Chemical imaging analysis of active pharmaceutical ingredient in dissolving microneedle arrays by Raman spectroscopy

The purpose of this study was to develop a quality evaluation method for dissolving microneedle arrays (DMNAs) and determine the spatial distribution pattern of drugs in DMNAs. Raman spectroscopy mapping was used to visualize the drug distribution in DMNAs and drug-loaded polymer films as a model. Powder X-ray diffraction (PXRD) and high-pressure liquid chromatography were also performed to characterize DMNAs. Drug-loaded polymer films and DMNAs were prepared by drying the aqueous solutions spread on the plates or casting. PXRD analysis suggested the crystallization of diclofenac sodium (DCF) in several forms depending on its amount in the sodium hyaluronate (HA)-based films. The Raman spectra of HA and DCF showed characteristic and non-overlapping peaks at 1376 and 1579 cm(-1) Raman shifts, respectively. The intensity of the characteristic peak of DCF in the DCF-loaded films increased linearly with the increasing drug content in the range of 4.8 to 16.7% (DCF, w/w). Raman imaging analysis revealed a homogenous dispersion of small DCF crystals in these films. Raman imaging indicates the distribution of DCF on the surface of the DMNA needle. This work highlights the benefit of using Raman spectroscopy mapping to reveal the spatial distribution of drugs in DMNAs.

Automated summary

This study developed a quality evaluation method for dissolving microneedle arrays (DMNAs) and explored the spatial distribution of drugs in DMNAs using Raman spectroscopy mapping. The analysis revealed the crystallization forms of diclofenac sodium (DCF) in the polymer films and the linear relationship between drug content and characteristic peak intensity in the films. Raman imaging demonstrated a homogeneous dispersion of small DCF crystals in the films, as well as the distribution of DCF on the surface of the DMNA needle.