Abstract
Knowledge of the solid state is of great importance in the development of a new active pharmaceutical ingredient, since the solid form often dictates the properties and performance of the drug. In the present study, solid state characteristics of the sodium salt of the candidate cholesterol reducing compound eritadenine, 2(R), 3(R))-dihydroxy-4-(9-adenyl)-butanoic acid, were investigated. The compound was crystallized by slow cooling from water and various aqueous ethanol solutions, at different temperatures. Further, the compound solution was subjected to lyophilization and to high vacuum drying. The resulting solids were screened for polymorphism by micro Raman spectroscopy (λex = 830 nm) and the crystallinity was investigated by X-ray powder diffraction. Further, thermal analysis was applied to study possible occurrence of solvates or hydrates. Solids obtained from slow cooling showed crystallinity, whereas rapid cooling gave rise to more amorphous solids. Analysis of difference spectra of the Raman data for solids obtained from slow cooling of solution revealed subtle differences in the structures between crystals derived from pure water and crystals derived from aqueous ethanol solutions. Finally, from the thermal analysis it was deduced that crystals obtained from pure water were stoichiometrically dihydrates whereas crystals obtained from aqueous ethanol solutions were 2.5 hydrates; this formation of different hydrates were supported by the Raman difference analysis.
Highlights
Cardiovascular disease is one of the most serious health concerns in Western society and hypercholesterolemia is a well established risk factor for the development of such disease
The solubility of sodium eritadenate was comparatively high in pure water and virtually insoluble in absolute ethanol (Figure 2); the highest ethanol concentration used for crystallization in this study was 50% (v/v)
Sodium eritadenate was crystallized from water and aqueous ethanol solutions, by controlled cooling, and subjected to rapid cooling from water solutions
Summary
Cardiovascular disease is one of the most serious health concerns in Western society and hypercholesterolemia is a well established risk factor for the development of such disease. Various statins, some of which were originally isolated from fungi such as Aspergillus terreus [1], are frequently used. Another hypocholesterolemic compound of fungal origin is D-eritadenine, 2(R), 3(R)-dihydroxy-4-(9-adenyl)-butanoic acid (Figure 1), found in the shiitake mushroom, Lentinus edodes[2,3]. The shiitake mushroom has been shown to lower the blood cholesterol in both animals and humans[4,5,6], and the cholesterol reducing mechanism of eritadenine has been investigated in several studies on rats [2,3,7,8,9,10]. In search for new cholesterol re- ducing drugs, eritadenine might have a potential as an AJAC
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