X-Message-Number: 15864
Date: Wed, 14 Mar 2001 20:19:02 -0800 (PST)
From: Doug Skrecky <>
Subject: comparitive hemolytic activity of solvents

Comparitive hemolytic activity of undiluted organic water-miscible
solvents for intravenous and intra-arterial injection.

PDA J Pharm Sci Technol 55(1): 16-23 Jan-Feb 2001

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
water-soluble 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 phamaceutical formulations for the intravenous
and intra-arterial routes and for embolic materials, 13 water-miscible
organic solvents currently used (diluted with water) for pharmaceutical
applicaitons, werre 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
(polyethyene glycol 200, acetone), moderately hemolytic solvents
(tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal,
ethanol, Soketal, glycofurol) and solvents with low hemolytic activity
(propylene glycol, dimethyl isosorbide, diglyme).

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