Increasing bioavailability of very poorly water-soluble compounds. A case study of an anti-tumor drug, soloxolon methyl

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	(Данные Web of science) Novosibirsk State Univ, Ul Pirogova 2, Novosibirsk 630090, Russia
2	(Данные Web of science) SB RAS, Nikolaev Inst Inorgan Chem, Novosibirsk, Russia
3	(Данные Web of science) Novosibirsk State Med Univ, Lab Translat Med, Novosibirsk, Russia
4	(Данные Web of science) SB RAS, Inst Chem Biol & Fundamental Med, Lavrentiev Ave 8, Novosibirsk 630090, Russia
5	(Данные Web of science) SB RAS, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk, Russia
6	(Данные Web of science) SB RAS, Inst Solid State Chem & Mechanochem, Novosibirsk, Russia
7	(Данные Web of science) SB RAS, Inst Mol & Cellular Biol, Novosibirsk, Russia
8	(Данные Web of science) SB RAS, Boreskov Inst Catalysis, Novosibirsk, Russia

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 mu g/ml, 6.10-13 M). The three-component solid dispersions were prepared by freeze-drying of beta-glycine suspensions in a solution of soloxolon methyl and polyethylene glycol in tert-butanol. The beta-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 similar to 25-10 times (7.3-3.1 vs 0.3 mu g/ml), whereas the half maximal inhibitory concentration decreased 1.3-1.9 times as compared with crude 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

Published print:

Feb 1, 2019

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