Optimizing the Dissolution and Diffusion Characteristics of Ganciclovir through Salt Formation

Shajan, D.K.; Srivastava, A.; Chernyshev, V.V.; Sanphui, P.

Авторы: Shajan Daliya K., Srivastava Anubha, Chernyshev Vladimir V., Sanphui Palash
Журнал: Crystal Growth and Design
Том: 25
Номер: 24
Год издания: 2025
Издательство: American Chemical Society
Местоположение издательства: United States
Первая страница: 10627
Последняя страница: 10636
DOI: 10.1021/acs.cgd.5c01509
Аннотация: Ganciclovir (GCV) is a guanine nucleosideanalogue with potent activity against cytomegalovirus used inmanaging severe infections in immunocompromised patients. It is abiopharmaceutical classification system (BCS) class III medication,exhibiting high aqueous solubility but limited membranepermeability, which restricts its absorption in the intestinalmembrane. This investigation aimed to identify biologicallycompatible salts of GCV to enhance its diffusion characteristicsthrough salt formation with aliphatic dicarboxylic acids, namely,oxalic acid (OXA) and maleic acid (MLE). The synthesizedorganic salts were subjected to solid-state characterization,including powder X-ray diffraction (PXRD), differential scanningcalorimetry, and thermogravimetric analysis, as well as Fourier-transform infrared spectroscopy. Rietveld refinement of the PXRD data provided detailed crystal structures, confirming protontransfer from the carboxylic acid groups of the coformers to the N3 atom of the imidazole ring within the guanine moiety of thedrug. The GCV−MLE salt was obtained as an anhydrous form, whereas GCV−OXA crystallized as a sesquihydrated salt. Stabilitystudies based on ground-state optimization energies indicated that GCV−OXA possessed superior stability compared with bothGCV−MLE and the native drug. Consistently, both salt forms demonstrated notable physicochemical stability for more than onemonth under controlled conditions of 35 ± 5 °C and 75 ± 5% relative humidities. Evaluation of the solubility and diffusion of thesalts, along with the marketed forms of GCV and GCV sodium salt in phosphate buffer (pH 6.8) revealed marked improvements,with aqueous solubility increasing by up to 2-fold and permeation flux enhanced by as much as 5-fold relative to the parent drug.These enhancements are ascribed to the ionic interactions between GCV and the respective salt former. Furthermore, the improveddiffusion profiles of the GCV salts show a positive correlation with their augmented solubility, elevated distribution coefficients,pronounced concentration gradients, and increased polarity conferred by the selected salt coformers.
Добавил в систему: Чернышев Владимир Васильевич

	ИСТИНА	Войти в систему Регистрация
	ИСТИНА ПсковГУ
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

ИСТИНА ПсковГУ

Optimizing the Dissolution and Diffusion Characteristics of Ganciclovir through Salt Formationстатья

Прикрепленные файлы