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.
May 02, 2008
Volume 32, Issue 5

Dimethyl sulfoxide (DMSO) has long been recognized as an important reaction solvent for the synthesis of drug compounds and is becoming increasingly important as an excipient in finished pharmaceutical dosage forms. The powerful solvating properties of DMSO, coupled with a favorable and well-documented toxicological profile, have encouraged formulation scientists to develop applications in topical, transdermal, and other parenteral drug delivery technologies. DMSO is currently approved as an active pharmaceutical ingredient (API) and is being evaluated as an API in several orphan-status drugs worldwide.

Many pharmaceutical formulators are surprised to learn that a number of regulated products currently available include DMSO as a component of the finished dose. The commercial availability of a DMSO product (Procipient, Gaylord Chemical Co.), which is manufactured under current good manufacturing practice (CGMP) protocols to conform to US Pharmacopeia (USP) and European Pharmacopeia (PhEur) standards, has spurred this developmental activity.

Dimethyl sulfoxide USP in dosage forms and devices

Worldwide, there are a number of products that use dimethyl sulfoxide USP, PhEur. The established roles that dimethyl sulfoxide USP, PhEur currently plays in approved pharmaceutical products include:
  • Stabilizing product formulations: DMSO may be present in product formulations as a cosolvent intended to keep formulation components in solution.
  • The delivery of medical polymers: polymers such as polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA) may be dissolved in DMSO and administered in solution into the body. In situ precipitation of the polymer, followed by dissipation of DMSO, produces an implant than can serve various purposes. Polymer implants may function to provide structural support in the body or as bioerodible depot systems that release impregnated drug substances in a controlled fashion.
  • Sustained-release applications: Dimethyl sulfoxide USP, PhEur has been a carrier solvent in subcutaneously implanted delivery systems. Precise delivery of the therapeutic agent is controlled by osmotic technology.
  • Transdermal penetration enhancement: Using DMSO in concentrations of 70% or greater has been shown to improve the penetration of agents across the skin. At present, all products approved using this DMSO functionality are approved outside of the United States.
  • Cryopreservative: When water and DMSO are blended, a eutectic mixture results, which causes a significant depression of the freezing point of water. When mixed at 50% w/w, the solution remains liquid at –80 °C, preventing cellular damage when preserving cells.
  • Active pharmaceutical ingredient: There is a long established application wherein DMSO has functionality as an active ingredient in the treatment of interstitial cystitis.

Marketed products containing dimethyl sulfoxide USP

The earliest accounts of DMSO use in therapeutic applications were published in the early 1960s, and great interest in this material as a pharmacologic agent occurred throughout that decade. Although investigational new drug (IND) status was granted for DMSO in 1963, concerns about its safety temporarily resulted in a FDA ban on studies using human subjects in 1965 (1, 2)

During the following 15 years, FDA relaxed its policies concerning human investigations with DMSO. This process culminated in an abandonment of its policy to regulate DMSO research in 1980 (3) and the first preparation containing DMSO was approved for marketing in the US in 1978.

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