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

Daisuke Ando,Eiichi Yamamoto,Tamaki Miyazaki,Ken-Ichi Izutsu,Tatsuo Koide

doi:10.1007/s13346-021-01052-y

Daisuke Ando, Eiichi Yamamoto + Show 3 more

Open Access

https://doi.org/10.1007/s13346-021-01052-y

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Abstract

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 1579cm-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.

Highlights

The transdermal drug delivery system (TDDS) is an attractive alternative to conventional drug delivery methods of oral administration or injection
The preparation of dissolving microneedle arrays 3 (DMNAs) by using certain dissolving biodegradable materials, such as hyaluronic acid [6], chondroitin sulfate [8], and carboxymethylcellulose [9], as base polymers are considered as promising methods over other types of MNAs, owing to the lower risk of broken needle tip being left in the skin [10], lower production costs, better stability of loaded active pharmaceutical ingredients (APIs) [11, 12], one-step application, and ability to control the drug release profile [13]
In contrast to the crystallization observed in the films with a concentration greater than 4.8%, where fine crystals grew from a significant number of nuclei, the crystals in the 2.4% film grew from a limited number of nuclei

Summary

Introduction

The transdermal drug delivery system (TDDS) is an attractive alternative to conventional drug delivery methods of oral administration or injection. TDDS offers a variety of advantages, including feasible controlled delivery or sustained release of drugs, avoiding first-pass hepatic metabolism, and a patient-friendly approach [1]. MNAs are minimally invasive drug delivery systems that painlessly pierce the stratum corneum (SC) to enhance molecular transdermal transport. The preparation of DMNAs by using certain dissolving biodegradable materials, such as hyaluronic acid [6], chondroitin sulfate [8], and carboxymethylcellulose [9], as base polymers are considered as promising methods over other types of MNAs, owing to the lower risk of broken needle tip being left in the skin [10], lower production costs, better stability of loaded active pharmaceutical ingredients (APIs) [11, 12], one-step application, and ability to control the drug release profile [13]

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