Abstract
Background: Drug crystallization following application of transdermal and topical formulations may potentially compromise the delivery of drugs to the skin. This phenomenon was found to be limited to the superficial layers of the stratum corneum (~7 µm) in our recent reports and tape stripping of the skin samples was necessary. It remains a significant challenge to profile drug crystallization in situ without damaging the skin samples. Methods: This work reports the application of an X-ray microbeam via synchrotron SAXS/WAXS analysis to monitor drug crystallization in the skin, especially in the deeper skin layers. Confocal Raman spectroscopy (CRS) was employed to examine drug distribution in the skin to complement the detection of drug crystallization using SAXS/WAXS analysis. Results: Following application of saturated drug solutions (ibuprofen, diclofenac acid and salts), CRS depth profiles confirmed that the drugs generally were delivered to a depth of ~15–20 µm in the skin. This was compared with the WAXS profiles that measured drug crystal diffraction at a depth of up to ~25 µm of the skin. Conclusion: This study demonstrates the potential of synchrotron SAXS/WAXS analysis for profiling of drug crystallization in situ in the deeper skin layers without pre-treatment for the skin samples.
| Original language | English |
|---|---|
| Pages (from-to) | 1321-1334 |
| Number of pages | 14 |
| Journal | Expert Opinion on Drug Delivery |
| Early online date | 22 Jul 2020 |
| DOIs | |
| Publication status | Published - 22 Jul 2020 |
Bibliographical note
Publisher Copyright:© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Acknowledgements
The synchrotron radiation experiments were performed at the BL40XU of SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal No. 2014A1173). We would like to express our appreciation to Dr Noboru Ohta for his advice on experimental setup at Spring-8 and on data analysis as well as to Emeritus Professor Jonathan Hadgraft for his advice and supervision.Funding
This work was supported by Ministry of Education Malaysia for PhD funding of Choon Fu Goh. We also acknowledge travel funding provided by the International Synchrotron Access Program (ISAP) managed by the Australian Synchrotron, part of ANSTO, and funded by the Australian Government and the grant number for the synchrotron travel was ISP8044.
Keywords
- confocal Raman spectroscopy
- drug crystallization
- SAXS/WAXS
- Stratum corneum
- synchrotron
ASJC Scopus subject areas
- Pharmaceutical Science