Article Text

PDF
INT-005 Development and stability testing of oral clonidine hydrochloride solutions for use in neonatal patients
  1. B Büttner,
  2. AK Stier,
  3. C Lehmann,
  4. P Gärtner,
  5. H Knoth
  1. Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik-Apotheke hospital pharmacy, Dresden, Germany

Abstract

Background Clonidine, a partial α2-adrenergic receptor agonist, has proven to be an effective substance for the therapy of neonatal abstinence syndrome.1 2 The recommended therapeutic dosage is much smaller than the commercially available tablets. Previously published oral liquid preparations contain additives such as parabens, flavourings or substances, which increase viscosity.3 4

Purpose Our purpose was the development and stability testing of oral clonidine hydrochloride solutions with a simple composition for paediatric use, especially for neonatal patients.

Material and methods We developed a stock solution with 200 µg/mL and two ready to use oral solutions containing 20 µg/mL and 10 µg/mL clonidine hydrochloride, preserved with 0.14% potassium sorbate and 0.07% citric acid for pH adjustment. Several batches were stored for 6 months at 25°C; 60% RH, at 40 °C; 75% RH; and in a refrigerator at 2–8°C. Samples were taken after preparation and on days 14, 28, 49, 70, 91 and 161, and stability tests, including a newly validated HPLC method for assay and determination of degradation products, were performed.

Results After 91 days, all refrigerated solutions contained more than 95% clonidine hydrochloride. The stock solution at these storage conditions was stable over at least 161 days with a mean content of 95.5%. At 25°C, 60% RH, the preparations were stable for 28 days. After storage for longer than this period, the content declined below the lower limit of 90% clonidine hydrochloride accompanied by an increase in degradation products. A similar pattern was observed at the higher temperature; the oral solutions were stable for only 14 days.

Conclusion In conclusion, we successfully developed oral clonidine hydrochloride solutions 20 µg/mL and 10 µg/mL for use in neonatal patients, which have proven to be stable for 3 months if stored at 2–8°C in a refrigerator. In addition, we applied a stock solution with a stability of at least 6 months under these storage conditions to simplify the preparation process.

References and/or acknowledgements

  1. Bada, et al. Paediatrics2015;(135).

  2. Surran, et al. J Perinatology2013;(33).

  3. Goede, et al. Int J Pharm2012;(433).

  4. Ensom, et al. J Clin Pharmacol2014;(67).

References and/or acknowledgementsNo conflict of interest

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.