Tolnaftate

TOLNAFTATE’S REMARKABLE TRANSFORMATION

Introduction to Tolnaftate

Tolnaftate, synthesized in the early 1960s by Japanese scientists, was classified as a Category 1 GRASE drug (Generally Recognized As Safe and Effective) by the U.S. FDA in 1965. The FDA issued the Final Monograph for tolnaftate on September 23, 1994, after confirming its safety with minimal adverse reactions like intense itching and skin irritation.

Solubility and Early Limitations

Initially, tolnaftate's insolubility in water and oil limited its effectiveness in suspensions, despite its broad in vitro activity against various fungi, including Epidermophyton, Microsporum, Trichophyton species, and Malassezia furfur. Tolnaftate inhibits squalene epoxidase, impacting fungal growth and biosynthesis.

Administration and Pharmacokinetics

Tolnaftate is ineffective when administered orally or parenterally, so it is only used topically. Studies show no systemic metabolism or percutaneous absorption. High doses in animals (14 g/kg orally in dogs) showed no toxicity, and topical application in rabbits did not cause sensitization or irritation. Human studies indicated negligible toxicity, even with extensive body application.

FDA Monograph and Regulations

The monograph system simplifies product manufacturing with tolnaftate, eliminating the need for pre-approval if guidelines are followed. The monograph details precise labeling requirements, including the mandatory statement: “This product is not effective on scalp or nails.” Deviating from approved formulations or combining tolnaftate with unapproved substances like colloidal silver or DMSO necessitates a New Drug Application (NDA).

Breakthrough with Soluble Tolnaftate

The Tetra Corporation revolutionized tolnaftate application by developing Soluble Tolnaftate, with particles less than 1 nm in size. This form is indefinitely stable in jojoba oil and penetrates skin and nails effectively, unlike suspensions that leave residue on the surface.

Solution vs. Colloid

Solution: Particles (0.1-1 nm) are not affected by gravity, ensuring stability and effective absorption without filtration.

Colloid: Particles are slightly affected by gravity and may separate over time. They are filterable if larger than 25 nm.

Solution = .1 to 1nm

In a Solution – Particles of Tolnaftate are not affected by gravity – Soluble Tolnaftate (solute) will not settle. (indefinitely stable) Tyndall Effect is the scattering of light by particles in a mixture. Solutions allow light to pass through. In a solution, the solute (tolnaftate) takes on the properties of the solvent (jojoba oil) = Soluble Tolnaftate.16 The smallest commercial filter available today is 25 nanometers. No filter available today can filter solutions. Solutions, therefore, are not filterable and by all standards, are the optimal delivery form for Active Pharmaceutical Ingredients.

Colloids = 1 to 1000nm

In Colloids – Particles are slightly affected by gravity. Brownian Motion (states that the random erratic movement of the solvent colliding with the solute particles keeps the solute from settling. They separate slowly on standing. (60 years (1 nanometer) to 2 days (1 Micron) – this is determined by particle size) Colloids are filterable if they are larger than 25 nanometers. Also, filterable by semi-permeable membranes found in the cell walls of all living organisms.

Suspension= >1000nm

In a Suspension – Particles are affected by gravity and will settle out in 30 minutes to 48 Hours. Tyndall Effect is the scattering of light by particles in a mixture. Suspensions DO NOT allow light to pass through. In a suspension, the solute DOES NOT take on the properties of the solvent. Suspensions are filterable. Also, filterable by semi-permeable membranes found in the cell walls of all living organisms.

Gold Standard in Tolnaftate Delivery

Soluble Tolnaftate is the industry standard for effective delivery to infection sites. The Tetra Corporation, leading in tolnaftate technology since 1989, maintains exclusive, proprietary processes. Their products, including Formula 7® and FungiFoam®, ensure optimal penetration and efficacy.