Release Rate Studies of 5-Aminosalacylic Acid Coated with Atomic Layer-Deposited Al2O3 and ZnO in an Acidic Environment

ACS Appl Bio Mater. 2023 Jan 16;6(1):93-103. doi: 10.1021/acsabm.2c00750. Epub 2022 Dec 14.

Abstract

5-Aminosalicylic acid (5-ASA) is a first-line defense drug used to treat mild cases of inflammatory bowel disease. When administered orally, the active pharmaceutical ingredient is released throughout the gastrointestinal tract relieving chronic inflammation. However, delayed and targeted released systems for 5-ASA to achieve optimal dose volumes in acidic environments remain a challenge. Here, we demonstrate the application of atomic layer deposition (ALD) as a technique to synthesize nanoscale coatings on 5-ASA to control its release in acidic media. ALD Al2O3 (38.0 nm) and ZnO (24.7 nm) films were deposited on 1 g batch powders of 5-ASA in a rotatory thermal ALD system. Fourier transform infrared spectroscopy, scanning electron microscopy, and scanning/transmission electron microscopy establish the interfacial chemistry and conformal nature of ALD coating over the 5-ASA particles. While Al2O3 forms a sharp interface with 5-ASA, ZnO appears to diffuse inside 5-ASA. The release of 5-ASA is studied in a pH 4 solution via UV-vis spectroscopy. Dynamic stirring, mimicking gut peristalsis, causes mechanical attrition of the Al2O3-coated particles, thereby releasing 5-ASA. However, under static conditions lasting 5000 s, the Al2O3-coated particles release only 17.5% 5-ASA compared to 100% release with the ZnO coating. Quartz crystal microbalance-based etch studies confirm the stability of Al2O3 in pH 4 media, where the ZnO films etch 41× faster than Al2O3. Such results are significant in achieving a nanoscale coating-based drug delivery system for 5-ASA with controlled release in acidic environments.

Keywords: 5-aminosalicylic acid; atomic layer deposition; inflammatory bowel disease; quartz crystal microbalance; release rate studies.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Drug Delivery Systems
  • Humans
  • Inflammation
  • Mesalamine
  • Microscopy, Electron, Scanning
  • Zinc Oxide*

Substances

  • Zinc Oxide
  • Mesalamine