Quantitative correlation between initial dissolution rate and heat of solution of drug.
OBJECTIVE
The aim of this study is to estimate the initial dissolution rate of drug substances by isothermal microcalorimetry. A theory was presented on the basis of Gibbs free energy and the Noyes-Whitney equation.


METHODS
Polymorphic forms and quenched glass of indomethacin, and some different crystallinity samples of terfenadine were used. The heats of solution of samples were measured by isothermal microcalorimetry. The initial dissolution rates of samples were measured by rotating disk method at 25 degrees C.


RESULTS
Each drug showed a linear correlation between the heats of solution and the logarithms of initial dissolution rate, irrespective of their different crystal structure, such as polymorphic forms and crystallinity. The logarithms of initial dissolution rates were well correlated with the degree of crystallinity obtained by the isothermal microcalorimetry.


CONCLUSIONS
The initial dissolution rates of drug substances could be estimated quantitatively from the heats of solution as estimated from the present theory. Isothermal microcalorimetry was extremely useful for the estimation of the initial dissolution rates of polymorphs and of partially crystalline samples.
Terada
K
K
Department of Pharmaceutics, School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan. terada@phar.toho-u.ac.jp
Kitano
H
H
Yoshihashi
Y
Y
Yonemochi
E
E
D006634:Histamine H1 Antagonists / Q000737:chemistry; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D016593:Terfenadine / Q000737:chemistry; D014961:X-Ray Diffraction
D006634:Histamine H1 Antagonists; D019999:Pharmaceutical Solutions; D016593:Terfenadine