TY - JOUR
T1 - Evaluating parameters affecting drug fate at the intramuscular injection site
AU - McCartan, Adam
AU - Curran, David
AU - Mrsny, Randy
N1 - Funding Information:
Adam McCartan is a recipient of EPSRC funding (grant EP/P510403/1 ) with GSK as a co-funder.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/8/10
Y1 - 2021/8/10
N2 - Intramuscular (IM) injections are a well-established method of delivering a variety of therapeutics formulated for parenteral administration. While the wide range of commercial IM pharmaceuticals provide a wealth of pharmacokinetic (PK) information following injection, there remains an inadequate understanding of drug fate at the IM injection site that could dictate these PK outcomes. An improved understanding of injection site events could improve approaches taken by formulation scientists to identify therapeutically effective and consistent drug PK outcomes. Interplay between the typically non-physiological aspects of drug formulations and the homeostatic IM environment may provide insights into the fate of drugs at the IM injection site, leading to predictions of how a drug will behave post-injection in vivo. Immune responses occur by design after e.g. vaccine administration, however immune responses post-injection are not in the scope of this article. Taking cues from existing in vitro modelling technologies, the purpose of this article is to propose “critical parameters” of the IM environment that could be examined in hypothesis-driven studies. Outcomes of such studies might ultimately be useful in predicting and improving in vivo PK performance of IM injected drugs.
AB - Intramuscular (IM) injections are a well-established method of delivering a variety of therapeutics formulated for parenteral administration. While the wide range of commercial IM pharmaceuticals provide a wealth of pharmacokinetic (PK) information following injection, there remains an inadequate understanding of drug fate at the IM injection site that could dictate these PK outcomes. An improved understanding of injection site events could improve approaches taken by formulation scientists to identify therapeutically effective and consistent drug PK outcomes. Interplay between the typically non-physiological aspects of drug formulations and the homeostatic IM environment may provide insights into the fate of drugs at the IM injection site, leading to predictions of how a drug will behave post-injection in vivo. Immune responses occur by design after e.g. vaccine administration, however immune responses post-injection are not in the scope of this article. Taking cues from existing in vitro modelling technologies, the purpose of this article is to propose “critical parameters” of the IM environment that could be examined in hypothesis-driven studies. Outcomes of such studies might ultimately be useful in predicting and improving in vivo PK performance of IM injected drugs.
KW - Drug fate
KW - Extracellular matrix
KW - Intramuscular injection
KW - Modelling
UR - http://www.scopus.com/inward/record.url?scp=85114385819&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2021.06.023
DO - 10.1016/j.jconrel.2021.06.023
M3 - Article
SN - 0168-3659
VL - 336
SP - 322
EP - 335
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -