Dimethyl Sulfoxide USP, PhEur in Approved Pharmaceutical Products and Medical Devices - Pharmaceutical Technology

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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.


Pharmaceutical Technology


Perhaps the most widely held concern around the safety of DMSO is that it "can take everything through the skin." Although it is true that DMSO itself can penetrate skin and does enhance the penetration rates of some chemical compounds (31), no solvent has the universal ability to fully negate the barrier properties of human skin. Indeed, it is not widely recognized that all dipolar aprotic solvents have this ability to some extent, and that N-methylpyrollidone is essentially as effective as DMSO in terms of skin penetration (32). Moreover, when water is present as a cosolvent in the formulation, the penetration kinetics of DMSO are greatly diminished. Unlike other solvents, DMSO itself is largely harmless when applied dermally; the LD-50 dermal value for DMSO is quite high (40 g/kg, rat) (9). The larger issue is its ability to facilitate dermal transport of unwanted materials into the body.

In a general sense, large molecular-weight entities (e.g., polymers, proteins) are unlikely to undergo penetration enhancement when applied in DMSO solution (32, 33). Likewise, DMSO does not uniquely accelerate the absorption of all small-molecule chemical classes (33). In many cases , some assumptions may be made to chemically analogous materials that have been tested for this effect. For situations in which safety is a concern, appropriate tests (e.g., in vitro Franz Cell evaluations, animal study) should be considered to ascertain whether DMSO plays any role in enhancing unwanted dermal penetration of formulation components.

Lastly, some have expressed concern about the garlic- or onion-like taste and odor experienced by patients who have ingested DMSO or have had DMSO applied to their skin. This side effect is attributable to a specific DMSO metabolite: dimethyl sulfide (DMS), a component of natural onion and garlic flavors. The low toxicity level of this compound is further exemplified by its inclusion in the US Food Chemical Codex, and as a synthetic flavoring substance and adjuvant (CFR 21 section 172.515) in the United States (12).

Conclusion

Once a medical curiosity, dimethyl sulfoxide (DMSO) is now incorporated into a number of regulated products for healthcare and drug delivery applications. Perhaps the most important features of DMSO as an excipient include its use to stabilize formulated products and its ability to solubilize many difficult-to dissolve materials.

A GMP-produced compendial product (Procipient dimethyl sulfoxide, PhEur) is now commercially available for pharmaceutical applications. This ensures that a pharmaceutically acceptable product which is suitable for use in human applications is reliably attainable.

Regardless of past history, dimethyl sulfoxide USP, PhEur is a versatile and safe material that has much to offer as an excipient product. The number of regulated pharmaceutical products and delivery systems that contain dimethyl sulfoxide USP, PhEur has increased in recent years, and it appears that the positive trends supporting this product will continue.

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. Robert Strub is director of business development at Gaylord Chemical Company LLC.

*To whom all correspondence should be addressed.

Submitted: Oct. 22, 2007. Accepted: Dec. 5, 2007.


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