Abstract
Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady’s Children’s Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80–81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations.
Highlights
IntroductionExtemporaneous oral liquid preparations are formulated by pharmacists when there is no commercially available dosage form for adjustable dosing or appropriate dosage form for pharmaceutical care of paediatric patients, elderly patients and patients with specific conditions [1,2]
Losartan was the first angiotensin II receptor blocker (ARB) approved for paediatric hypertension by the U.S Food & Drug Administration (FDA) in 2004, in response to regulatory initiatives for paediatric clinical trials, by the FDA and the European Medicines
Losartan reference standard subjected to forced degradation under oxidation conditions (3% v/v H2 O2 for 7 days in the dark at room temperature (RT)) and analysed by high performance liquid chromatography (HPLC)
Summary
Extemporaneous oral liquid preparations are formulated by pharmacists when there is no commercially available dosage form for adjustable dosing or appropriate dosage form for pharmaceutical care of paediatric patients, elderly patients and patients with specific conditions [1,2]. The physical, chemical, and microbiological properties must be considered when formulating extemporaneous preparations, as these can impact on dose uniformity, stability, and storage conditions [4]. The drug is orally active and is available in tablet form in doses ranging from 12.5 to 100 mg for administration in adults. Losartan was the first ARB approved for paediatric hypertension by the U.S Food & Drug Administration (FDA) in 2004, in response to regulatory initiatives for paediatric clinical trials, by the FDA and the European Medicines
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