ВЛИЯНИЕ СОЛЮБИЛИЗАТОРОВ РАЗЛИЧНОГО ТИПА НА ФАРМАКОЛОГИЧЕСКИ ЗНАЧИМЫЕ СВОЙСТВА СИЛИБИНИНА
Аннотация
Цель данной работы состояла в in vitro определении влияния различных классов солюбилизаторов на растворимость и мембранную проницаемость силибинина. Силибинин - лекарственное соединение природного происхождения, обладающее широким спектром терапевтической активности. Он используется в лечении сердечно-сосудистых и ряда онкологических заболеваний. Несмотря на перспективность применения силибинина, он имеет низкие показатели биодоступности из-за плохой растворимости в воде. В связи с этим, в данной работе проведен поиск путей повышения растворимости силибинина. Растворимость силибинина была определена в присутствии солюбилизаторов различной природы (поливинилпирролидон, гидроксипропил-β-циклодекстрин, плюроник F127 и додецилсульфат натрия). Обнаружено, что плюроник F127 и гидроксипропил-β-циклодекстрин являются наиболее эффективными солюбилизаторами. Включение силибинина в мицеллы плюроника и в макроциклическую полость циклодекстрина способствует улучшению растворимости в водной среде. Методом механоактивации были получены твердые дисперсии силибинина с гидроксипропил-β-циклодекстрином с улучшенными показателями растворимости. С помощью диффузионной ячейки Франца были определены коэффициенты мембранной проницаемости силибинина через целлюлозную мембрану. Как было установлено, мембранная проницаемость силибинина в присутствии солюбилизаторов уменьшается. Это может быть обусловлено взаимодействиями, происходящими в растворе между молекулами лекарственного соединения и солюбилизатора. Несколько более выраженное понижение коэффициентов проницаемости для мицеллярных систем с плюроником и додецилсульфатом натрия обусловлено также повышением вязкости растворов. Циклодекстрины и неионогенные ПАВ проявляют наиболее сильно выраженное солюбилизирующее действие по отношению к силибинину, обусловленное, соответственно, образованием водорастворимых комплексов включения и проникновением лекарственного соединения в мицеллы ПАВ.
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