Abstract
Purpose.
To determine if hydration of long- and medium-chain triglyceride oils (long = soybean and olive, medium = Miglyol 812) has a significant effect on the ability to solubize the model hydrophobic compounds progesterone, estradiol, and testosterone.
Methods.
Soybean, olive, and Miglyol 812 oils were treated in one of two ways: hydrated or desiccated (hydrated, then dried). Solubility of 3H-labeled progesterone, estradiol, and testosterone in the triglycerides was measured by liquid scintillation counting.
Results.
Both hydration state and chain length of the triglycerides were shown to have a significant influence on the solubility of steroids. Solubility of estradiol hemihydrate and testosterone monohydrate in hydrated triglycerides is decreased by about 30%–40% compared with desiccated oils. The solubility of anhydrous testosterone was decreased by hydration of the oils due to conversion to the monohydrate crystalline form. In contrast, the solubility of progesterone was insensitive to the state of hydration of all oils.
Conclusions.
Hydration of triglyceride oils caused a significant decrease in the solubility of steroids, which may form hydrates or hemihydrates. Results suggest the need for knowledge of the hydration state of triglyceride oils to be used as pharmaceutical excipients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
1. J. R. Robinson. Introduction: semi-solid formulations for oral drug delivery. Bulletin Technique Gattefosse 89:11–13 (1996).
2. A. J. Humberstone and W. N. Charman. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv. Drug Del. Rev 25:103–128 (1997).
3. B. J. Aungst. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J. Pharm. Sci. 82:979–987 (1993).
4. A. T. Serajuddin, P. C. Sheen, D. Mufson, D. F. Berstein, and M. A. Augustine. Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersion. J. Pharm. Sci. 77:414–417 (1988).
5. N. H. Shah, M. T. Carvajal, C. I. Patel, M. H. Infeld, and A. W. Malick. Self-emulsifying drug delivery systems (SEDDS) with polyglycolysed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int. J. Pharm. 106:15–23 (1994).
6. R. A. Myers and V. Stella. Systemic bioavailability of penclomidine (NSC-338720) from oil-in-water emulsions administered intraduodenally to rats. Int. J. Pharm. 78:217–226 (1992).
7. R. A. Schwendener and H. Schott. Lipophilic1-beta-D-arabinofuranosyl cytosine derivatives in liposomal formulations for oral and parenteral antileukemic therapy in the murine L1210 leukemia model. J. Cancer Res. Clin. Oncol.w 122:723–726 (1996).
8. Y. Cao, M. Marra, and B. Anderson. Predictive relationships for the effects of triglyceride ester concentration and water uptake on solubility and partitioning of small molecules into lipid vehicles. J. Pharm. Sci. 93:2768–2779 (2004).
9. U. Jain, W. Higuchi, C. Liu, P. Lee, and N. Mazer. Cholesterol thermodynamic activity determinations in bile salt-lecithin-cholesterol systems and cholesterol-rich liquid crystalline mesophase formation. Pharm. Res. 9:792–799 (1992).
10. E. Shefter and T. Higuchi. Dissolution behavior of crystalline solvated and nonsolvated forms of some pharmaceuticals. J. Pharm. Sci. 52:781–791 (1963).
11. A. Thakkar and N. Hall. Micellar solubilization of testosterone III: dissolution behavior of testosterone in aqueous solutions of selected surfactants. J. Pharm. Sci. 58:68–71 (1969).
12. B. Haner and D. Norton. Crystal data. I. For some pregnenes and pregnadienes. Acta Crystallogr. 17:1610 (1964).
13. B. Jerslev, S. Frokjaer, and P. Thorbek. Organic solid phase analysis II. Two unexpected cases of pseudopolymorphism. Arch. Pharm. Chemi. Sci. Ed 9:123–130 (1981).
14. H. Fung and T. Higuchi. Molecular interactions and solubility of polar nonelectrolytes in nonpolar solvents. J. Pharm. Sci. 60:1782–1788 (1971).
15. Y. Yamaoka, R. Roberts, and V. Stella. Low-melting phenytoin prodrugs as alternative oral delivery methods for phenytoin: a model for other high-melting sparingly water-soluble drugs. J. Pharm. Sci. 72:400–405 (1983).
16. B. K. Kang, J. S. Lee, S. K. Chon, S. Y. Jeong, S. H. Yuk, G. Khang, H. B. Lee, and S. H. Cho. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int. J. Pharm. 274:65–73 (2004).
17. C. Malcolmson, C. Satra, S. Kantaria, A. Sidhu, and M. J. Lawrence. Effect of oil on the level of solubilization of testosterone propionate into nonionic oil-in-water microemulsions. J. Pharm. Sci. 87:109–116 (1998).
18. T. R. Kommuru, B. Gurley, M. A. Khan, and I. K. Reddy. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int. J. Pharm. 212:233–246 (2001).
19. E. Lamcharfi, G. Kunesch, C. Meyer, and B. Robert. Investigation of cyclodextrin inclusion compounds using FT-IR and Raman spectroscopy. Spectrochimica Acta Part A 51:1861–1870 (1995).
20. F. Parker and K. Bhaskar. Self-association of cholesterol and its interaction with triglycerides. An IR study. Biochemistry 7:1286–1290 (1968).
21. H. Zhu and D. Grant. Influence of water activity in organic solvent + water mixtures on the nature of the crystallizing drug phase. 2. Ampicillin. Int. J. Pharm. 139:33–43 (1996).
22. J. De Smidt, J. Fokkens, H. Grijseels, and D. Crommelin. Dissolution of theophylline monohydrate and anhydrous theophylline in buffer solutions. J. Pharm. Sci. 75:497–501 (1986).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Land, L., Li, P. & Bummer, P. The Influence of Water Content of Triglyceride Oils on the Solubility of Steroids. Pharm Res 22, 784–788 (2005). https://doi.org/10.1007/s11095-005-2595-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-005-2595-6