Abstract
Previously we have recrystallized estradiol with various organic solvents and investigated solvate molecules within estradiol crystals by using CP/MAS solid-state NMR. To investigate the effect of recrystallization solvents on the physicochemical properties of recrystallized estradiol, four different crystal habits of estradiol were recrystallized and their physicochemical properties were characterized by optical microscopy, solubility, and FT-IR measurements. Various crystal habits in size and shape were produced by the interaction between the estradiol and different solvents. Although the estradiol crystal habits prepared from ethanol and methanol had larger particle size, they were more soluble in PBS than those recrystallized from isopropanol and acetone. In spite of the low solubilities, the estradiols prepared from isopropanol and acetone were released in PBS and permeated through the hairless mouse skin similar to the others. Thus, although microscopic observation of recrystallized estradiols revealed that the estradiol had different crystal habits, the release and permeation properties of different estradiol crystals might be independent on the solvate molecules associated with the solvent used for recrystallization.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brind, J. L., Alani, E., Wheatley, V. R., and Orentreich, N. Analysis of Ear Sebum of the Syrian Hamster (Mesocrecetus Auratus) reveals pronounced sexual dimorphism. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 84B, 403–407 (1986).
Brittain, H. G., Polymorphism in Pharmaceutical Solids, vol. 95, Dekker, New York, pp. 1–21, 92–193, 350 (1999).
Byrn, S. R., Solid State Chemistry of Drugs, vol. 79. Academic Press, New York, pp. 17–18 (1982).
Byrn, S. R., Pfeiffer, R. R., Stephenson, G., Grant, D. J. W., and Gleason, W. B., Solid state pharmaceutical chemistry. Chem. Mater., 6, 1148–1158 (1994).
Epelbaum, B. M., Seitz, C., Magerl, A., Bickermann, M., and Winnacker, A., Natural growth habit of bulk AIN crystals. J. Cryst. Growth 265, 577–581 (2004).
Giron, D., Investigation of polymorphism and pseudopolymorphism in pharmaceuticals by combined thermo analytical techniques. J. Therm. Anal. Calorim., 64, 37–60 (2001).
Haleblian, J. K., Characterization of habits and crystalline modification of solids and their pharmaceutical application. J. Pharm. Sci., 64, 1269–1288 (1975).
Idezuki, Y., Watanabe, H., Hagiwara, M., Kanasugi, K., and Mori, Y., Mechanism of antithrombogenicity of a new heparinized hydrophilic polymer: chronic in vivo studies and clinical application. Trans. Am. Soc. Artif. Intern. Organs, 21, 436–449 (1975).
Iervolino, M., Cappello, B., Raghavan, S. L., and Hadgraft, J., Penetration enhancement of ibuprofen from supersaturation. Int. J. Pharm., 212, 131–141 (2001).
Kim, J. H. and Choi, H. K., Effect of additives on the crystallization and the permeation of ketoprofen from adhesive matrix. Int. J. Pharm., 236, 81–85 (2002).
Koizumi, A., Fujii, M., Kondoh, M., and Watanabe, Y., Effect of N-methyl-2-pyrrolidone on skin permeation of estradiol. Eur. J. Pharm. Biopharm., 57, 473–478 (2004).
Kotiyan, P. N. and Vavia, P. R., Eudragits: role as crystallization inhibitors in drug-in-adhesive transdermal systems of estradiol. Eur. J. Pharm. Biopharm., 52, 173–180 (2001).
Kraemer, G. R., Kraemer, R. R., Ogden, B. W., Kilpatrick, R. E., Gimpel, T. L., and Castracane, V. D., Variability of serum estrogens among postmenopausal women treated with the same transdermal estrogen therapy and the effect on androgens and sex hormone binding globulin. Fertil. Steril., 79, 534–542 (2003).
Latsch, S., Selzer, T., Fink, L., Horstmann, M., and Kreuter, J., Use of isothermal heat conduction microcalorimetry, X-ray diffraction, and optical microscopy for characterizarion of crystals grown in steroid combination-containing transdermal drug delivery systems, Eur. J. Pharm. Biopharm., 57, 397–410 (2004).
Lipp, R., Selection and use of crystallization inhibitors for matrix-type transdermal drug delivery systems containing sex steroids. J. Pharm. Pharmacol., 50, 1343–1349 (1998).
Lv, J., Qiu, L., and Qu, B., Controlled growth of three morphological structures of magnesium hydroxide nanoparticles by wet precipitation method. J. Cryst. Growth, 267, 676–684 (2004).
Maurin, M. B., Dittert, L. W., and Hussain, A. A., Mechanism of diffusion of monosubstituted benzoic acids through ethylenevinyl acetate copolymers. J. Pharm. Sci., 81, 79–84 (1992).
Park, J. S., Kang, H. W., Park, S. J., and Kim, C. K., Use of CP/MAS solid-state NMR for the characterization of solvate molecules within estradiol crystal forms. Eur. J. Pharm. Biopharm., 60, 407–412 (2005).
Precigoux, G., Marsau, P., Leroy, F., and Busetta, B., 17β-Hydroxymethyl-1,3,5(10)-estratrien-3-ol monohydrate. Acta Cryst. Sect B., 36, 749–751 (1980).
Raghavan, S. L., Trividic, A., Davis, A. F., and Hadgraft, J., Crystallization of hydrocortisone acetate:influence of polymers. Int. J. Pharm., 212, 213–221 (2001).
van Tonder, E. C., Maleka, T. S., Liebenberg, W., Song, M., Wurster, D. E., and de Villiers, M. M., Preparation and physicochemical properties of niclosamide anhydrate and two monohydrates. Int. J. Pharm., 269, 417–432 (2004).
Wadsten, T. and Lindberg, N. O., Polymorphism of estramustine I. J. Pharm. Sci., 78, 563–566 (1989).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, JS., Park, YJ., Kang, H.W. et al. Solvent effects on physicochemical behavior of estradiols recrystallized for transdermal delivery. Arch. Pharm. Res. 31, 111–116 (2008). https://doi.org/10.1007/s12272-008-1128-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-008-1128-3