Abstract

The emergence of specific drug–device combination products in the inhalable pharmaceutical industry demands more sophistication of device functionality in the form of an embedded sensing platform to increase patient safety and extend patent coverage. Controlling the nebuliser function at a miniaturised, integrated electrochemical sensing platform with rapid response time and supporting novel algorithms could deliver such a technology offering. Development of a nanoporous gold (NPG) electrochemical sensor capable of creating a unique fingerprint signal generated by inhalable pharmaceuticals provided the impetus for our study of the electrooxidation of salbutamol, which is the active bronchodilatory ingredient in VentolinTM formulations. It was demonstrated that, at NPG-modified microdisc electrode arrays, salbutamol is distinguishable from the chloride excipient present at 0.0154 M using linear sweep voltammetry and can be detected amperometrically. In contrast, bare gold microdisc electrode arrays cannot afford such discrimination, as the potential for salbutamol oxidation and chloride adsorption reactions overlap. The discriminative power of NPG originates from the nanoconfinement effect for chloride in the internal pores of NPG, which selectively enhances the electron transfer kinetics of this more sluggish reaction relative to that of the faster, diffusion-controlled salbutamol oxidation. Sensing was performed at a fully integrated three-electrode cell-on-chip using Pt as a quasi-reference electrode.

Highlights

  • Salbutamol, 2-(tert-butylamino)-1-[4-hydroxy-3-(hydroxymethyl)phenyl] ethanol, is a β2-adrenergic bronchodilator widely used in treating respiratory conditions including bronchial asthma, emphysema, allergen asthma and chronic obstructive pulmonary disease (COPD) [1,2,3]

  • The present study provides insights into the potential of harnessing nanoporous gold (NPG)’s uniqu nanogeometrical properties, enhanced electrocatalytic activity and increased density o low-indexed crystalline planes and high specific surface area NPG to selective discriminate an active pharmaceutical ingredient (API) from its excipients in pharmaceutical formulations

  • The present study provides insights into the potential of harnessing NPG’s unique nanogeometrical properties, enhanced electrocatalytic activity and increased density of lowindexed crystalline planes and high specific surface area NPG to selectively discriminate an API from its excipients in pharmaceutical formulations

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Summary

Introduction

Salbutamol, 2-(tert-butylamino)-1-[4-hydroxy-3-(hydroxymethyl)phenyl] ethanol ( known as Albuterol), is a β2-adrenergic bronchodilator widely used in treating respiratory conditions including bronchial asthma, emphysema, allergen asthma and chronic obstructive pulmonary disease (COPD) [1,2,3]. Salbutamol was originally developed for the treatment of respiratory illness, it has been used to improve lean meat yield in animals by enhancing growth rate and reducing carcass fat [12]. It may accumulate in animal tissues and persist in meat products, with human ingestion of such contaminated foods potentially resulting in acute toxic responses, such as cardiac palpitation, muscle tremors, tachycardia and elevated blood sugar levels [13,14]. There is a clear need to establish rapid, portable and accurate methods to monitor salbutamol, primarily for its treatment of lung disease and due to its illicit use in animal husbandry and subsequent accumulation in water bodies

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