Comparison of drug delivery with autoinjector versus manual prefilled syringe and between three different autoinjector devices administered in pig thigh

Figures & data

Table 1 Study details

Study group (n=4/group)	Needle gauge (Ga) × length (in)	Administration	Evaluation
Study 1: Diazepam Auto-Injector versus Monoject™ manual syringe
P1 P2	22×0.6 autoinjector versus 22×0.6 syringe 20×0.8 autoinjector versus 20×0.8 syringe	Autoinjector in left thigh, manual syringe in right thigh	Dispersion and uptake of injectate
Study group (n=4/group)	Autoinjector comparison	Administration	Evaluation
Study 2: Anapen^® and Twinject^®autoinjectors versus EpiPen^® autoinjector
P1 P2 P3	Anapen 0.3 mL versus EpiPen 0.3 mL Twinject 0.15 mL versus EpiPen^® Jr 0.3 mL Twinject 0.3 mL versus EpiPen 0.3 mL	Each animal was injected with EpiPen in the left thigh and test injector in the right thigh	Dispersion and uptake of injectate

Table 2 Typical functional characteristics of autoinjectors used in Study 1 and Study 2

	Spring forcea (lbs)	Needle extended length (in)b	Needle gauge (Ga)	Dispense time (s)	Activation forcec (lbs)
Diazepam 2 mL	23d	0.51e	22	1.6e	3.6e
Diazepam 2 mL	23d	0.75f	20	1.0f	4.3f
Anapen^® 0.3 mL	2.1g	0.29g	27g	0.78g	2.1g
Twinject^® 0.15 mL	6.5g	0.48g	25g	0.28g	5.6g
Twinject 0.3 mL	6.5g	0.51g	25g	0.63g	5.9g
EpiPen^® 0.3 mL	22.7g	0.59g	22g	0.29g	6.6g
EpiPen^® Jr 0.3 mL	23.6g	0.52g	22g	0.30g	5.7g

Notes:

a Spring force: the force applied to plunger the moment the drug is dispensed;

b needle extended length: the length of the needle that is available to enter the subject’s thigh;

c activation force: the force required to trigger the automated injection;

d diazepam Auto-Injectors use the same spring as the EpiPen, implicating that the spring force will be typically similar;

e certificate of Conformance for Lot RP 452-2, data from Meridian Medical Technologies;

f certificate of Conformance for Lot RP-476-B, data from Meridian Medical Technologies;

g R01-651 Functionality Report, data from Meridian Medical Technologies.

Figure 1 Injectate dispersion volume of diazepam autoinjectors and syringes (Study 1).

Figure 2 Percentage dispersion of injectate at 60 minutes (Study 1).

Figure 3 Percentage uptake versus peak dispersion volume (Study 1).

Table 3 Study 2: injection site skin fat layer measurements

Study comparison and animal	Autoinjector applied to left thigh (Ga × in)	Autoinjector applied to right thigh (Ga × in)	Measured skin/fat depth (mm [in])
			Left thigh (EpiPen^®)	Right thigh (test injector)
Study group P1
Animal 1	Anapen^® 27×0.3	EpiPen 22×0.6	1.86 (0.07)	2.41 (0.10)
Animal 2	Anapen 27×0.3	EpiPen 22×0.6	1.65 (0.07)	2.04 (0.08)
Animal 3	Anapen 27×0.3	EpiPen 22×0.6	1.80 (0.07)	1.91 (0.08)
Animal 4	Anapen 27×0.3	EpiPen 22×0.6	2.64 (0.10)	2.38 (0.09)
Mean ± SD			1.99±0.44 (0.08±0.02)	2.19±0.25 (0.09±0.01)
Study group P2
Animal 1	Twinject^® 25×0.5	EpiPen^® Jr 22×0.5	2.01 (0.08)	1.93 (0.08)
Animal 2	Twinject 25×0.5	EpiPen Jr 22×0.5	2.18 (0.09)	2.51 (0.10)
Animal 3	Twinject 25×0.5	EpiPen Jr 22×0.5	2.24 (0.09)	2.22 (0.09)
Animal 4	Twinject 25×0.5	EpiPen Jr 22×0.5	3.57 (0.14)	2.37 (0.09)
Mean ± SD			2.50±0.72	2.26±0.25
Study group P3
Animal 1	Twinject 25×0.5	EpiPen 22×0.6	1.91 (0.08)	3.27 (0.13)
Animal 2	Twinject 25×0.5	EpiPen 22×0.6	2.09 (0.08)	2.00 (0.08)
Animal 3	Twinject 25×0.5	EpiPen 22×0.6	1.93 (0.08)	2.28 (0.09)
Animal 4	Twinject 25×0.5	EpiPen 22×0.6	2.26 (0.09)	2.35 (0.09)
Mean ± SD			2.05±0.16	2.48±0.55

Abbreviation: SD, standard deviation.

Figure 4 Dispersion volume/target injectate volume ratio over time for autoinjectors (Study 2).