title: Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets.
abstract: METHODS
  In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets.
  
  
  OBJECTIVE
  To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis.
  
  
  METHODS
  Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.
  
  
  RESULTS
  All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings.
  
  
  CONCLUSIONS
  In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.
authors.affiliation: Mahidol University-Oxford Tropical Medicine Research Programme, Faculty of Tropical Medicine, Mahidol University, Rajthevee, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pouplin
authors.affiliation: Mahidol University-Oxford Tropical Medicine Research Programme, Faculty of Tropical Medicine, Mahidol University, Rajthevee, Bangkok, Thailand.
authors.forename: Pham Nguyen
authors.initials: PN
authors.lastname: Phuong
authors.affiliation: Mahidol University-Oxford Tropical Medicine Research Programme, Faculty of Tropical Medicine, Mahidol University, Rajthevee, Bangkok, Thailand.
authors.forename: Pham Van
authors.initials: PV
authors.lastname: Toi
authors.affiliation: Mahidol University-Oxford Tropical Medicine Research Programme, Faculty of Tropical Medicine, Mahidol University, Rajthevee, Bangkok, Thailand.
authors.forename: Julie
authors.initials: J
authors.lastname: Nguyen Pouplin
authors.affiliation: Centre for Tropical Medicine, Oxford University Clinical Research Unit Vietnam, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000592:standards; D004338:Drug Combinations; D006801:Humans; D007538:Isoniazid / Q000032:analysis* / Q000627:therapeutic use; D011718:Pyrazinamide / Q000032:analysis* / Q000627:therapeutic use; D011786:Quality Control; D012293:Rifampin / Q000032:analysis* / Q000627:therapeutic use; D013607:Tablets; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
chemical_list: D004338:Drug Combinations; D013607:Tablets; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin