Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon | Sciact - CRIS-system of Boreskov Institute of Catalysis

Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon Full article

Journal

Pharmaceutics
ISSN: 1999-4923

Output data

Year: 2022, Volume: 14, Number: 3, Article number : 495, Pages count : 16 DOI: 10.3390/pharmaceutics14030495

Tags

formulations for inhalation; formulations for injections; freeze-drying; anti-tuberculosis drugs; clathrate hydrates

Authors

Ogienko Andrey G. ^1,2 , Myz Svetlana A. ² , Nefedov Andrey A. ^1,3 , Ogienko Anna A. ⁴ , Adamova Tatyana P. ⁵ , Voronkova Olga M. ² , Amosova Svetlana V. ⁶ , Trofimov Boris A. ⁶ , Boldyrev Vladimir V. ^1,7 , Boldyreva Elena V. ^1,8

Affiliations

1	Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
2	LLC “SP IIC”, 630049 Novosibirsk, Russia
3	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
4	Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
5	A.V. Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
6	A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia
7	V.V. Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
8	G.K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

Funding (9)

1	Russian Foundation for Basic Research	17-03-00784 (АААА-А17-117040710138-5)
2	Ministry of Science and Higher Education of the Russian Federation	0239-2021-0002
3	Ministry of Science and Higher Education of the Russian Federation	0236-2021-0001
4	Ministry of Science and Higher Education of the Russian Federation	075-00610-21-01 (122011900429-5) FWGZ-2021-0017
5	Federal Agency for Scientific Organizations	V.44.5.6 (01201281994)
6	Internet Initiatives Development Fund
7	Agency for Strategic Initiatives	HealthNet
8	Ministry of Science and Higher Education of the Russian Federation
9	Ministry of Science and Higher Education of the Russian Federation	0238-2021-0005 (АААА-А21-121011490018-2)

There is an urgent need for new drugs in order to overcome the challenge of the ever growingever-growing drug resistance towards tuberculosis. A new highly efficient an-ti-tuberculosis drug, Perchlozone (thioureidoiminomethylpyridinium perchlorate, Pz) is only available as an oral dosage form, though injectable forms and inhalation solutions could be bet-ter alternatives, offering higher bioavailability. In order tTo produce such forms, nano- and mi-cro-particles of APIs need to be prepared as dispersions with carriers. We use this case study, to illustrate the principles of selecting solvents and excipients when preparing such formulations. We justify the choice of water-THF (19.1 wt % THF) as solvent and mannitol as carrier to prepare formulations of Pz – a poorly soluble compound - that are suitable for injections or inhalations. The formulations could be prepared by conventional freeze-drying in vials, making the pro-posed method suitable for industrial scaling. Similar A similar strategy of selecting the organic solvent and the excipient can be applied to other compounds with low water solubility.

Ogienko A.G. , Myz S.A. , Nefedov A.A. , Ogienko A.A. , Adamova T.P. , Voronkova O.M. , Amosova S.V. , Trofimov B.A. , Boldyrev V.V. , Boldyreva E.V.
Clathrate Hydrates of Organic Solvents as Auxiliary Intermediates in Pharmaceutical Research and Development: Improving Dissolution Behaviour of a New Anti-Tuberculosis Drug, Perchlozon
Pharmaceutics. 2022. V.14. N3. 495 :1-16. DOI: 10.3390/pharmaceutics14030495 WOS Scopus РИНЦ AN PMID OpenAlex

Submitted:	Dec 29, 2021
Accepted:	Feb 21, 2022
Published online:	Feb 24, 2022
Published print:	Mar 1, 2022

Web of science:	WOS:000774531600001
Scopus:	2-s2.0-85125641787
Elibrary:	48187443
Chemical Abstracts:	2022:1002369
PMID:	35335870
OpenAlex:	W4214567811

DB	Citing
Scopus	3
Web of science	2
Elibrary	1
OpenAlex	4