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Dear list Members,
a compound orally given to dog as a pure methocel suspension gave a
much lower systemic exposure compared to the same dose formulated
dissolving the compound in DMSO (5% final volume) and then suspending
it in methocel.
The check on particle size from both formulations is ongoing, but I
wonder if somebody could help with info on effect of 5% DMSO on GI
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This may be purely formulation affect. Our experience
in drug discovery shows that suspensions prepared by
dissolving and precipitating the active moiety will
result in higher bioavailability which can be
attributed to a more uniform distribution of
particles.Upto 10% DMSO is allowed by oral route. It
would be of my interest to listen to others'
Sun Pharma, India
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Swaroop Kumar Vakkalanka
(by way of David
>This may be purely formulation affect...>>
The phenomenon of "ferrying" by DMSO of some drugs (e.g., morphine
sulfate, penicillin, steroids including cortisone, and even insulin,
etc.) and other chemicals across several biological membranes is
known for a long time. Unfortunately, the mechanism of this effect is
somehow obscure (several mechanisms were proposed, including magic :-)
One likely mechanism may be a histamine-like vasodilation and
increased absorption by increasing local blood flow:
Adamson, J. E., Crawford, H. H., and Horton, C.E. The action of
dimenthyl sulfoxide on the experimental pedicle flap. Surg. Forum.
Kligman, A.M. Topical pharmacology and toxicology or dimethyl
sulfoxide (DMSO). Part 1. J. Amer. Med. Assoc. 193: 796-804 (1965).
Kligman. A.M. Topical pharmacology and toxicology of dimethyl
sulfoxide (DMSO). Part 2. J. Amer. Med. Assoc. 193: 923-928 (1965).
A short Internet search provided some more or less reliable literature (below).
I hope this will help.
Janusz Z. Byczkowski, Ph.D.,D.Sc.,D.A.B.T.
212 N. Central Ave.
Fairborn, OH 45324
JZB Consulting web site: http://members.aol.com/JanuszB/consult.htm
* In vitro skin penetration study employing guinea pig skin as the
membrane:The exact mechanisms involved in the membrane "penetrant"
action of DMSO have yet to be elucidated:
Elfbaum, S.G., and Laden K. Effect of dimethyl sulfoxide on
percutaneous absorption--a mechanistic study. J. Soc. Cosmet. Chem.
19, 841 (1968) (Abstract).
* The increased percutaneous absorption of 17-estradiol dissolved in
DMSO in the immature female rat:
Djan, T.I., and Gunber, D.L. Percutaneous absorption of two steriods
dissoved in dimethyl surlfoxide in the immature female rat. Ann. N.Y.
Acad. Sci. 141: 406-413 (1967).
* Usefulness of DMSO as a carrier for antitumor agents:
Maddock, C.L., Green, M.N., and Brown, B.L. Topical administration of
anti-tumor agents to locally implanted neoplasma. Proc. Amer. A.
Cancer Res. 7. 46. (1966) (abstract).
* DMSO as a vehicle for topical antiviral agents - increased
penetration of acyclovir (ACV) through guinea pigs skin in vitro:
Spruance, S.L., McKeough, M.B., and Cardinal, J.R. Dimethyl Sulfoxide
as a vehicle for topical antiviral chemotherapy. Ann. N.Y. Acad. Sci.
411: 28-33 (1983).
* The threefold increase percutaneous penetration of hydrocortisone
and testosterone in DMSO:
Maibach, H. I., and Feldmann, R. J. The effect on DMSO of
percutaneous penetration of hydrocortisone and testosterone in man.
Ann. N.Y. Acad. Sci. 141: 423-427 (1967).
* Increased penetration of visual tracers (methylene blue, iodine,
and iron dyes) by DMSO into human skin:
Sulzberger, M.B., Cortese, T.A., Jr., Fishman, L., Wiley, H.S., and
Peyakovich, P.S. Some effects of DMSO on human skin in vivo. Ann N.Y.
Acad. Sci. 141: 437-450 (1967).
* Antibodies to bovine serum albumin developed when a mixture of
DMSO and bovine serum albumin was applied to the skin of rabbits:
Smith, R.E. The use of dimethyl sulfoxide in allergy and immunology.
E.E.N.T. Digest 30: 47-54 (1968).
* Penicillin G potassium, mixed in 90% DMSO, was readily carried
through intact human skin:
Perlman, F., and Wolfe, H.F. Dimethyl Sulfoxide as a penetrant
carrier of allergens through intact human skin. J. Allergy 38:
* Hydrocortisone or hexachlorophene carried by DMSO into the deeper
layers of the stratum corneum:
Stoughton, R.B. Dimethyl sulfoxide (DMSO) induction of a steroid
reservoir in human skin. Arch. Dermatol. 91: 657-660 (1965).
Stoughton, R.B. Hexachlorophene deposidtion in human stratum corneum.
Enhancement by dimethylacetamide. demethylsulfoxide. and
methylethylether. Arch.Dermatol. 94: 646-648 (1966)
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