title: Design and stability study of a paediatric oral solution of methotrexate 2 mg/ml.
abstract: Oral paediatric forms development by pharmaceutical industry is still insufficient. The present study was performed to propose an adapted and pleasant formulation of liquid oral formulation of MTX. The solution is composed of injectable methotrexate, water, Ora Sweet(®) and sodium bicarbonate. After 120 days storage, pH remained stable at about 8 in all formulations, insuring no risk of MTX precipitation. MTX content in solution formulation, determined by high performance liquid chromatography measurements, remained in the specifications of >90% of the initial concentration when stored at 4 and 25°C. Forced degradation of MTX by heat and acidic conditions allowed formation and detection of degradation products by the analytical method. Microbial study of the preparation shows that the solution remains in the specifications during all the storage, or after one sample each week during one month, eventually indicating the microbial properties are not affected by patient use. To conclude, we here propose a new MTX liquid formulation stable for at least 120 days.
authors.affiliation: Pharmacie Centrale, Centre Hospitalier Universitaire d'Angers, Angers, Cedex, France. Electronic address: sandy.v@laposte.net.
authors.forename: Sandy
authors.initials: S
authors.lastname: Vrignaud
authors.affiliation: Pharmacie Centrale, Centre Hospitalier Universitaire d'Angers, Angers, Cedex, France; L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Briot
authors.affiliation: Pharmacie Centrale, Centre Hospitalier Universitaire d'Angers, Angers, Cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Launay
authors.affiliation: Laboratoire de Bactériologie, Institut de Biologie en Santé-PBH, Centre Hospitalier Universitaire d'Angers, Angers, Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Kempf
authors.affiliation: Pharmacie Centrale, Centre Hospitalier Universitaire d'Angers, Angers, Cedex, France; L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lagarce
mesh_terms: D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001419:Bacteria / Q000254:growth & development; D002626:Chemistry, Pharmaceutical; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D015195:Drug Design; D004355:Drug Stability; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000008:administration & dosage*; D010372:Pediatrics; D019999:Pharmaceutical Solutions; D013649:Taste
chemical_list: D000964:Antimetabolites, Antineoplastic; D019999:Pharmaceutical Solutions; D008727:Methotrexate
keywords: HPLC; Methotrexate; Oral paediatric solution; Stability study