Department of Pharmaceutical Engineering and Drug Delivery Sciences, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Sizuoka-shi, Shizuoka, 422-8526, Japan.
AAPS PharmSciTech. 2022 Apr 21;23(5):119. doi: 10.1208/s12249-022-02276-y.
The present study evaluated the rheological properties of gel formulations composed of the thixotropic peptide amphiphile, palmitoyl-glycine-histidine (Pal-GH), and the thickener, propylene glycol alginate (PGA), to propose a proper approach to design sprayable gel formulations with good spray performance and high retention of a therapeutic agent. The hysteresis loop area (HLA), a conventional index of thixotropy, was determined from the relationship between the shear stress and shear rate of various formulations with different amounts of Pal-GH and PGA. In addition, a new assessment method for characterizing the thixotropy using the initial structure recovery speed was determined based on the time course of the complex modulus (G*) after structural breakdown of the gel formulations. The G* values increased with the increase in the amount of Pal-GH and PGA, indicating that the formulations were not deformable. Additionally, high HLA and high initial structure recovery speed are preferable when selecting a formulation with good spray performance and high retention. As suitable combinations of Pal-GH and PGA could exhibit both high HLA and high initial structure recovery speed, they are promising components for gel formulations to be used as sprayable agents with good spray performance and high retention. The results also suggested that the initial structure recovery speed would reflect the thixotropy for the formulation more appropriately than HLA. Thus, the initial structure recovery speed could be a useful scale for the preparation of sprayable gel formulations.
本研究评估了由触变肽两亲物棕榈酰-甘氨酸-组氨酸（Pal-GH）和增稠剂丙二醇藻酸盐（PGA）组成的凝胶制剂的流变性能，提出了一种合适的方法来设计具有良好喷雾性能和高治疗剂保留率的可喷雾凝胶制剂。滞后环面积（HLA），一种常用的触变性指标，是通过测定不同 Pal-GH 和 PGA 用量的制剂的剪切应力与剪切速率之间的关系来确定的。此外，基于凝胶制剂结构破坏后复构模量（G*）的时程，确定了一种使用初始结构恢复速度来表征触变性的新评估方法。G*值随 Pal-GH 和 PGA 用量的增加而增加，表明制剂不可变形。此外，在选择具有良好喷雾性能和高保留率的制剂时，高 HLA 和高初始结构恢复速度是优选的。由于合适的 Pal-GH 和 PGA 组合可以表现出高 HLA 和高初始结构恢复速度，因此它们是用作具有良好喷雾性能和高保留率的可喷雾制剂的有前途的凝胶制剂成分。研究结果还表明，与 HLA 相比，初始结构恢复速度更能反映制剂的触变性。因此，初始结构恢复速度可能是制备可喷雾凝胶制剂的有用指标。
