title: Development and formulation of a 0.2% oral solution of midazolam containing gamma-cyclodextrin.
abstract: In absence of dedicated children formulation, intravenous formulations of midazolam, which exhibit strong bitterness, are occasionally used for oral or sublingual administration. In order to improve the quality and the acceptance by children of a midazolam anesthesia premedication, a new 0.2% (w/v) aqueous solution for oral administration has been prepared. The final formulation was obtained by the adjunction of a sweetener (sucralose), an aroma (orange aroma) and gamma-cyclodextrin to a citric acid solution of midazolam. The gamma-cyclodextrin forms an inclusion complex with the hydrophobic midazolam as evidenced using nuclear magnetic resonance spectroscopy (stoichiometry 1:1, K=283 M(-1)). A sterile filtration method was selected for the formulation microbial preservation using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). Finally, a routine high performance liquid chromatography (HPLC) method is proposed for the quantitative determination of global midazolam amount in the pharmaceutical preparation.
authors.affiliation: Pharmacie Centrale, Centre Hospitalier Universitaire, place Victor Pauchet, F-80054 Amiens, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Marçon
authors.forename: David
authors.initials: D
authors.lastname: Mathiron
authors.forename: Serge
authors.initials: S
authors.lastname: Pilard
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lemaire-Hurtel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Dubaele
authors.forename: Florence
authors.initials: F
authors.lastname: Djedaini-Pilard
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008874:Midazolam / Q000008:administration & dosage / Q000138:chemical synthesis*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000138:chemical synthesis; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000138:chemical synthesis*
chemical_list: D019999:Pharmaceutical Solutions; D047408:gamma-Cyclodextrins; D013395:Sucrose; C026285:trichlorosucrose; C023792:gamma-cyclodextrin; D008874:Midazolam