Tissue Resistance during Large-Volume Injections in Subcutaneous Tissue of Minipigs.,Pharmaceutical Research

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Tissue Resistance during Large-Volume Injections in Subcutaneous Tissue of Minipigs.
Pharmaceutical Research ( IF 3.5 ) Pub Date : 2020-09-04 , DOI: 10.1007/s11095-020-02906-9
Andrea Allmendinger ₁ , Stefan Fischer ₁

Affiliation

Purpose

Injection devices for administration of biopharmaceuticals enable subcutaneous self-administration by patients. To meet patient specific capabilities, injection forces need to be characterized. We address the open question of whether tissue resistance significantly contributes to overall injection forces, especially for large injection volumes.

Methods

Subcutaneous tissue resistance was systematically quantified for injection volumes up to 11 mL depending on viscosity (1–20 mPa·s) and injection rates (0.025–0.2 mL/s) using Göttingen Minipigs as the animal model. The contribution of an artificially applied external force at the injection site simulating autoinjector needle cover depression was tested between 2.5–7.5 N.

Results

Tissue resistance reached average values of ~120 mbar for injection volumes up to 11 mL independent of viscosity and injection rate, and maximum values of 300 mbar were determined. Artificially applied external forces led to higher values, independent of the absolute applied force — maximum values of 1 bar were obtained when injecting 4.5 mL of the 20 mPa·s solution at an injection rate of 0.1 mL/s with the application of an artificial 5 N force, corresponding to ~450 mbar. All conditions yield defined injection sites suggesting tissue resistance is defined by mechanical properties of the subcutaneous tissue.

Conclusions

We set our results in relation to overall injection forces, concluding that maximum values in tissue resistance may cause challenges during subcutaneous injection when using injection devices.

中文翻译：

小型猪皮下组织大剂量注射时的组织抵抗力。

目的

用于生物药物给药的注射装置使得患者能够皮下自我给药。为了满足患者的特定能力，需要确定注射力。我们提出了一个开放性的问题，即组织阻力是否会显着影响整体注射力，尤其是对于大注射量。

方法

使用GöttingenMinipigs作为动物模型，根据粘度（1–20 mPa·s）和注射速率（0.025–0.2 mL / s），系统地定量了高达11 mL注射量的皮下组织阻力。在2.5-7.5 N之间测试了在模拟自动注射器针头盖压下的注射部位人工施加的外力的贡献。

结果

对于最高11 mL的注射量，其组织阻力达到了〜120 mbar的平均值，而与粘度和注射速率无关，测定的最大值为300 mbar。人工施加的外力导致更高的值，而与绝对施加的力无关—在以人工方式施加5 mL的溶液以0.1 mL / s的速率注射4.5 mL的20 mPa·s溶液时，获得的最大值为1 bar N力，相当于〜450 mbar。所有条件均产生确定的注射部位，表明组织抵抗力由皮下组织的机械性能决定。