or prazepam with polyHEMA. It was shown that the predictability was acceptable as long as the drug concentration was below 10%w/w; at higher concentration, specific drug-polymer interactions causing changes in free volume of the system could not be ignored.
Similar content being viewed by others
References
W. L. Chiou and S. Riegelman, J. Pharm. Sci., 60 (1971) 1281.
J. L. Ford, Pharm. Acta Helv., 61 (1986) 69.
M. Yoshioka, B. C. Hancock and G. Zografi, J. Pharm. Sci., 83 (1994) 1700.
M. Yoshioka, B. C. Hancock and G. Zografi, J. Pharm. Sci., 84 (1995) 983.
M. Otsuka and N. Kaneniwa, Chem. Pharm. Bull., 36 (1988) 4026.
Y. Roos and M. Karel, J. Food. Sci., 56 (1991) 38.
M. J. Richardson, In V. B. F. Mathot (ed.), Calorimetry and thermal analysis of polymers, Hanser publishers, New York 1994, pp. 169.
B. C. Hancock and G. Zografi, J. Pharm. Sci., 86 (1997) 1.
N. Laihanen and J. Yliruusi, STP Pharma Sci., 6 (1996) 264.
R. J. Behme, D. Brooke, R. F. Farney and T. T. Kensler, J. Pharm. Sci., 74 (1985) 1041.
G. A. Neville, H. D. Beckstead and H. F. Shurvell, Vibr. Spectr., 1 (1991) 287.
G. A. Neville, H. D. Beckstead and H. F. Shurvell, Can. J. Appl. Spectr., 37 (1992) 18.
E. Fukuoka, M. Mikita and S. Yamamura, Chem. Pharm. Bull., 34 (1986) 4314.
A. T. Serajudin, M. Rosoff and D. Mufson, J. Pharm. Pharmacol., 38 (1986) 219.
M. P. Summers. J. Pharm. Sci., 67 (1978) 1606.
C. A. Angell, Science 267 (1995) 1924.
B. C. Hancock, S. L. Shamblin and G. Zografi, Pharm. Res., 12 (1995) 799.
J. M. Barton, Polymer, 10 (1969) 151.
H. A. Schneider, Polymer, 30 (1989) 771.
J. L. Ford, Drug Dev. Ind. Pharm., 13 (1987) 1741.
R. J. Timko and N. G. Lordi, J. Pharm, Sci., 68 (1979) 601.
S. K. Dordunoo, J. L. Ford and M. H. Rubinstein, J. Pharm. Pharmacol., 49 (1997) 390.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Van den Mooter, G., Van den Brande, J., Augustijns, P. et al. Glass Forming Properties of Benzodiazepines and Co-evaporate Systems with Poly(hydroxyethyl Methacrylate). Journal of Thermal Analysis and Calorimetry 57, 493–507 (1999). https://doi.org/10.1023/A:1010172125782
Issue Date:
DOI: https://doi.org/10.1023/A:1010172125782