Namjoshi Sarika N, Telaprolu K C, Grice Jeffrey E, Benson Heather A E, Raney S G, Roberts Michael S, Mohammed Yousuf H
Therapeutics Research Centre, Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia.
Curtin Medical School, Curtin University, Perth, WA, Australia.
Pharm Res. 2024 Dec;41(12):2391-2401. doi: 10.1007/s11095-024-03797-w. Epub 2024 Dec 9.
Typical clinical "in use" conditions for topical semisolids involve their application as a thin film, often with rubbing that can induce metamorphic stress. Yet, product quality and performance tests often characterize the manufactured product, and may not consider product metamorphosis (e.g., shear history) during dispensing and administration. This work sought to elucidate how such metamorphosis might alter product quality and performance.
We evaluated the effect of "in use" stresses on drug crystal metamorphosis in acyclovir creams by optical microscopy. The amount of dissolved acyclovir was determined by separation of the cream base by ultra-centrifugation and quantification by HPLC. IVPT was undertaken on Zovirax US and Aciclostad comparing static and "in use" application of a finite dose. A mechanistic IVPT study was also conducted to understand the influence of acyclovir particle size reduction by "in use" rubbing on skin permeation.
Reduction in acyclovir particle size was seen after "in use" rubbing with increases in the amount of dissolved acyclovir after rubbing (30 and 60 s) compared to static for both products. "In use" application resulted in significantly higher acyclovir permeation from both products. The mechanistic IVPT study proved the role of product metamorphosis.
These results highlight the role of metamorphosis of product microstructure and its influence on performance.
局部用半固体制剂典型的临床“使用中”条件包括将其作为薄膜涂抹，通常伴有摩擦，这可能会引起变形应力。然而，产品质量和性能测试往往是对制成的产品进行表征，可能未考虑产品在调配和给药过程中的变形（如剪切历史）。这项研究旨在阐明这种变形如何改变产品质量和性能。
我们通过光学显微镜评估了“使用中”应力对阿昔洛韦乳膏中药物晶体变形的影响。通过超速离心分离乳膏基质并采用高效液相色谱法定量来测定溶解的阿昔洛韦的量。对美国的阿昔洛韦乳膏（Zovirax）和阿昔洛韦软膏（Aciclostad）进行了体外透皮试验（IVPT），比较了有限剂量的静态和“使用中”涂抹情况。还进行了一项机理体外透皮试验研究，以了解“使用中”摩擦导致的阿昔洛韦粒径减小对皮肤渗透的影响。
与两种产品的静态情况相比，“使用中”摩擦后阿昔洛韦粒径减小，且摩擦后（30秒和60秒）溶解的阿昔洛韦量增加。“使用中”涂抹使两种产品的阿昔洛韦渗透均显著更高。机理体外透皮试验研究证明了产品变形的作用。
这些结果突出了产品微观结构变形的作用及其对性能的影响。
