title: Pharmaceutical development and optimization of azithromycin suppository for paediatric use.
abstract: Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought.
authors.affiliation: Univ. Bordeaux, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, Bordeaux, France. tina.kauss@u-bordeaux2.fr
authors.forename: Tina
authors.initials: T
authors.lastname: Kauss
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gaubert
authors.forename: Chantal
authors.initials: C
authors.lastname: Boyer
authors.forename: Boubakar B
authors.initials: BB
authors.lastname: Ba
authors.forename: Muriel
authors.initials: M
authors.lastname: Manse
authors.forename: Stephane
authors.initials: S
authors.lastname: Massip
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Léger
authors.forename: Fawaz
authors.initials: F
authors.lastname: Fawaz
authors.forename: Martine
authors.initials: M
authors.lastname: Lembege
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Boiron
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Pascal
authors.initials: P
authors.lastname: Millet
authors.forename: Karen
authors.initials: K
authors.lastname: Gaudin
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017963:Azithromycin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D013488:Suppositories; D014329:Tropical Climate
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D013488:Suppositories; D011092:Polyethylene Glycols; D017963:Azithromycin