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> Title Lysis of human red blood cells in the presence of various cosolvents. Source Journal of Parenteral Science and Technology 39(2): 64-68 1985 Abstract 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> Title Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin. Source European Journal of Pharmaceutics & Biopharmaceutics. 46(3):265-71, 1998 Nov. Abstract 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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=15707