Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Universidade Federal de Goiás (UFG), Setor Leste Universitário, Rua 240, Goiânia, GO, 74605-170, Brazil.
Departamento de Farmacología, Farmacia Y Tecnología Farmacéutica, I+D Farma (GI-1645), Faculty of Pharmacy, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Drug Deliv Transl Res. 2024 Jan;14(1):103-115. doi: 10.1007/s13346-023-01385-w. Epub 2023 Aug 9.
This study aims to investigate the effect of the preparation of solid dispersions using supercritical CO (scCO) on the physicochemical properties and the performance of supramolecular gels based on polymer-cyclodextrin (CD) interactions (named poly(pseudo)rotaxanes, PPR) envisaging a transdermal administration. Solid dispersions containing Soluplus, the antihypertensive drug carvedilol (CAR), and CD (αCD or HPβCD) were prepared and characterized by HPLC, XRPD, FTIR, and DSC. PPRs prepared from solid dispersions (SCF gels) and the corresponding physical mixtures (PM gels) were analyzed regarding rheology, morphology, in vitro drug diffusion, and ex vivo drug skin permeation. The application of scCO led to the loss of the crystalline lattice of CAR while preserving its chemical identity. On the contrary, αCD crystals were still present in the SCF solid dispersions. SCF gels were more uniform than their corresponding PM, and the supercritical treatment resulted in changes in the rheological behavior, reducing the viscosity. CAR in vitro diffusion was significantly higher (p < 0.05) for the αCD-based SCF gel than its corresponding PM gel. Drug skin permeation showed a significant increase in drug flux from CD-based SCF gels (containing αCD or HPβCD) compared to corresponding PM gels. Additionally, the pretreatment of the skin with αCD exhibited increased CAR permeation, suggesting an interaction between αCD and the skin membrane. Results evidenced that SCF processing decisively modified the properties of the supramolecular gels, particularly those prepared with αCD.
本研究旨在探讨使用超临界 CO（scCO）制备固体分散体对基于聚合物-环糊精（CD）相互作用的超分子凝胶（命名为聚（伪）轮烷，PPR）的物理化学性质和性能的影响，以期实现经皮给药。含有 Soluplus、抗高血压药物卡维地洛（CAR）和 CD（αCD 或 HPβCD）的固体分散体通过 HPLC、XRPD、FTIR 和 DSC 进行了表征。从固体分散体（SCF 凝胶）和相应的物理混合物（PM 凝胶）制备的 PPR 进行了流变学、形态学、体外药物扩散和体外药物皮肤渗透分析。scCO 的应用导致 CAR 的晶体晶格丢失，但其化学性质得以保留。相反，αCD 晶体仍存在于 SCF 固体分散体中。SCF 凝胶比其相应的 PM 更均匀，超临界处理导致流变行为发生变化，降低了粘度。αCD 基 SCF 凝胶中 CAR 的体外扩散显著更高（p < 0.05）。与相应的 PM 凝胶相比，基于 CD 的 SCF 凝胶（含 αCD 或 HPβCD）的药物皮肤渗透显示出药物通量的显著增加。此外，αCD 预处理皮肤可增加 CAR 的渗透，表明 αCD 与皮肤膜之间存在相互作用。结果表明，SCF 处理显著改变了超分子凝胶的性质，特别是那些用 αCD 制备的凝胶。
