Stability evaluation of compounded clonidine hydrochloride oral liquids based on a solid-phase extraction HPLC-UV method

Daphné Coache,Marianne Boulé,Jean-Marc Forest,Mihaela Friciu,Grégoire Leclair,V Gaëlle Roullin,Abdelwahab Omri

doi:10.1371/journal.pone.0260279

Daphné Coache, Marianne Boulé + Show 5 more

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https://doi.org/10.1371/journal.pone.0260279

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Abstract

The present study aimed to assess the stability of clonidine hydrochloride oral liquids (20-μg/mL) prepared from two different generic tablets in Ora-Blend and stored in amber plastic bottles. Physical and chemical stabilities were evaluated over a period of 90 days at 25°C. Analytical challenges were overcome with the development of a new extraction procedure based on solid phase extraction to ensure efficient clonidine hydrochloride quantification. The absence of physical instabilities, evaluated by qualitative and quantitative measurements (static multiple light scattering), as well as the absence of chemical instabilities, evidenced by a stability-indicating HPLC-UV method, confirmed that a beyond-use date of 90 days was appropriate for these compounded oral liquids.

Highlights

IntroductionAn α-2 adrenergic receptor agonist, is indicated for the treatment of hypertension in adults [1]
Clonidine hydrochloride, an α-2 adrenergic receptor agonist, is indicated for the treatment of hypertension in adults [1]
The mortar and pestle were rinsed with two 10-mL portions of Ora-Blend and the oral liquid was completed to the desired final volume (100 mL)

Summary

Introduction

An α-2 adrenergic receptor agonist, is indicated for the treatment of hypertension in adults [1]. Even though clonidine hydrochloride has only been approved by Health Canada for its effects on cardiac output and blood pressure in adults, off-label use in children is not unusual. Clonidine hydrochloride can be used for multiple indications, like neonatal abstinence syndrome, analgesia, sedation, and hypertensive crisis [2]. A slow tapering of clonidine is sometimes needed, for example, in the treatment of neonatal abstinence syndrome or after a long term use of dexmedetomidine, which is an α-2 adrenergic receptor agonist with sedative properties used in intensive care unit [3]. It is really important to have access to a compounded clonidine formulation that will allow a slow tapering of the dose adapted to the pediatric population. Even if tablets of variable strengths are commercially available in Canada (25, 100 and 200 μg), liquid formulations must be compounded by pharmacists since tablets do not allow a precise dose according to the patient weight

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