Gransolve DMI Application Guide
Benzoyl Peroxide Formulations:Dimethyl isosorbide (DMI) has demonstrated exceptional benefits in formulations containing benzoyl peroxide, that are used primarily in the treatment of acne vulgaris, cutaneous fungal infections and poison ivy.
- DMI is an excellent solvent for benzoyl peroxide and is chemically stable to its oxidizing effects
- DMI actually improves the stability of benzoyl peroxide in aqueous media [1,2]
- DMI improves the performance of benzoyl peroxide in at least two ways:
- It prevents the crystallization of benzoyl peroxide during the evaporation of the formulation in the skin, thereby increasing the skin retention time and efficacy.
- It reduces the skin irritation effects of the benzoyl peroxide .
Active Delivery in Skin Care:DMI has been shown to solubilize and enhance performance of many different topical skin actives besides benzoyl peroxide, including benzocaine , pyruvic acid , ferulic acid , methyl salicylate and salicylic acid , acetylsalicylic acid (aspirin) , nicardipine hydrochloride , 5-aminolevulinic acid , potassium nitrate (in combination with water for the desensitization of teeth) , hydrocortisone, dexamethasone and tretinoin (transretinoic acid) , dihydroxyacetone , metaxalone , methocarbamol and meprobamate , tetracyclines , cyclosporins , triamcinolone acetonide, halcinonide, progesterone, testololactone, econazole nitrate, miconazole and nystatin , erythromycin [21, 22], neomycin, indomethacin , ibuprofen, flurbiprofen and naproxen , dibenzylidene sorbitol , isosorbide mononitrate and dinitrate , diazepam , minoxidil, prednisone and estradiol , betamethasone , phenylephrine hydrochloride and tetrahydrozoline hydrochloride , betulinic acid  and many other active ingredients of limited water solubility such as vitamins A, D, and E, cholesterol.
In aqueous systems, the optimum solubilizing effect of DMI with most active ingredients has been found to be at a mole ratio of 1:2 (DMI:water) . This is probably due to the fact that DMI has two hydrogen bonding sites, each of which is capable of complexing a molecule of water. On a weight basis this translates to approximately 5:1 (DMI:water). However, the optimum skin penetration of the active often occurs when the active is solubilized in a mixed solvent system and not at the maximum solubilization in the formulation. Actually, Wiechers et al. have shown that the active should be close to its solubility limit in the formulation to increase the thermodynamic activity of the active, thus setting up a driving force to move the active out of the formulation and into the skin .
In addition to its solubilizing benefits for a wide variety of actives, DMI has also been shown in a number of the cases listed above to reduce the skin irritation properties of the active in the formulation, and the efficacy of the active was also reported to be improved in some cases.
Deodorants and Antiperspirants:DMI has been reported to be an effective coupling agent in deodorant gel sticks, and can be used in combination with volatile silicones (e.g., cyclopentasiloxane) and dibenzylidene sorbitol (gelling agent), as well as with antimicrobial agents such as triclosan . In antiperspirants, it has been shown to be an effective replacement for volatile silicones in aluminum zirconium trichlorohydrex glycine-based sticks. In this application, it is claimed that DMI reduced the staining on fabric and improved the skin-feel .
Sunless Tanners:DMI has been found to have several benefits for sunless tanning products. Most of these products are based on the cosmetic tanning agent, dihydroxyacetone (DHA). DHA is a water soluble, but highly crystalline material. DMI has been found to improve color development on the skin both in color intensity and uniformity . This effect is most likely due to the improved spreading by DMI as well as through solubilization of DHA by DMI. Since DMI is relatively non-volatile and an excellent solvent for DHA, it prevents the crystallization of the DHA during evaporation on the skin, increasing the time for effective reaction of DHA with the skin and thereby increasing the development of color. DMI, along with ethoxydiglycol, has been shown to be especially effective in alcohol- and oil-free spray or mist self-tanners, allowing a deeper, more natural tan when compared to lotion or cream-based products . In addition, DMI and ethoxydiglycol have also been shown to be effective in self-tanning formulations in which cyclodextrins have been used to encapsulate the DHA, and thereby reduce the lingering malodors often associated with the use of these products .
Permanent Waving and Hair Removal (Depilatories):DMI has been shown to be an effective solvent for high pH, sulfur-based products such as permanent waves and depilatories. The actives in these products include ammonium thioglycollate, thiolactic acid, cysteine and cysteamine .
Anti-wrinkle and Anti-ageing Products:DMI has been found to be an excellent solubilizer and excipient for anti-wrinkle products based on matrix metalloproteinase (MMP) inhibitors. MMP inhibitors are known to inhibit the degradation of proteins found in the skin including collagen, elastin and other basement membrane and extracellular matrix proteins . In another example, Shah et al. have shown that DMI and ethoxydiglycol are excellent vehicles for an anti-wrinkle composition based on oligopeptides, fulvic acid and colloidal gold, a system designed to stimulate dermal fibroblasts and increase collagen production in the skin . Additionally, DMI has been shown to be an excellent solvent or co-solvent for a variety of anti-ageing ingredients, including L-ascorbic acid when combined with N-methyl pyrrolidone .
Formulating with Dimethyl Isosorbide:As can be seen from the examples cited above, a very wide variety of actives can be formulated using DMI, and a broad range of formulation types can be readily achieved, including spray mists, light emulsions or milks, solutions, ointments, pastes, solids, gels, lotions, creams, transdermal patches, aerosols, towelettes, and many others.
For most skin care applications, the recommended use level for dimethyl isosorbide ranges from 5% to 50% in aqueous systems (e.g., gels, lotions, creams, etc.). For non-aqueous systems (e.g., ointments, soft solids, etc.), the use level will depend upon the specific active being solubilized or dispersed, and in most cases will range from 40% to 90% of the formulation.
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Restrictions:For skin care applications including rinse-off and leave-on uses, there are no known use level restrictions in the US or EU countries. To date, there has been no CIR report issued on dimethyl isosorbide. In addition, there have been no issued opinions or use level recommendations from the Scientific Committee on Consumer Products (SCCP) or COLIPA. For pharmaceutical applications, the only known use level guidance is that dimethyl isosorbide is listed for topical use in emulsions and creams as an inactive ingredient by the FDA with a maximum dose level of 15% (can be found at the website: www.accessdata.fda.gov/).
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