Laboratório de Sistemas Poliméricos e Supramoleculares (LSPS), Instituto de Física e Química, Universidade Federal de Itajubá (UNIFEI), Itajubá, 37500-903 MG, Brazil.
Laboratório de Química Computacional (LaQC), Instituto de Física e Química, Universidade Federal de Itajubá (UNIFEI), Itajubá, 37500-903 MG, Brazil.
Int J Pharm. 2018 Jun 10;544(1):203-212. doi: 10.1016/j.ijpharm.2018.04.036. Epub 2018 Apr 18.
Supramolecular structures based on cyclodextrins have been extensively used for drug delivery systems over decades. However, combining host and guest molecules in a pharmaceutical formulation is not a trivial process, being one of the majors concern the inclusion complex compatibility with other excipients presented in the final formulation. Herein, experimental and theoretical calculations were used to investigate the competition of sodium dodecyl sulfate (SDS) with atenolol (ATE) or losartan (LOS), antihypertensive drugs widely used in the treatment of hypertension. Our findings, using nuclear magnetic resonance and isothermal titrations calorimetry experiments and molecular dynamic simulations demonstrated that LOS remain included into CD cavity after excipient (SDS) addition, which was not verified for ATE ternary system, being the drug displaced by SDS molecule.
几十年来,基于环糊精的超分子结构已被广泛用于药物传递系统。然而,将主客体分子结合到药物制剂中并非易事,其中一个主要关注点是包含复合物与最终制剂中存在的其他赋形剂的兼容性。在此,通过实验和理论计算研究了十二烷基硫酸钠(SDS)与用于治疗高血压的降压药阿替洛尔(ATE)或氯沙坦(LOS)之间的竞争。我们的研究结果表明,使用核磁共振和等温滴定量热实验以及分子动力学模拟,即使在添加赋形剂(SDS)后,LOS 仍保留在 CD 腔中,而对于 ATE 三元体系则未得到验证,因为 SDS 分子取代了药物。