title: Design and stability study of an oral solution of amlodipine besylate for pediatric patients.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: a.vandervossen@erasmusmc.nl.
authors.forename: A C
authors.initials: AC
authors.lastname: van der Vossen
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: van der Velde
authors.affiliation: Royal Dutch Pharmacists Association (KNMP), PO Box 30460, 2500 GL, Den Haag, The Netherlands.
authors.forename: O S N M
authors.initials: OS
authors.lastname: Smeets
authors.affiliation: Royal Dutch Pharmacists Association (KNMP), PO Box 30460, 2500 GL, Den Haag, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Postma
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands; A15 Pharmacy, Buys Ballotstraat 2, 4207 HT Gorinchem, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Vermes
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: B C P
authors.initials: BC
authors.lastname: Koch
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Vulto
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: L M
authors.initials: LM
authors.lastname: Hanff
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D015195:Drug Design; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D010226:Parabens / Q000737:chemistry; D012996:Solutions; D013395:Sucrose / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D010226:Parabens; D012996:Solutions; D017311:Amlodipine; D013395:Sucrose; C015358:methylparaben
keywords: Amlodipine besylate; Hypertension; Oral solution; Pediatric formulation