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

Parenteral products approved in the US. The earliest product approved in the US was RIMSO-50 (recently acquired by BionichePharma USA, LLC). The product is indicated for the symptomatic relief of patients with interstitial cystitis, a condition involving inflammation of the bladder wall (4). It is a sterile, nonpyrogenic aqueous DMSO formulation (50% w/w DMSO aqueous solution) supplied in 50-mL bottles. RIMSO-50 is instilled directly into a patient's bladder using an aseptic syringe or a catheter and is allowed to remain in the bladder for 15 min before discharge.

Bayer Healthcare Pharmaceuticals(Leverkusen, Germany) has released Viadur, a subcutaneously implanted device that uses DMSO as a solubilizing excipient, for the treatment of prostate cancer (5). The device is implanted in the upper arm and must be removed when a 12-month treatment course has completed. Alza's Duros technology is used to administer leuprolide acetate in a sustained fashion over 12 months. This device contains a solution of dimethyl sulfoxide USP (104 mg) and leuprolide acetate (72 mg) and represents an alternative to other implanted depot delivery systems.

With regard to injectable products, there is currently one application listed in FDA's Center for Drug Evaluation and Research (CDER) inactive ingredient database (6). The product is intended for administration by intravenous infusion. The dosage form of this product is described as "powder, for injection suspension, lyophilized." The amount of DMSO in this product is not described.

There are two device applications referenced by FDA's Center for Devices and Radiological Health (CDRH). These applications are similar in that they use DMSO as a solubilizing excipient to deliver a medical polymer (ethyl vinyl alcohol copolymer, EVOH) into the body to provide a structural benefit. The first of these device products (Onyx, EV3 Inc.) is a liquid embolic system intended for use in the brain as a treatment of brain arteriovenous malformations (7). The medical polymer is injected as a DMSO solution, containing either 6 or 8% EVOH copolymer, at a controlled rate into the bloodstream. As the DMSO dissolves in the bloodstream, a polymeric embolus forms that contains a micronized contrast agent. The other device Tegress (C.R. Bard) serves as bulking agent in the urethra. The action is similar to the Onyx product by means of in situ precipitation of injected DMSO-EVOH copolymer solution in the body (8) .

One product referenced for topical application is listed in the CDER inactive ingredients database and is described as a topical dressing (6). The maximum potency of DMSO is 16.5 mg. A number of other topical or transdermal products that include DMSO are under FDA review for approval at the time of this writing.

Oral products approved in the US. No approved applications have been developed in the US that incorporate DMSO as a component of an orally administered product. DMSO is essentially nontoxic when ingested, having an oral single-dose LD-50 value of 17.4–28.3 g/kg (rat) (9). The low chronic and acute oral toxicity may offer pharmaceutical formulators a delivery option for difficult-to-dissolve medications.

Products for animal health approved in the US. Currently there are two products approved for veterinary use in the US. Domoso is indicated for use in horses for acute swelling and is prepared both as a liquid and gel formulation (10). Domoso is 90% DMSO. Synotic contains 60% DMSO and 0.01% fluocinolone acetonide and is approved for otic treatment in canines (10).

Cryopreservation. Dimethyl sulfoxide USP, Ph Eur has long been appreciated as a media for the cryopreservation of bone marrow and blood components. DMSO is an example of a substance "that would be generally acceptable" as a cryoprotectant for use in human cells, tissues, and cellular and tissue-based products (HCT/Ps), as defined by FDA (11). HCT/Ps intended for use in human recipients are regulated by the Center for Biologics Evaluation and Research (CBER). Among the applications referenced by CBER is an HIV test kit (Nuclisense HIV-1QT) (12). Dimethyl sulfoxide USP is widely used in United States for the cryopreservation of hematopoietic stem cells supplied from umbilical cord blood at childbirth. Cord blood can be used to treat certain genetic disorders (i.e., acute lymphoblastic leukemia) that affect the blood and immune system by means of allogenetic or autologous injection.

DMSO-containing products marketed outside the US. In Europe, there are several topical products in which DMSO acts as an excipient. One of these uses an antiviral (idoxuridine) in the treatment of herpes zoster (13). A second product is approved for use in Canada and in the European Union for the topical treatment of certain types of joint pain.

In Germany, DMSO was approved on an over-the-counter basis for sports-related injuries as Dolicur (Schering AG) and provisions exist in the Russian republics that allow for DMSO self medication (14). DMSO is widely used in China for self-medicated topical pain relief.


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