School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
School of Pharmacy, Universita di Roma Tor Vergata, Rome, Italy.
AAPS PharmSciTech. 2017 Nov;18(8):3219-3226. doi: 10.1208/s12249-017-0795-0. Epub 2017 May 30.
There is extensive literature on in vivo studies with cordycepin, but these studies were generally conducted without validation of the various formulations, especially in terms of the solubility of cordycepin in the dosing vehicles used. Cordycepin is a promising drug candidate in multiple therapeutic areas, and there is a growing interest in studies aimed at assessing the pharmacological activity of this compound in relevant animal disease models. It is likely that many reported in vivo studies used formulations in which cordycepin was incompletely soluble. This can potentially confound the interpretation of pharmacokinetics and efficacy results. Furthermore, the presence of particles in intravenously administered suspension can cause adverse effects and should be avoided. Here, we present the results from our development of simple and readily applicable formulations of cordycepin based on quantitative solubility assessment. Homogeneous solutions of cordycepin were prepared in phosphate-buffered saline (PBS) at different pH levels, suitable as formulations for both intravenously and oral administration. For the purpose of high-dose oral administration, we also developed propylene glycol (PPG)-based vehicles in which cordycepin is completely soluble. The stability of the newly developed formulations was also assessed, as well as the feasibility of their sterilisation by filtration. Additionally, an HPLC-UV method for the determination of cordycepin in the formulations, which may also be useful for other purposes, was developed and validated. Our study could provide useful information for improvement of future preclinical and clinical studies involving cordycepin.
有大量关于蛹虫草素的体内研究文献，但这些研究通常没有对各种制剂进行验证，特别是在蛹虫草素在所用给药载体中的溶解度方面。蛹虫草素是多个治疗领域有前途的候选药物，人们越来越关注旨在评估该化合物在相关动物疾病模型中药理活性的研究。许多报道的体内研究可能使用了不完全溶解蛹虫草素的制剂。这可能会混淆药代动力学和疗效结果的解释。此外，静脉内给予混悬剂中的颗粒会引起不良反应，应予以避免。在这里，我们根据定量溶解度评估，介绍了蛹虫草素简单且易于应用的制剂开发结果。在不同 pH 值的磷酸盐缓冲盐水（PBS）中制备了蛹虫草素的均匀溶液，可作为静脉内和口服给药的制剂。为了进行高剂量口服给药，我们还开发了基于丙二醇（PPG）的载体，其中蛹虫草素完全溶解。还评估了新开发制剂的稳定性，以及通过过滤进行灭菌的可行性。此外，还开发并验证了一种用于制剂中蛹虫草素测定的 HPLC-UV 方法，该方法也可能对其他用途有用。我们的研究可为涉及蛹虫草素的未来临床前和临床研究的改进提供有用信息。
