Allmendinger Andrea, Mueller Robert, Schwarb Edward, Chipperfield Mark, Huwyler Joerg, Mahler Hanns-Christian, Fischer Stefan
Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
Pharm Res. 2015 Jul;32(7):2229-40. doi: 10.1007/s11095-014-1611-0. Epub 2014 Dec 24.
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.
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).
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.
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.
关于代表体内情况的注射剂注射力的信息有限。本研究的范围是调查皮下（sc）组织层在体内注射过程中对注射力的贡献。
使用不同的注射速率和体积（0.025 - 0.2 mL/s以及2.5与4.5 mL），将等渗右旋糖酐溶液（1 - 100 mPas）注射到哥廷根小型猪的腹股沟皱襞中。
发现皮下背压对注射力的贡献随着粘度和注射速率的增加呈线性增加，对于0.025至0.2 mL/s的注射速率，分别从0.6±0.5 N（1 mPas）增加到1.0±0.4 N，从0.7±0.2 N（10 mPas）增加到2.4±1.9 N，从1.8±0.6 N（20 mPas）增加到4.7±3.3 N。变异性随着粘度和注射速率的增加而增加。这些值是10次随机注射的平均值。在0.2 mL/s时，20 mPas的情况下达到最大12.9 N；在0.025 mL/s时，100 mPas的情况下测定为6.9±0.3 N。2.5 mL和4.5 mL的注射体积之间未发现差异。组织的贡献与注射装置的贡献以及局部温度效应区分开来。这种效应导致针内（平衡后的）样品升温，因此比预期更小的注射力补偿了部分组织阻力。
在估计代表体内情况的注射力时，必须考虑组织的贡献以及注射过程中针内样品的局部升温。
