X-Message-Number: 15707
Date: Wed, 21 Feb 2001 08:40:38 -0800 (PST)
From: Doug Skrecky <>
Subject: dimethyl isosorbide looks promising

"The combination of low hemolytic potential, and fast permeation
through skin, suggest dimethyl isosorbide might be worth a look, 
as component of vitrification solutions."


<1 of 2>
  Lysis of human red blood cells in the presence of
  various cosolvents.
  Journal of Parenteral Science and Technology 39(2): 64-68 1985
  Two in vitro methods are presented which enable the evaluation
  of virtually any solution for the production of lysis in
  intramuscular and intravenous administration. These methods
  differ from the standard hemolytic method in that the RBCs
  and ghosts, which remain after mixing test solution with RBCs,
  are washed with normal saline. The intact RBCs are then lysed
  with water. Since the final measurement is always made in pure
  water, the effects of vehicle components on the absorbance or
  solubility of hemoglobin are virtually eliminated. these methods
  were used to evaluate propylene glycol (PG). dimethyl sulfoxide
  (DMSO), ethanol (EtOH), polyethylene glycol 400 (PEG 400),
  dimethyl acetamide (DMA), and dimethyl isosorbide (DMI) for
  hemolytic potential in comparison to a reference of 10% EtOH,
  40% PG, and 50% water. Measured LD 50 values for lysis of RBCs
  are expressed as total volume percent of cosolvent in whole blood.
  These values are: 39.5% DMI, 37.0% DMA, 30% PEG 400, 21.2% EtOH,
  10.3% reference, 5.7% PG, and 5.1% DMSO.

<2 of 2>
  Codiffusion of propylene
  glycol and dimethyl isosorbide in hairless mouse skin.
  European Journal of Pharmaceutics & Biopharmaceutics.  46(3):265-71, 1998
  The in vitro percutaneous fluxes of propylene
  glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide
  (DI) were determined and their effect on nifedipine (N) flux and lag time
  evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured
  in vitro by beta-scintigraphy and N permeation was measured by HPLC under
  finite and infinite dose conditions. Evaluation of each of the solvents
  separately showed that pure DI possessed the inherent ability to traverse the
  skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and
  40% of the DI had permeated across the skin with nearly linear permeation
  between 4 and 18 h and the relative order of permeation was PG > DI > N. DI
  permeation was further aided in the presence of PG and OA. N flux was
  dependent on concomitant solvent permeation. Over a 24-h test period a dose
  dependent response was observed for N, with 4.9-15.6 mg of N delivered from
  the lowest and highest doses, respectively, and the highest dose yielding
  zero-order flux of 146 (g/h per cm2). Copyright 1998 Elsevier Science B.V.

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