Ketoconazole Shampoo (DIY Recipe)

[OccamzRazer]

I've been compounding my own hair loss topicals for quite a few years now.

Even though I create complex formulations, ketoconazole is by far one of the most difficult compounds I've worked with. No wonder it's included in "Class II of the Biopharmaceutical Classification System".

It's extremely difficult to solubilise ketoconazole at a therapeutic concentration of 2% (or even 1%).

I'm trying to create a non-irritating, "gentle" alternative to the Nizoral shampoo. So I can use it daily.

And I simply can't find any skin-friendly, non-toxic solvents that solubilise ketoconazole at concentrations of 2% (or 1%).

I'm purposefully avoiding the sulfates used in Nizoral.

The only other Ketoconazole shampoo that doesn't use sulfates is Regenpure DR and they are barely able to get the ketoconazole concentration up to 1%.

The things that I've had slight success with are:

- Polysorbate 80
- Reducing the pH
- Ethanol (not suitable for a shampoo formulation)
- Propylene glycol (not suitable for a shampoo formulation)

Any thoughts, ideas, suggestions? All will be greatly appreciated!

Thank you

P.S. I've read virtually all the clinical literature on ketoconazole dissolution even the studies behind paywalls.

Regarding your initial question, I would just use ethanol, even if it isn't ideal for a shampoo formulation. Sorry I can't be of more help here.

 

[Archon]

I've been compounding my own hair loss topicals for quite a few years now.

Even though I create complex formulations, ketoconazole is by far one of the most difficult compounds I've worked with. No wonder it's included in "Class II of the Biopharmaceutical Classification System".

It's extremely difficult to solubilise ketoconazole at a therapeutic concentration of 2% (or even 1%).

I'm trying to create a non-irritating, "gentle" alternative to the Nizoral shampoo. So I can use it daily.

And I simply can't find any skin-friendly, non-toxic solvents that solubilise ketoconazole at concentrations of 2% (or 1%).

I'm purposefully avoiding the sulfates used in Nizoral.

The only other Ketoconazole shampoo that doesn't use sulfates is Regenpure DR and they are barely able to get the ketoconazole concentration up to 1%.

The things that I've had slight success with are:

- Polysorbate 80
- Reducing the pH
- Ethanol (not suitable for a shampoo formulation)
- Propylene glycol (not suitable for a shampoo formulation)

Any thoughts, ideas, suggestions? All will be greatly appreciated!

Thank you

P.S. I've read virtually all the clinical literature on ketoconazole dissolution even the studies behind paywalls.

Hey there, i would definitely gO with poly80, but beware it seems to feed fungus.
Could you go deeper on why you would avoid sulfates?

 

[Blue Water]

"Anything you put on your skin gets absorbed"

That's entirely and utterly false.

When it comes to transdermal absorption of a given compound, molecular weight and molecular geometry are the determining factors (but also chemical polarity, lipophilic/lipophobic properties and more).

Why do you think you don't drown every time you take a shower? Because water is repelled by the skin...

Why do you think we need vehicles and permeation enhancers to improve the transdermal absorption of compounds?

What you're saying speaks volumes about your understanding of pharmacodynamics and pharmacokinetics, or the lack thereof.

The molecular weight of ketoconazole is ~531 daltons which makes it very difficult to pass the stratum corneum.

However, some emerging hypotheses and anecdotes claim that the mid 500s in molecular weight might be the "gold zone" for topical medications which need to have a limited systemic absorption. Because the molecular weight is small enough to allow the compound to get to the derma papilla (in the case of KTZ) but large enough to prevent it from going further than that.

Even though this is a hypothesis, the clinical data clearly shows no systemic absorption.

Not to mention that the primary reason why oral ketoconazole is hepatoxic is because due to it being "oral" in nature doesn't allow it to skip 1st pass metabolism, whereas, topical does.

So in the highly unlikely event of a small percentage of the topical ketoconazole going systemic, it will be far less toxic.

But again, the average oral dose which is deemed toxic is 400 - 800mg of ketoconazole, and here we're talking about only 20mg of topically administered KTZ which is more than enough to induce a trichogenic effect.

I quoted the FDA because they have a summarised statement on the systemic side-effects of topical ketoconazole. I didn't want to inundate my already long post with additional quotes from independent studies.

And please don't tell me you're one of these people who "doesn't trust" the FDA.

If you don't trust the FDA, then you should disregard all of the chemotherapy drugs, heart medication, etc. that they've helped develop, which by the way, are saving lives as we speak.

The FDA has brought far more good than bad to the world of science, and this is non-negotiable. Only dilettantes and flat-earth proponents will say otherwise.

What about with penetration enhancers that are sometimes in these shampoos? Would the molecular weight of KTZ still prevent it from being absorbed, or would the penetration enhancers disrupt the skin barrier enabling it to go systemic? I'm less worried about the liver effect and more about the anti-androgen effect of systemic absorption.