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Dimethyl Sulfoxide USP, PhEur in Approved Pharmaceutical Products and Medical Devices
The authors survey the approved applications of dimethyl sulfoxide USP, PhEur across the healthcare industry and consider the suitability of DMSO from a regulatory and formulation compatibility standpoint.
Table I: Basic physical properties of dimethyl sulfoxide.
Solubility of excipients and API compounds.
Dimethyl sulfoxide USP, PhEur is chemically compatible with many pharmaceutical excipients and APIs. A database providing
solubility data for more than 100 drug compounds and 30 excipients is available on-line (15), dimethyl sulfoxide USP is referenced
in The Handbook of Pharmaceutical Excipients (16). Some basic physical properties of DMSO are listed in Table I.
Table II: Common solubilizing excipient solubilities in dimethyl sulfoxide (solvent).*
DMSO is completely miscible with water, ethanol, propylene carbonate, and propylene glycol. It is practically insoluble–insoluble
in many lipophilic ingredients (e.g., light mineral oil USP, soybean oil NF). Table II provides an overview of solubility
data for dimethyl sulfoxide USP, with common solubilizing excipients.
It is worthwhile to note that water has a dramatic effect on the properties of dimethyl sulfoxide USP, PhEur (17). Although
this may be a useful means to lower the solvent strength of DMSO in limited applications, water contamination in DMSO products
may affect formulation stability in a negative sense if formulation components have a low degree of water solubility. Mixtures
that are high in water content take on the general solvent properties of water. DMSO is fully hydrated at 67 wt% strength
in water (10).
Table III: Common viscosity modifying excipient solubilities in dimethyl sulfoxide.*
Viscosity and rheology modification.
The viscosity of DMSO formulations may be modified using additives that work well in water. Some pharmaceutically acceptable
materials that may be used for this purpose include hydroxypropyl cellulose (Klucel, Hercules Aqualon Corp.), hypromellose USP (Methocel E3 Premium LV, Dow Chemical), carbomers (Carbopol, Noveon Corp.), and methylcellulose USP. Although
such materials have low solubility levels in DMSO (see Table III), very low loading levels are capable of producing high-viscosity
gels.
A standard procedure for producing a thickened solution (~10,000 cPs, depending upon the product used) from a DMSO base follows:
Dimethyl sulfoxide (100 g) is combined with triethanolamine (0.5 g) and is stirred mechanically. Klucel LF (0.5 g) is sifted
into the mixture slowly; hasty addition of Klucel can result in its aggregation into clumps which are difficult to disperse.
It can be helpful to sift the Klucel into the mixture by passing it through a screen. The mixture is stirred at room temperature
for 30 min., at which point no solids are seen to the naked eye.
A.S. McKim is director of technology at Gaylord Chemical Company LLC, 209 Industrial Parkway, Bogalusa, LA 70433, tel. 985.732.6308, fax: 985.732.6317.
Articles by A.S. McKim
Robert Strub
Robert Strub is director of business development at Gaylord Chemical Company LLC.
Articles by Robert Strub
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