Dimethyl Sulfoxide (DMSO) is widely used in the pharmaceutical industry. DMSO is required throughout the segment for applications in drug discovery, API synthesis, analytical applications and an excipient solvent in pharmaceutics. We produce material which addresses the quality and regulatory requirements for the specific use.
Dimethyl Sulfide (DMS) also finds use as its sulfonium salt (in epoxidation reactions) or in borane reducing agents (BH3-DMS). It also has applications in API synthesis as a reagent in reactions such as epoxidation and hydroboration-oxidation.
Procipient®(Dimethyl Sulfoxide USP, Ph. Eur.) used in topical and parenteral drug delivery. Details of DMSO in approved products can be located in the U.S. Food and Drug Administration-Center for Drug Evaluation and Research’s database Inactive Ingredient Search for Approved Drug Products.
Procipient®(Dimethyl Sulfoxide USP, Ph. Eur.) has been recognized for many years as a topical penetration enhancer. Both human and animal health applications currently exist which use DMSO in this role. Solvent properties of DMSO may be beneficial in that higher loading of the API in semisolid products can sometimes be achieved. The low vapor pressure of DMSO enables formulation to absorb without the skin-chilling effect of excipients such as alcohol.
From a formulation standpoint, DMSO viscosity is similar to water and DMSO can serve as a way to lower formulation viscosity. The addition of traditional thickening agents (Carbopol®, Klucel®, Methocel®, Tylose®) can be a way to increase DMSO viscosity allowing for optimally designed dosage forms.
Approved applications for this route of administration exist for Dimethyl Sulfoxide USP where it provides solubility to the API. Worldwide many innovative applications are currently being evaluated for small volume parenteral products and vaccines.
Emerging applications include autologous cell processing and the delivery (or processing) of carbohydrates using a compendial DMSO product. DMSO may also act as a process aid for biopolymers used in parenteral dosage forms.
As an API
DMSO is approved throughout the world as an API (Active Pharmaceutical Ingredient) for the treatment of Interstitial Cystitis. The approved formulation is a sterile 50% aqueous DMSO solution that is instilled into the bladder.
While this is the only approved indication for DMSO in North America DMSO, it is used on other parts of the world as a topical anti-inflammatory in addition to traditional self-medication applications.
Various instrumental methods require consistent solvents with well characterized impurity profiles. DMSO can be used in analytical applications and excels due to the wide range of materials DMSO will dissolve.
DMSO is used in UV and IR spectroscopy for the analysis of polymers, inorganic and organic compounds. DMSO can also be used as a solvent in the preparation of samples for HPLC analysis and is especially useful a ‘universal solvent’ for poorly soluble drugs.
HTS / Compound Storage
DMSO exhibits outstanding solvent capability for both organic and inorganic compounds. These characteristics make DMSO a widely used solvent in compound discovery laboratories for compound library storage. Normally DMSO ACS Spectrophotometric Grade is selected for library storage.
DMSO is also used in analytical or High Throughput Screening processes. The clean impurity profile of DMSO ACS Spectrophotometric Grade insures the DMSO will remain a consistent background that doesn’t contribute interferences.
Synthesis of API / Intermediates
Active Pharmaceutical Ingredients (API) are among the many organic compounds that may be synthesized with DMSO. The excellent solvent power of this dipolar aprotic solvent is responsible for its reputation as a ‘Super Solvent’.
When used as a reaction solvent, DMSO can improve selectivity and yield in many types of chemical reactions. The relatively high boiling point of DMSO allows higher temperatures than many solvents. DMSO is a useful polymer solvent, which has ramifications in pharmaceutical science.
As a reagent, DMSO is key to a class of mild and selectivity oxidation reactions (Swern, Pfitzner-Moffatt, Parihk-Doering, etc). DMSO can be used to form the dimsyl ion, which is a strong base useful in alkylation, nucleophilic displacement and condensation reactions. Many Active Pharmaceutical Ingredients (API) are initially synthesized in DMSO due these properties.
DMSO has various functions in the Biotechnology segment. DMSO is the most widely used medium for the cryopreservation of living cells and tissue. DMSO may be chosen during synthesis and purification of proteins or peptides. Similarly to its role in some small molecule pharmaceuticals, DMSO may be useful in drug delivery systems designed to deliver proteins, peptides or carbohydrates.
A unique combination of physical properties has established DMSO as the standard in cell preservation. When combined with 50% water, DMSO exhibits unique and interesting thermodynamic properties. This eutectic mixture of the combination remains a liquid at minus 80° C.
DMSO penetrates cell membranes and depresses the freezing point of contained water. As the temperature decreases in the cryopreservation cycle, the cell is protected from freezing and the deleterious effects of ice crystals.
DMSO is used in the cryopreservation of cells and biological tissue for a variety of end use applications. These include tissue banks, vaccines, drug delivery applications, cell culture and in laboratory cell testing.
Peptide Synthesis / Processing
DMSO is used as a reaction solvent in the solid phase synthesis of peptides, during coupling operations between resin-bound fragments and activated carboxyl groups on the incoming fragment. A variety of coupling agents have been reported in this step, including TBTU/HOBt/DIPEA, DIC/DHBt, and HBTU/ HOBt/DIPEA.
In a recent review of strategies for the convergent synthesis of proteins, it was reported that performing the coupling step in DMSO using a DCC/HOBt coupling system resulted in a low degree of product epimerization:
Adapted from Barlos, K.; Gatos, D. Biopolymers (Peptide Science), Vol. 51, 266-278 (1999)
Solubilizing Peptides and Proteins. DMSO is widely used to dissolve proteins / peptides for purification via preparative HPLC in reverse-phase mode. It is also used as a reaction solvent for protein modification reactions due to the ability to dissolve high molecular weight peptides when other solvents fail.
Histology and Cytology
Histological and cytological procedures are multi-stepped and time consuming. Dimethyl sulfoxide is added to proprietary blends of plastic polymer paraffin waxes. The DMSO reduces infiltration times and facilitates thin sectioning (Culling CFA. Handbook of Histopathological and Histochemical Techniques. 3rd ed. Sydney: Butterworths. 1974) DMSO is thought to scavenge residual transition solvent and probably alter tissue permeability by substituting for or removing bound water thus improving infiltration.
One example on the market is Paraplast Plus® that is similar to the original product except that Plus has added to it a low level (<0.1%) of dimethyl sulfoxide (DMSO) for faster tissue penetration. According to the manufacturer’s claims, this slight variation in composition typically results in a shortening of infiltration times by one third.
DMSO is also used in stains for nucleic acid where degree and intensity of staining is improved with the use of DMSO.