title: Measuring tissue back-pressure--in vivo injection forces during subcutaneous injection.
abstract: OBJECTIVE
  Limited information is available on injection forces of parenterals representing the in vivo situation. Scope of the present study was to investigate the contribution of the subcutaneous (sc) tissue layer to injection forces during in vivo injection.
  
  
  METHODS
  Göttingen minipigs received injections of isotonic dextran solutions (1-100 mPas) into the plica inguinalis using different injection rates and volumes (0.025-0.2 mL/s and 2.5 vs. 4.5 mL).
  
  
  RESULTS
  The contribution of the sc back-pressure to injection forces was found to increase linearly with viscosity and injection rate ranging from 0.6 ± 0.5 N to 1.0 ± 0.4 N (1 mPas), 0.7 ± 0.2 N to 2.4 ± 1.9 N (10 mPas), and 1.8 ± 0.6 N to 4.7 ± 3.3 N (20 mPas) for injection rates of 0.025 to 0.2 mL/s, respectively. Variability increased with viscosity and injection rate. Values are average values from 10 randomized injections. A maximum of 12.9 N was reached for 20 mPas at 0.2 mL/s; 6.9 ± 0.3 N was determined for 100 mPas at 0.025 mL/s. No difference was found between injection volumes of 2.5 and 4.5 mL. The contribution of the tissue was differentiated from the contribution of the injection device and a local temperature effect. This effect was leading to warming of the (equilibrated) sample in the needle, therefore smaller injection forces than expected compensating tissue resistance to some parts.
  
  
  CONCLUSIONS
  When estimating injection forces representative for the in vivo situation, the contribution of the tissue has to be considered as well as local warming of the sample in the needle during injection.
authors.affiliation: Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Allmendinger
authors.forename: Robert
authors.initials: R
authors.lastname: Mueller
authors.forename: Edward
authors.initials: E
authors.lastname: Schwarb
authors.forename: Mark
authors.initials: M
authors.lastname: Chipperfield
authors.forename: Joerg
authors.initials: J
authors.lastname: Huwyler
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation; D004867:Equipment Design; D007279:Injections, Subcutaneous; D008297:Male; D011312:Pressure; D012212:Rheology; D012867:Skin / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D003911:Dextrans