Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The "Meloxicam-Succinic Acid" System as a Case Study

Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The "Meloxicam-Succinic Acid" System as a Case Study Full article

Journal

Crystal Growth and Design
ISSN: 1528-7483 , E-ISSN: 1528-7505

Output data

Year: 2018, Volume: 18, Number: 12, Pages: 7401-7409 Pages count : DOI: 10.1021/acs.cgd.8b01070

Authors

Ogienko Andrey G. , Myz Svetlana A. ^6,7 , Ogienko Anna A. ^2,6 , Nefedov Andrey A. ^3,6 , Stoporev Andrey S. ^1,6,8 , Mel'gunov Maxim S. ^4,6 , Yunoshev Alexander S. ^5,6 , Shalhtshneider Tatyana P. ^6,7 , Boldyrev Vladimir V. ^6,7 , Boldyreva Elena, V ^4,6

Affiliations

1	(Данные Web of science) Russian Acad Sci, AV Nikolaev Inst Inorgan Chem, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Inst Mol & Cellular Biol, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Sci, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk 630090, Russia
4	(Данные Web of science) Russian Acad Sci, GK Boreskov Inst Catalysis, Novosibirsk 630090, Russia
5	(Данные Web of science) Russian Acad Sci, Lavrentev Inst Hydrodynam, Siberian Branch, Novosibirsk 630090, Russia
6	(Данные Web of science) Novosibirsk State Univ, Dept Nat Sci, Novosibirsk 630090, Russia
7	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Solid State Chem & Mechanochem, Novosibirsk 630128, Russia
8	(Данные Web of science) Gubkin Univ, Dept Phys & Colloid Chem, Moscow 119991, Russia

Co-crystals of pharmaceutical compounds are widely used to improve the properties of drug formulations, such as dissolution behavior, bioavailability, or tabletability. The main methods of their synthesis include co-crystallization from solution, melt, or cogrinding. Only a few examples have been documented when co-crystals have been obtained by freeze-drying, namely, in systems where the components of a target co-crystal had similar aqueous solubilities. This work illustrates the potential of freeze-drying for obtaining pharmaceutical cocrystals when the solubilities of individual components differ drastically. Co-crystals of a model system-meloxicam and succinic acid-could be obtained both as a pure crystalline phase and forming a solid dispersion with a polymeric carrier. We show that even for pharmaceutical compounds with very low aqueous solubility, co-crystals with well-soluble coformers can be successfully produced under well-optimized conditions of cooling and subsequent freeze-drying. The rate of release of meloxicam from the fine solid dispersion of its cocrystal with succinic acid in polyethylenglycol obtained by freeze-drying was significantly higher than dissolution rates of (a) pure meloxicam cocrystals with succinic acid obtained by different variants of freeze-drying (thin film freezing, TFF, and spray freeze-drying, SFD), (b) the powder of meloxicam co-crystal with succinic acid obtained by liquid-assisted cogrinding. The possibility to obtain co-crystals of components with very different aqueous solubilities not only by TFF or SFD techniques but also by freezing solutions in vials at temperatures significantly higher than that of liquid nitrogen is shown.

Ogienko A.G. , Myz S.A. , Ogienko A.A. , Nefedov A.A. , Stoporev A.S. , Mel'gunov M.S. , Yunoshev A.S. , Shalhtshneider T.P. , Boldyrev V.V. , Boldyreva E.V.
Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The "Meloxicam-Succinic Acid" System as a Case Study
Crystal Growth and Design. 2018. V.18. N12. P.7401-7409. DOI: 10.1021/acs.cgd.8b01070 WOS Scopus РИНЦ

Published print:

Dec 5, 2018

Web of science	WOS:000452694000020
Scopus	2-s2.0-85056595068
Elibrary	38630292
OpenAlex	W2898673605