Working with Methylene Blue: Best Practices for Compounding and Cleanup

Thu, 15 Feb 2024 00:56:45 GMT

by Stacey Lemus, BS, PCCA Senior Formulation Specialist and Project Manager

Pro Tips for Compounding Methylene Blue

Preparation and focus is key to achieving positive results. Prior to compounding with methylene blue, line your hood work surface with spill mats or low-lint disposable towels to contain any spills. Work slowly and diligently.

Your containment ventilated enclosure (CVE), when certified, has a specific airflow range to meet best practice standards. If you notice excess pull of weighing paper or powders toward the back of the hood while compounding, consider having your CVE certification company check the airflow parameters. It may also be helpful to adjust the airflow to the lower end of the range of the best practices standard. This may drastically reduce the amount of powder residue that can stain your CVE and balance.

When mixing topical formulations using an electronic mortar and pestle (EMP), single-use disposable mixing blades are a great option. PCCA carries a variety of sizes to accommodate different EMP jar sizes (PCCA #35-2449, #35-2450, #35-2451). These are compatible with detachable shafts (PCCA #35-2452). The single-use blades are twisted on to the end of the shaft and are easy to remove after mixing for disposal.

Methylene blue powder requires pulverizing to make powder capsules, oil-based capsules or oil suspensions. We advise using a glass mortar and pestle. Other mortars, such as ceramic or plastic, are made of more porous materials that are prone to staining.

Pro Techniques for Cleaning After Compounding Methylene Blue

We suggest rinsing all equipment and devices immediately after use with isopropyl alcohol and cleaning it with an EPA-registered cleaning agent that is suitable for the equipment.

We also suggest following these clean-up tips after compounding powder capsules:

After properly rinsing all equipment and devices, prepare a clean surface inside the hood.
Set up a designated plastic tub in the hood containing enough isopropyl alcohol 70% to cover the plates.
Carefully submerge the capsule machine plates into the plastic basin.
Stage the bin and contents outside of the hood using proper technique.
Allow three (3) minutes of soaking.
Pour out the rinsing alcohol into an appropriate container for disposal and refill with fresh alcohol (barely cover).
Move the container gently from side to side, while on the counter, to facilitate removal of the staining inside the holes.
If necessary, repeat steps 6 and 7, allowing three (3) minutes of soaking in between.

Remember, powder capsules are not the only methylene blue formulation. Get innovative! Explore alternate formulations, such as oil capsules, to avoid tricky dosage forms. Powder capsules can be messy to compound, and compounding oil-filled capsules is a great way to avoid excess cleanup.

We’re here to assist you!

PCCA members may access PCCA Play training videos on techniques for compounding oil capsules. Members with clinical services may contact our Clinical Services team for help when compounding methylene blue and for other compounding questions.

Access the free webinar, Navigating the Lab with Methylene Blue — Compounding Techniques and Best Practices, on PCCA Play.

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

Methylene Blue: Something Old and Something Blue

Wed, 26 Apr 2023 11:00:00 GMT

Updated: 07/06/2023

by Don Bottoni, RPh, PCCA Clinical Compounding Pharmacist

Methylene blue is an aniline dye that was synthesized for the textile industry in 1876 by Heinrich Caro, an employee of the chemical firm, BASF. It is a blue dye that was developed for staining cotton. Scientists began using dyes to stain microbes for more detailed study under the microscope. In 1885, Paul Ehrlich published an article on staining tuberculosis bacillus with methylene blue. He developed a theory that if the methylene blue could stain the organism and not the surrounding tissue, methylene blue would have detrimental effects on that organism. Essentially, he was proving that the structure of a chemical determines the biological effects of that chemical.

Methylene blue was used to treat various diseases to eliminate pathogens without damaging the tissue. During World War II, methylene blue was used on soldiers to treat malaria. It was the first synthetic medicine used to treat illnesses in human patients. Methylene blue is still considered for use in malaria patients and is experiencing a revival of interest.

Blue Oxidized State
Methylene blue is a unique derivative of phenothiazines. In its oxidized state, it is blue and is an electron donor. In its colorless state (leucomethylene blue), it is in a reduced state and will accept electrons. These two molecules comprise an “autoxidizing redox” system, which is a reversible oxidation-reduction system. This complex allows methylene blue to support the mitochondrial electron chain inside our cells, which supports respiration inside our cells. It is this ability to transport electrons, and thus oxygen inside our cells, which allows it to be used as a treatment for methemoglobinemia, cyanide poisoning and carbon dioxide poisoning. Methylene blue can serve as an oxygen transport system while our hemoglobin is not functioning properly.

Neurological Conditions
There are many neurological conditions where methylene blue has been studied. Those conditions include Alzheimer’s disease, autism, depression, neurodegenerative diseases, Parkinson’s disease and traumatic brain injury.

In many of these conditions, researchers consider the increase of oxygenation in the cells as the supporting mechanism of action of methylene blue. The increase in oxygenation increases cellular oxygen levels and respiration, increases glucose uptake and increases production of ATP — the energy containing substance in our cells. Methylene blue also decreases the oxidative stress caused by reactive oxygen species (ROS) and protects the nerves from damage. Methylene blue can inactivate these ROS. Also, by increasing ATP activity, methylene blue can increase metabolic energy, increase DNA repair and decrease neurodegeneration.

Methylene blue has also been shown to affect the levels of various neurotransmitters in our nervous system. Methylene blue is an MAO inhibitor, helping to increase levels of serotonin, norepinephrine and can increase acetylcholine levels in the cells.

Treating Patients
A majority of patients can be maintained at a daily dose of 15 mg in capsule form. A dose of 50 mg taken twice daily has been used to treat Lyme disease. A starting dose of 200 mg has been used in patients with COVID. This dose should be started as soon as possible; higher doses have been used.

There was an interesting French study of 2,500 cancer patient who were treated with a regimen that included methylene blue. At the end of the study, none of the 2,500 patients developed an influenza-like illness, including COVID.

Methylene blue is best taken in the morning because it can be a mild stimulant and disrupt sleep patterns.

Clinical considerations include not using methylene blue in patients on MAO inhibitors, or patients taking SSRIs or SNRIs. Methylene blue should not be taken with dapsone and is contraindicated in patients with renal disease or patients with hypersensitivity to methylene blue. It is also contraindicated during pregnancy.

References

Sloan, M. (2021). The Ultimate Guide to Methylene Blue. Accessed March 2023 at endalldisease.com

Tucker, D., Lu, Y., & Zhang, Q. (2018). From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue. Mol Neurobio, 55(6), 5137–5153. Accessed March 2023 at https://doi.org/10.1007/s12035-017-0712-2

Rojas, J. C., Bruchey, A. K., & Gonzalez-Lima, F. (2012). Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobio, 96(1), 32–45. Accessed March 2023 at https://doi.org/10.1016/j.pneurobio.2011.10.007

Kayabasi, Y., Erbas, O. (2020) Methylene blue and its importance in medicine. D.J. Med Sci 2020;6(3):136-145. Accessed April 2023 at https://www.journalmeddbu.com/full-text-pdf/213

Schirmer, R. H., Coulibaly, B., Stich, A., et al. (2003). Methylene blue as an antimalarial agent. Redox report : communications in free radical research, 8(5), 272–275. Accessed April 2023 at https://doi.org/10.1179/135100003225002899

Gonzalez-Lima, F., & Auchter, A. (2015). Protection against neurodegeneration with low-dose methylene blue and near-infrared light. Front Cell Neurosci, 9, 179. Accessed April 2023 at https://doi.org/10.3389/fncel.2015.00179

Atamna, H., Nguyen, A., Schultz, C., et al. (2008). Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB J. 22(3):703-712. Accessed April 2023 at https://doi.org/10.1096/fj.07-9610com

Biju, K. C., Evans, R. C., Shrestha, K., et al. (2018). Methylene Blue Ameliorates Olfactory Dysfunction and Motor Deficits in a Chronic MPTP/Probenecid Mouse Model of Parkinson's Disease. Neuroscience. 2018;380:111-122. Accessed April 2023 at https://doi.org/10.1016/j.neuroscience.2018.04.008

THE PCCA BLOG

Working with Methylene Blue: Best Practices for Compounding and Cleanup

Pro Tips for Compounding Methylene Blue

Pro Techniques for Cleaning After Compounding Methylene Blue

We’re here to assist you!

Methylene Blue: Something Old and Something Blue