Abstract
In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly watersoluble drugs. The use of water-miscible nonaqueous solvents is therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies.
The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme).
- hemolysis
- hemocompatibility
- blood
- intravenous
- intra-arterial
- intravascular injection
- water-miscible organic solvents
- parenterals
Footnotes
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.
