Increasing Bioavailability of Very Poorly Water-Soluble Compounds. A Case Study of an Anti-Tumor Drug, Soloxolon Methyl | Sciact - CRIS-system of Boreskov Institute of Catalysis

Increasing Bioavailability of Very Poorly Water-Soluble Compounds. A Case Study of an Anti-Tumor Drug, Soloxolon Methyl Full article

Journal

Journal of Drug Delivery Science and Technology
ISSN: 1773-2247

Output data

Year: 2019, Volume: 49, Pages: 35-42 Pages count : 8 DOI: 10.1016/j.jddst.2018.10.025

Tags

Soloxolon methyl; Solid dispersions; Poorly water soluble drug; Freeze-drying

Authors

Ogienko A.G. ^1,2,3 , Markov A.V. ⁴ , Sen'kova A.V. ⁴ , Logashenko E.B. ⁴ , Salomatina O.V. ⁵ , Myz S.A. ^1,6 , Ogienko A.A. ^1,7 , Nefedov A.A. ^1,5 , Losev E.A. ^1,6 , Drebushchak T.N. ^1,6 , Salakhutdinov N.F. ^1,5 , Boldyrev V.V. ^1,6 , Vlasov V.V. ^1,4 , Zenkova M.A. ⁴ , Boldyreva E.V. ^1,8

Affiliations

1	Novosibirsk State University, Novosibirsk, Russia
2	Nikolaev Institute of Inorganic Chemistry SB RAS, Novosibirsk, Russia
3	Laboratory of Translational Medicine, Novosibirsk State Medical University, Novosibirsk, Russia
4	Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
5	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Novosibirsk, Russia
6	Institute of Solid State Chemistry and Mechanochemistry SB RAS, Novosibirsk, Russia
7	Institute of Molecular and Cellular Biology SB RAS, Novosibirsk, Russia
8	Boreskov Institute of Catalysis SB RAS, Novosibirsk, Russia

Funding (2)

1	The Ministry of Education and Science of the Russian Federation	Проект 5-100
2	Russian Science Foundation	17-75-20120

Many potential drug candidates are excluded from consideration at the early stages of research and development because of their poor solubility in the biological fluids. Even toxicological tests in vivo become impossible, since there is no way to administer the drug to an animal. The purpose of this study was to explore the feasibility of developing bioavailable formulations of very poorly soluble compounds like soloxolon methyl (water solubility <0.3 μg/ml, 6∙10–13 M). The three-component solid dispersions were prepared by freeze-drying of β-glycine suspensions in a solution of soloxolon methyl and polyethylene glycol in tert-butanol. The β-glycine played the role of a disintegrant, and polyethylene glycol – of a carrier. The cytotoxic activity was tested in vitro with respect to human cervical carcinoma cells; hematological toxicity was tested in vivo on mice. Soloxolon methyl solubility from the formulations increased ∼25–10 times (7.3–3.1 vs 0.3 μg/ml), whereas the half maximal inhibitory concentration decreased 1.3–1.9 times as compared with сrude soloxolon methyl. The in vivo testing has shown the absence of hematological toxicity. The methodology described in this work is transferrable to other poorly water-soluble active pharmaceutical ingredients that cannot be micronized/solubilized by routine techniques in a straightforward way.

Ogienko A.G. , Markov A.V. , Sen'kova A.V. , Logashenko E.B. , Salomatina O.V. , Myz S.A. , Ogienko A.A. , Nefedov A.A. , Losev E.A. , Drebushchak T.N. , Salakhutdinov N.F. , Boldyrev V.V. , Vlasov V.V. , Zenkova M.A. , Boldyreva E.V.
Increasing Bioavailability of Very Poorly Water-Soluble Compounds. A Case Study of an Anti-Tumor Drug, Soloxolon Methyl
Journal of Drug Delivery Science and Technology. 2019. V.49. P.35-42. DOI: 10.1016/j.jddst.2018.10.025 WOS Scopus РИНЦ AN OpenAlex

Submitted:	Sep 5, 2018
Accepted:	Oct 22, 2018
Published online:	Oct 23, 2018
Published print:	Feb 1, 2019

Web of science:	WOS:000457344000005
Scopus:	2-s2.0-85056163945
Elibrary:	38619978
Chemical Abstracts:	2018:2110013
OpenAlex:	W2897845972

DB	Citing
Scopus	6
Web of science	4
Elibrary	5
OpenAlex	6