The study of steroid distribution in emulsions by the spin probe method
DOI:
https://doi.org/10.24959/cphj.17.1430Keywords:
steroid, spin probe, EPR spectrum, solvent, emulsion, distribution, isotropic constant, time of rotational diffusion correlationAbstract
The solubility of the active substance, which determines its dispersed state in a dosage form, is a significant pharmaceutical factor for providing the required functional characteristics of a medicinal product, its effectiveness, safety and, if necessary, bioavailability.
Aim. To study the behavior of spin probes based on steroids in some solvents, micelles of nonionic surfactants, as well as emulsions both of type 1 and type 2 with a different composition of excipients in order to predict bioavailability, efficacy and safety of medicinal products with steroids.
Materials and methods. The studies were carried out by the spin probe method. Two spin probes based on steroids with different localization of the nitroxide radical in their molecules were used.
Results. The disperse state and localization of steroid molecules in some solvents, surfactant micelles and emulsions both of type 1 and type 2 were identified using the shape of EPR spectra, the isotropic constant values and the rotational correlation time of two different spin probes. It has been found out that the spin probes based on steroids with different hydrophilic-lipophilic properties are distributed differently in the dispersion medium and in the dispersed phase of emulsions. The emulsion type, the chemical nature, the composition and polarity of the dispersion medium and the dispersed phase also cause differences in distribution of steroids in emulsions.
Conclusions. Different localization and disperse state of steroids in vehicles can affect the effectiveness of their pharmacological action, bioavailability in different routes of administration and the safety of drugs. In the pharmaceutical development of drugs it is necessary to study the solubility of steroids, their distribution between the dispersed phase and the dispersion medium of emulsions, the disperse state in the vehicles, as well as to carry out biopharmaceutical and/or pharmacological screening studies in order to select the optimal composition of the medicinal product.
References
Liapunov, M., Bezugla, O., Pidpruzhnykov Yu. et al. (2016). ST–N MOZU 42–3.0:2011. Likarski zasoby. Farmatsevtychna rozrobka
(ICH Q8). Kyiv, MOZ Ukrainy, MORION, 1, 39–74.
Liapunov, N. A., Bezuglaia, E. P., Stolper, Yu. M. et al. (2011). Farmatsevticheskaia razrabotka lekarstvennykh preparatov.
Glava 9. Kharkov: NTMT, 3, 1419–1512.
Likhtenshtein, G. I. (1974). Metod spinovykh zondov v molekuliarnoi biologii. Moscow: Nauka, 256.
Kuznetcov A. N. (1976). Metod spinovogo zonda (Osnovy i primenenie). Moscow: Nauka, 210.
Bobko, A. A., Kirilyuk, I. A., Gritsan, N. P., Polovyanenko, D. N., Grigor’ev, I. A., Khramtsov, V. V., Bagryanskaya, E. G. (2010).
EPR and Quantum Chemical Studies of the pH–sensitive Imidazoline and Imidazolidine Nitroxides with Bulky Substituents.
Applied Magnetic Resonance, 39 (4), 437–451. doi: 10.1007/s00723–010–0179–z
Misharin, A. Y., Stulov, S. V., Tkachev, Y. V., Timofeev, V. P. (2011). Spin Labeled [17(20)E]–pregna–5,17(20)–dien–21–oilamides.
Synthesis, Structure, and Possible Applications. 6th SPIN Conference. Marseille, Poster/Oral № XX.
Rowe, R. C., Sheskey, P. J., Owen, S. C. (2006). Pharmaceutical Excipients. Pharmaceutical Press, London.
European Pharmacopoeia. 9th Edition. (2016). European Directorate for the Quality of Medicines (EDQM). Council of Europe,
Strasbourg Cedex, France, 4016.
Krasnoporova, A. P., Yukhno, G. D., Liapunova A. N. et al. (2011). Visnyk Kharkivskoho natsionalnoho universytetu, 20 (43),
–155.
Barel, A. O., Paye, M., Maibach, H. I., Dekker, M. (2001). Handbook of Cosmetic Science and Technology. New York–Basel, 903.
Kovalenko, V. N. (2016). Kompendium 2016 – lekarstvennye preparaty. Kiev: MORION, 2416.
Rusanov, A. I. (1992). Mitcelloobrazovanie v rastvorakh poverhnostno–aktivnykh veshchestv. Sankt– Peterburg: Khimiia, 280.
Liapunov, N. A., Ivanov, L. V., Sergienko, N. G. et al. (1985). Farmatciia, 5, 25–29.
Bashura, G. S., Liapunov, N. A., Dilbarkhanov, R. D. et al. (1977). Gidrofilno–lipofilnyi balans (GLB) i metody ego opredeleniia.
Izv. AN KazSSR. Ser. biolog., 5, 74–80.
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