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Isostructural cocrystals of metaxalone with improved dissolution characteristicsстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 1 декабря 2021 г.
- Авторы: Gohel Sunil Kumar, Palanisamy Vasanthi, Sanphui Palash, Prakash Muthuramalingam, Singh Girij Pal, Chernyshev Vladimir
- Журнал: RSC advances
- Том: 11
- Номер: 49
- Год издания: 2021
- Издательство: Royal Society of Chemistry
- Местоположение издательства: United Kingdom
- Первая страница: 30689
- Последняя страница: 30700
- DOI: 10.1039/d1ra05959a
- Аннотация: Muscle relaxant and pain reliever metaxalone (MET) is a biopharmaceutical classification systems (BCS) classII drug with poor aqueous solubility and high permeability. The presence of an aromatic skeleton and cycliccarboxamate moiety are the probable reasons for the decreased aqueous solubility, which impacts on itslow bioavailability. A high dose (800 mg) of the drug often creates adverse side effects on the centralnervous system that needs urgent remedy. Cocrystallization of MET with nicotinamide (NAM),salicylamide (SAM), and 4-hydroxybenzoic acid (HBA) resulted in multicomponent solids that werecharacterized by PXRD, DSC and single crystal X-ray diffraction. Cocrystals with SAM and NAM form 2Disostructural cocrystals, whereas with HBA the result is a differently packed cocrystal hydrate (or anisolehemisolvate) depending upon the crystallization medium. Similar to the reported MET cocrystals, thesecocrystals also confirm the preference for an imide/imide homosynthon in the drug. The dominance ofthe drug–drug homodimer over drug-coformer heterodimers was demonstrated based on bindingenergy calculations. Further, powder dissolution experiments in pH 6.8 phosphate buffer indicate thatthe cocrystals improved the apparent solubility compared to the native drug by 3–9 fold. The absence ofstronger heterosynthons between MET and the coformers, their lower melting points and the highsolubility of the coformers are the probable reasons for the enhanced solubility of the bioactivecomponent. The MET–NAM cocrystal exhibited the highest solubility/dissolution rate among the threebinary solid forms, which may offer improved bioavailability and a lower dose with minimal side effects.
- Добавил в систему: Чернышев Владимир Васильевич