Therapeutics Research Centre, Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
School of Pharmacy, The University of Queensland, Woolloongabba, QLD, 4102, Australia.
Pharm Res. 2024 Oct;41(10):2043-2056. doi: 10.1007/s11095-024-03772-5. Epub 2024 Sep 30.
The objective of this study was to investigate whether different dispensing processes can alter the physicochemical and structural (Q3) attributes of a topical cream product, and potentially alter its performance.
Acyclovir cream, 5% (Zovirax®) is sold in the UK and other countries in a tube and a pump packaging configurations. The structural attributes of the cream dispensed from each packaging configuration were analyzed by optical microscopy, confocal Raman microscopy and cryo-scanning electron microscopy. Rheological behavior of the products was also evaluated. Product performance (rate and extent of skin delivery) was assessed by in vitro permeation tests (IVPT) using heat-separated human epidermis mounted in static vertical (Franz-type) diffusion cells.
Differences in Q3 attributes and IVPT profiles were observed with creams dispensed from the two packaging configurations, even though the product inside each packaging appeared to be the same in Q3 attributes. Visible globules were recognized in the sample dispensed from the pump, identified as dimethicone globules by confocal Raman microscopy. Differences in rheological behaviour could be attributed to these globules as products not dispensed through the pump, demonstrated a similar rheological behaviour. Further, IVPT confirmed a reduced rate and extent to delivery across human epidermis from the product dispensed through a pump.
Different methods of dispensing topical semisolid products can result in metamorphosis and Q3 changes that may have the potential to alter the bioavailability of an active ingredient. These findings have potential implications for product developers and regulators, related to the manufacturing and comparative testing of reference standard and prospective generic products dispensed from different packaging configurations.
本研究旨在探讨不同的配药过程是否会改变局部乳膏产品的物理化学和结构（Q3）特性，并可能改变其性能。
在英国和其他国家，阿昔洛韦乳膏（5%，Zovirax®）以管装和泵装两种包装形式销售。通过光学显微镜、共聚焦拉曼显微镜和冷冻扫描电子显微镜分析从每种包装形式分配的乳膏的结构属性。还评估了产品的流变行为。通过在装有热分离人表皮的静态垂直（Franz 型）扩散细胞中进行体外渗透测试（IVPT），评估产品性能（皮肤传递的速率和程度）。
尽管每个包装内的产品在 Q3 属性上似乎相同，但从两种包装形式分配的乳膏观察到 Q3 属性和 IVPT 曲线的差异。从泵分配的样品中可识别出可见的小球，通过共聚焦拉曼显微镜鉴定为二甲硅油小球。流变行为的差异可能归因于这些小球，因为未通过泵分配的产品表现出相似的流变行为。此外，IVPT 证实通过泵分配的产品在穿过人表皮时的传递速率和程度降低。
不同的局部半固体产品配药方法会导致形态变化和 Q3 变化，这可能会改变活性成分的生物利用度。这些发现对产品开发人员和监管机构具有潜在影响，涉及不同包装形式分配的参考标准和潜在仿制药的制造和比较测试。
