Lucero-Borja Diego, Ruiz Rebeca, Fuguet Elisabet, Ràfols Clara
Departament d'Enginyeria Química i Química Analítica and Institut of Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
Pion Inc. (UK) Ltd., Forest Row Business Park, Forest Row, East Sussex RH18 5DW, UK.
Pharmaceutics. 2025 Apr 25;17(5):571. doi: 10.3390/pharmaceutics17050571.
: The bioavailability of a drug depends, among other parameters, on solubility. One of the strategies used to enhance the solubility of sparingly soluble drugs is the use of excipients. Excipients can interact with the drug by increasing its solubility and/or stabilizing supersaturated solutions. Some of the most common excipients are cyclodextrins and hydrophilic polymers. : The effect of two cyclodextrins (captisol and cavasol) and three hydrophilic polymers (klucel, kollidon and plasdone S630) on the solubility of three ionizable drugs (benzthiazide, isoxicam, and piroxicam) is evaluated at biorelevant pH values, using two complementary techniques. : The solubility enhancement was evaluated by the comparison of the solubility with and without the presence of excipients through the shake-flask and CheqSol methodology. : Captisol and cavasol slightly increase the concentration of the neutral species of the drugs in the solution before precipitation begins, although they do not enhance the supersaturation duration nor the thermodynamic solubility of the drugs. The increase in solubility in the presence of cyclodextrins is mainly caused by the ionization state of the drug. Hydrophilic polymers not only improve thermodynamic solubility but also the extent and the duration of the supersaturation. Some metastable forms are observed for benzthiazide and isoxicam in the presence of kollidon and plasdone S630. : The shake-flask method enabled the evaluation of thermodynamic solubility both in the absence and presence of excipients. Meanwhile, the CheqSol method provided insights into the presence of supersaturated solutions. Different behavior is observed depending on the nature of the excipient.
药物的生物利用度除其他参数外还取决于溶解度。提高难溶性药物溶解度的策略之一是使用辅料。辅料可通过增加药物溶解度和/或稳定过饱和溶液与药物相互作用。一些最常见的辅料是环糊精和亲水聚合物。
使用两种互补技术，在生物相关pH值下评估了两种环糊精（Captisol和Cavasol）和三种亲水聚合物（羟丙基纤维素、聚乙烯吡咯烷酮和聚维酮S630）对三种可电离药物（苄噻嗪、异恶酰胺和吡罗昔康）溶解度的影响。
通过摇瓶法和CheqSol方法，比较有无辅料存在时的溶解度，评估溶解度的提高情况。
Captisol和Cavasol在沉淀开始前会略微增加溶液中药物中性物种的浓度，尽管它们不会延长过饱和持续时间，也不会提高药物的热力学溶解度。环糊精存在时溶解度的增加主要是由药物的电离状态引起的。亲水聚合物不仅能提高热力学溶解度，还能提高过饱和的程度和持续时间。在聚乙烯吡咯烷酮和聚维酮S630存在下，观察到苄噻嗪和异恶酰胺有一些亚稳形式。
摇瓶法能够评估有无辅料时的热力学溶解度。同时，CheqSol方法提供了有关过饱和溶液存在情况的见解。根据辅料的性质观察到不同的行为。
