Stability study of a clonidine oral solution in a novel vehicle designed for pediatric patients

Abstract

Clonidine hydrochloride is administered to opioid-addicted mothers’ neonates to reduce neonatal abstinence syndrome. It is prescribed off-label to neonates at 0.5–1 µg/kg/6 h, alone or in combination. The commercially injectable form of clonidine—Catapressan^® 0.15 mg/mL—is being orally given after an appropriate dilution in water. However, this practice is not suitable for a perfectly safe and accurate administration. The objectives were to design a 10 µg/mL oral solution of clonidine hydrochloride in Inorpha^® and to study the stability of this solution by a validated stability-indicating liquid chromatography (LC) method. The chemical, physicochemical and microbiological stability of the compounded formulation stored at 5 ± 3 °C and 25 ± 2 °C was tested over 60 days. The LC method used is specific, linear, accurate and precise. Upon storage between 2 and 8 °C according to classical and ‘in use’ schedules, the concentrations of clonidine and potassium sorbate (preservative) were found to be between 90.0 and 110.0% of the initial concentration, the pH between 4.4 and 4.7 and no microbial growth was noted. The stability of clonidine hydrochloride oral solution in Inorpha^® sets the basis for individualized, easy and safe administration of clonidine in pediatric populations.

Keywords:

• Neonatal abstinence syndrome
• clonidine hydrochloride
• pediatric formulation
• oral solution
• liquid chromatography
• stability study

Acknowledgements

We would like to thank Dr Sophie Ménétré, Head of the Pharmaco-Technical Unit, for preparing clonidine hydrochloride in Inorpha^® solution. We warmly thank Dr A. Lodi, Head of the EDQM Laboratory, for his careful and attentive review of the article. We are grateful to Mr. Franck Blaise for his technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.