Disodium salt of glycyrrhizic acid - A novel supramolecular delivery system for anthelmintic drug praziquantel

Disodium salt of glycyrrhizic acid - A novel supramolecular delivery system for anthelmintic drug praziquantel Научная публикация

Журнал

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

Вых. Данные

Год: 2019, Том: 50, Страницы: 66-77 Страниц : 12 DOI: 10.1016/j.jddst.2019.01.014

Ключевые слова

Praziquantel; Glycyrrhizic acid; Solubility enhancement; Mechanochemistry; Intermolecular interactions; Micelles; Drug delivery

Авторы

Meteleva Elizaveta S. ¹ , Chistyachenko Yulia S. ¹ , Suntsova Lyubov P. ¹ , Khvostov Mikhail, V ^2,5 , Polyakov Nikolay E. ³ , Selyutina Olga Yu ³ , Tolstikova Tatyana G. ^2,5 , Frolova Tatyana S. ^2,4,5 , Mordvinov Viatcheslav A. ⁴ , Dushkin Alexander, V ^1,6 , Lyakhov Nikolay Z. ¹

Организации

1	(Данные Web of science) Russian Acad Sci, Inst Solid State Chem & Mechanochem, Siberian Branch, Kutateladze St 18, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Vorozhtsov Inst Organ Chem, Siberian Branch, Acad Lavrentiev Av 9, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Sci, Voevodsky Inst Chem Kinet & Combust, Siberian Branch, Inst Skaya St 3, Novosibirsk 630090, Russia
4	(Данные Web of science) Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Acad Lavrentiev Av 1, Novosibirsk 630090, Russia
5	(Данные Web of science) Novosibirsk State Univ, Pirogova St 1, Novosibirsk 630090, Russia
6	(Данные Web of science) Zhejiang Univ Technol, Natl Engn Res Ctr Proc Dev Act Pharmaceut Ingredi, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China

The aim of the study was to enhance the solubility and bioavailability of praziquantel (PZQ) through mechanochemical preparation of its solid compositions with the disodium salt of glycyrrhizic acid (Na(2)GA). The compositions were studied in the solid phase by means of scanning electron microscopy, powder X-ray diffraction and thermal analysis, and in solutions by means of HPLC, gel permeation chromatography, phase solubility assay and H-1 NMR spectroscopy. PZQ permeability was studied by means of parallel artificial membrane permeability assay and with a monolayer of Caco-2 cells. The pharmacokinetic characteristics and acute toxicity of PZQ and its compositions were studied on mice. Solubility of PZQ in the compositions increases up to 3.5 times. The micelles in Na(2)GA solutions possess a molecular mass of similar to 60 kDa. An increase in PZQ solubility may be due to its inclusion into micelles of glycyrrhizic acid. The permeability of PZQ was found to be much higher from its composition with Na(2)GA in comparison with initial PZQ. An increase in PZQ bioavailability by a factor of 3 in laboratory mice and changes of pharmacokinetic curve shape were demonstrated for the oral administration of its composition with Na(2)GA. The solid compositions show high chemical stability under rapid storage test. The obtained PZQ compositions may be a promising basis for the development of anthelmintic preparations with increased efficiency.

Meteleva E.S. , Chistyachenko Y.S. , Suntsova L.P. , Khvostov M.V. , Polyakov N.E. , Selyutina O.Y. , Tolstikova T.G. , Frolova T.S. , Mordvinov V.A. , Dushkin A.V. , Lyakhov N.Z.
Disodium salt of glycyrrhizic acid - A novel supramolecular delivery system for anthelmintic drug praziquantel
Journal of Drug Delivery Science and Technology. 2019. V.50. P.66-77. DOI: 10.1016/j.jddst.2019.01.014 WOS Scopus РИНЦ

Опубликована в печати:

1 апр. 2019 г.

Web of science	WOS:000461717000009
Scopus	2-s2.0-85060074289
РИНЦ	38652288
OpenAlex	W2911135908