INT-005 Development and stability testing of oral clonidine hydrochloride solutions for use in neonatal patients. (25th February 2017)

• Record Type: Journal Article
• Authors: Büttner, B; Stier, AK; Lehmann, C; Gärtner, P; Knoth, H
• Is Part Of: European journal of hospital pharmacy. Volume 24(2017)Supplement 1
• Page Start: A175
• Page End: A175
• Publication Date: 2017-02-25
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2017-000640.386
• Languages: English
• ISSNs: 2047-9956

Abstract

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: Bada, et al. Paediatrics2015;(135). Surran, et al. J Perinatology 2013;(33). Goede, et al. Int J Pharm2012;(433). Ensom, et al. J Clin Pharmacol2014;(67). No conflict of interest