INT-005 Development and stability testing of oral clonidine hydrochloride solutions for use in neonatal patients

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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

No conflict of interest

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