Abstract
Commercially manufactured wet/dry autoinjectors containing atropine in solution and powdered HI-6 were evaluated using HPLC for consistency of drug delivery with various solvation times and stability of drugs postsolvation at a temperature of 40°C. Three configurations of autoinjector were tested. System A (SYS A), with a specified mixing time of 5 sec, delivered a volume of 3.0 ml containing 1.86 mg of atropine sulfate and 443 mg of the bispyridinium oxime HI-6 dichloride. System Bl (SYS Bl) and System B2 (SYS B2), with specified mixing times of 40 sec, delivered volumes of 2.3 ml containing 2.13 and 2.06 mg atropine citrate and 424 and 545 mg HI-6 dichloride, respectively. Average coefficients of variation for SYS A were 3.4% for atropine and 5.8% for HI-6 and for SYS Bl and B2 were 5.2% for atropine and 7.0% for HI-6 determinations. Stored from 3 to 14 days at 40°C after the autoinjector contents were mixed, SYS A delivered 1.77 mg atropine sulfate and SYS Bl and B2 delivered 2.02 mg atropine citrate. The delivery of HI-6 dichloride decreased with a half-life of 34 days for SYS A, 39 days for SYS Bl, and 32 days for SYS B2. This resulted in a decrease to 90% of the respective day 0 amount after 4 (SYS A) or 5 (SYS Bl or B2) days.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
FM-8-285 Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries. Departments of The Army, The Navy, and The Air Force, February 1990.
F. R. Sidell. Soman and sarin: Clinical manifestations and treatment of accidental poisoning by organophosphates. Clin. Tox. 7(1):1–17 (1974).
T. A. Loomis and B. Salafsky. Antidotal action of pyridinium oximes in anticholinesterase poisoning; Comparative effects of soman, sarin, and neostigmine on neuromuscular function. Toxicol. Appl. Pharmacol. 5:685–701 (1963).
B. Boskovic, The treatment of soman poisoning and its perspectives. Fund. Appl. Toxicol. 1:203–213 (1981).
B. Boskovic, V. Kovaceuic, and D. Jovanovic. PAM-2 Cl, HI-6, and HGG-12 in soman and tabun poisoning. Fund. Appl. Toxicol. 4:S106–S115 (1984).
J. G. Clement. HI-6: Reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat. Biochem. Pharmacol. 31(7):1283–1287 (1982).
J. G. Clement and P. A. Lockwood. HI-6, an oxime which is an effective antidote of soman poisoning: A structure-activity study. Toxicol. Appl. Pharmacol. 64:140–146 (1982).
J. G. Clement. Efficacy of mono-and bis-pyridinium oximes versus soman, sarin, and tabun poisoning in mice. Fund. Appl. Toxicol. 3:533–535 (1983).
P. Eyer and W. Hell. Chemical stability of the Hagedorn oximes HGG-12 and HI-6. Arch. Pharm. 318:938–946 (1985).
P. Eyer, W. Hell, A. Kawan, and H. Klehr. Studies on the decomposition of the oxime HI-6 in aqueous solution. Arch. Toxicol. 59:266–271 (1986).
P. Fyhr, M. Nicklasson, K. Gunnvald, and A. Brodin. A preformulation study on the kinetics of HI-6 in concentrated solution. Int. J. Pharm. 40:193–200 (1987).
J. G. Clement, K. J. Simons, and C. J. Briggs. Effect of poisoning by soman (pinacolyl methylphosphonofluoridate) on the serum half-life of the cholinesterase reactivator HI-6 in mice. Biopharm. Drug Disposit. 9:177–186 (1988).
B. L. Van der Waerden. Mathematische Statistik, Springer, Berlin, 1957, p. 340.
C. I. Bliss. Statistics in Biology, McGraw-Hill, New York, 1967, Chap. 13.
J. L. Lach, D. R. Flanagan, and L. E. Matheson. Solution stability of the cholinesterase reactivator oxime HI-6. Final Report, Study Number 18, DAMD-17-79-C-9136, April 1984 (AD#B109861L).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schlager, J.W., Dolzine, T.W., Stewart, J.R. et al. Operational Evaluation of Three Commercial Configurations of Atropine/HI-6 Wet/Dry Autoinjectors. Pharm Res 8, 1191–1194 (1991). https://doi.org/10.1023/A:1015818821686
Issue Date:
DOI: https://doi.org/10.1023/A:1015818821686