Novel cannula design improves large volume auto-injection rates for high viscosity solutions

Abstract

A prototype reusable large-volume (2 mL) autoinjector (LVAI) was designed to compare injection performance of a novel 27 gauge ultra-thin wall (UTW) pre-filled syringe (PFS) cannula (8 mm external cannula length, 14.4 mm total needle length) against an existing 27 gauge special thin wall (STW) PFS cannula (12.7 mm external cannula length, 19 mm total needle length) across a range of injectate viscosities (2.3-30 cP) in a series of in vivo feasibility studies in swine. The UTW cannula had an approximately 30% greater cross-sectional lumen area than the STW cannula. The target exposed needle length was adjusted to ensure appropriate needle penetration depth and achieve injectate deposition in the subcutaneous (SC) tissue. Delivery time and volume, injection site leakage, injectate depot location, and local tissue effects were examined. The STW and UTW cannulae both provided effective SC delivery of contrast placebo solutions, and were able to accommodate injectate viscosity up to 30 cP without quantifiable leakage from the tissue and with minor tissue effects which resolved within 1-2 hours. Delivery times at each viscosity were significantly different between PFS types with the UTW PFS producing faster delivery times. In a histological substudy of the UTW cannula using injectate viscosities up to 50 cP, injection site reactions were rare and, when present, were of minimal severity. This series of studies demonstrates the feasibility of LVAI SC injection and informs autoinjector and PFS design considerations. Use of a UTW cannula may enable more rapid LVAI injections with minimal tissue effects, especially for higher viscosity formulations.

Keywords: Large volume subcutaneous injection; autoinjector; high viscosity; injection depth; in vivo; pre-filled syringe; tissue response; ultra-thin wall cannula.

Figure 1.

Reusable large-volume 2 mL autoinjector prototype. The prototype device design provided a flexible platform to assess delivery performance due to its ability to interchange drive springs, select needle extension length, and replace PFS components post-delivery.

Figure 2.

Fluoroscopic image of the needle in tissue during injection; the device interface with the skin surface and cannula are clearly visualized allowing measurements of needle penetration depth.

Figure 3.

Observed erythema and wheal scores (0–4) by target exposed needle lengths of 4, 6, and 8 mm immediately after 2 mL saline injection. Shorter exposed needle length was associated with higher scores.

Figure 4.

Percent delivered volume by PFS and viscosity. Delivered volumes for each PFS/viscosity combination were within ±5% of filled syringe volume.

Figure 5.

LVAI 2 mL delivery time (seconds) by PFS and viscosity. As expected, delivery time increased with increasing viscosity, and significant differences in delivery time were observed between viscosity levels. Mean delivery times were less than 15 seconds at all tested viscosity levels using the UTW PFS, and at 2.3 and 20 cP using the STW PFS. The UTW PFS produced a significant reduction in delivery time at 20 and 30 cP compared to the STW PFS.

Figure 6.

Representative fluoroscopic images of 2 mL depositions in tissue by viscosity. The surface of the skin is readily evident due to its stark contrast with the air surrounding the animal under the fluoroscope. The injectate depositions appear as dark areas in the image with distinct top and bottom borders. All injectate placebos used for deposition imaging in this study had sufficient radiological density to be readily visible by fluoroscopy. The interface between the dermal and subcutaneous space is also evident in the images, typically 2–3 mm from the surface of the skin.

Figure 7.

Depot top (within colored boxes) and bottom border measurements (mean ± SD) per PFS and viscosity. All deliveries were confirmed within the SC tissue via fluoroscopic imaging. The 0.0 y-axis represents the skin surface.

Figure 8.

Percentage of observed erythema (left) and edema (right) scores (0–4) for tested device configurations immediately after injection and at T-60 minutes and T-120 minutes, stratified by viscosity. T-120 minute observations for the UTW PFS deliveries were unnecessary as complete resolution occurred by T-60 minutes. Injection site effect resolution occurred within 1–2 hours post 2 mL injections. T-60 observations were not made for STW cannula injections.