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Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
Effect of "In Use" Administration on Topical Product Metamorphosis and Skin Permeation of Acyclovir Creams:
Sarika N Namjoshi1, K C Telaprolu1, Jeffrey E Grice1
1Therapeutics Research Centre, Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
These results highlight the role of metamorphosis of product microstructure and its influence on performance.
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