Design and stability study of an oral solution of amlodipine besylate for pediatric patients.

Abstract

INTRODUCTION:

Amlodipine is an antihypertensive agent recommended for the management of hypertension in children and adolescents. The commercially available tablets of 5 and 10mg do not provide the necessary flexibility in dosing needed for treating children. Our goal was to develop a pediatric oral solution of amlodipine, using a robust manufacturing process suitable for ex-tempora and larger scale production.

METHODS:

The parameters API and preservative content, related substances, appearance and pH were studied under four different storage conditions. Samples were analyzed up to 12months. Microbiological quality was studied in an 18-week in-use test based on a two-times daily dosing schedule.

RESULTS:

The stability of the formulation was influenced by storage conditions and composition. A formulation containing amlodipine besylate, sucrose syrup and methyl paraben remained physically stable for 12months at 4°C with no loss of amlodipine content. Related substances increased during the study but remained below 0.5%. In-use stability was proven up to 18weeks.

DISCUSSION:

Storage under refrigerated conditions was necessary to prevent precipitation and to obtain an acceptable shelf-life. In conclusion, we have developed and validated an amlodipine oral solution, suitable for the pediatric population. This liquid formulation is preferred over manipulated commercial dosage forms or non-standardized extemporaneously compounded formulations.

• Authors: A C van der Vossen, I van der Velde, O S N M Smeets, D J Postma, A Vermes, B C P Koch, A G Vulto, L M Hanff
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 92 Pg. 220-3 (Sep 20 2016) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 27217083 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Antihypertensive Agents
• Parabens
• Solutions
• Amlodipine
• Sucrose
• methylparaben

Topics

• Administration, Oral
• Amlodipine (chemistry)
• Antihypertensive Agents (chemistry)
• Drug Design
• Drug Stability
• Drug Storage
• Humans
• Parabens (chemistry)
• Solutions
• Sucrose (chemistry)