RT Journal Article SR Electronic T1 Development of a Nondestructive Leak Testing Method Utilizing the Head Space Analyzer for Ampoule Products Containing Ethanol-Based Solutions JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 434 OP 444 DO 10.5731/pdajpst.2012.00882 VO 66 IS 5 A1 Hirotaka Sudo A1 Michael O'driscoll A1 Kenji Nishiwaki A1 Yuji Kawamoto A1 Philip Gammell A1 Gerhard Schramm A1 Toni Wertli A1 Heino Prinz A1 Atsuhide Mori A1 Kazuhiro Sako YR 2012 UL http://journal.pda.org/content/66/5/434.abstract AB The application of a head space analyzer for oxygen concentration was examined to develop a novel ampoule leak test method. Studies using ampoules filled with ethanol-based solution and with nitrogen in the headspace demonstrated that the head space analysis (HSA) method showed sufficient sensitivity in detecting an ampoule crack. The proposed method is the use of HSA in conjunction with the pretreatment of an overpressurising process known as bombing to facilitate the oxygen flow through the crack in the ampoule. The method was examined in comparative studies with a conventional dye ingress method, and the results showed that the HSA method exhibits sensitivity superior to the dye method. The results indicate that the HSA method in combination with the bombing treatment provides potential application as a leak test for the detection of container defects not only for ampoule products with ethanol-based solutions, but also for testing lyophilized products in vials with nitrogen in the head space. LAY ABSTRACT: The application of a head space analyzer for oxygen concentration was examined to develop a novel ampoule leak test method. The proposed method is the use of head space analysis (HSA) in conjunction with the pretreatment of an overpressurising process known as bombing to facilitate oxygen flow through the crack in the ampoule for use in routine production. The result of the comparative study with a conventional dye leak test method indicates that the HSA method in combination with the bombing treatment can be used as a leak test method, enabling detection of container defects.