Spatial distribution of soluble insulin in pig subcutaneous tissue: Effect of needle length, injection speed and injected volume.
The spatial distribution of a soluble insulin formulation was visualized and quantified in 3-dimensions using X-ray computed tomography. The drug distribution was visualized for ex vivo injections in pig subcutaneous tissue. Pig subcutaneous tissue has very distinct layers, which could be separated in the tomographic reconstructions and the amount of drug in each tissue class was quantified. With a scan time of about 45min per sample, and a robust segmentation it was possible to analyze differences in the spatial drug distribution between several similar injections. It was studied how the drug distribution was effected by needle length, injection speed and injected volume. For an injected volume of 0.1ml and injection depth of 8mm about 50% of the injections were partly intramuscular. Using a 5mm needle resulted in purely subcutaneous injections with minor differences in the spatial drug distribution between injections. Increasing the injected volume from 0.1ml to 1ml did not increase the intramuscular volume fraction, but gave a significantly higher volume fraction placed in the fascia separating the deep and superficial subcutaneous fat layers. Varying the injection speed from 25l/s up to 300l/s gave no changes in the drug concentration distribution. The method presented gives novel insight into subcutaneous injections of soluble insulin drugs and can be used to optimize the injection technique for subcutaneous drug administration in preclinical studies of rodents.
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark; Niels Bohr Institute, University of Copenhagen, Blegdamsvej, DK-2100 Copenhagen, Denmark. Electronic address: mtmx@novonordisk.com.
Maria
M
Thomsen
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
Christian Hove
CH
Rasmussen
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
Hanne H F
HH
Refsgaard
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
Karen-Margrethe
KM
Pedersen
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
Rikke K
RK
Kirk
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.
Mette
M
Poulsen
Niels Bohr Institute, University of Copenhagen, Blegdamsvej, DK-2100 Copenhagen, Denmark.
Robert
R
Feidenhans'l
D000818:Animals; D007279:Injections, Subcutaneous / Q000295:instrumentation / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009339:Needles; D040521:Subcutaneous Tissue / Q000378:metabolism*; D013552:Swine; D014057:Tomography, X-Ray Computed
D007328:Insulin
Drug distribution; Insulin aspart; Subcutaneous injections; X-ray computed tomography