Transdermal pentoxifylline cream/gel

[hope4thebest]

Hello everyone,

So I haven't been on the forum for many reasons, but I'm back and I got an idea about transdermal pentoxi. Turns out it has already been suggested as part of DMSO+X so I didn't come up with anything groundbreaking. However, I think the formulation could be improved to help with absorption and delivery, because I don't see no reason why it shouldn't work.

Looking at the studies from Dr. Paulis, it's pretty clear that pentoxi makes the biggest difference in treating Peyronie's, but he only does injections once every two weeks, I believe. Now imagine what could happen if we could come up with a good formulation that absorbs well and can be applied MULTIPLE times a day?? This could really be a significant breakthrough.

The problem is that the pharmacology of dermatological preparations isn't an easy science. I wonder if we have any dermatologists or pharmacists here, that could be helpful.

Now... from what I was able to find out so far, pentoxifylline is a hydrophilic molecule with a moderate water solubility, 43-77 mg/ml (depending on the source), and according to some websites, pretty poor solubility in DMSO, about 10 mg/ml.

The problem with hydrophilic molecules is that they aren't super good at permeating the skin as far as I understand because skin is made of lipids and it may be helped by making an emulsion, which seems to be a little complicated and I haven't done enough research on it yet. It also could be combined with a lipid base, like Lipoderm, which some US pharmacies seem to use with pentoxi.

There already are multiple commercial creams with pentoxifylline, but most of them seem to have other unnecessary ingredients and are prescription, so could be harder to obtain and personally, I don't want unnecessary crap on my penis.

So things that could be combined with pentoxifylline:

DMSO - permeation enhancer/solvent, but in this case water is better solvent
Transcutol - permeation enhancer/solvent, solubility of pentoxi unclear
Labrasol - permeation enhancer/ solvent, solubility unclear, has lipids/caprylic, different than Transcutol

The obvious choice and most simple choice would probably be either DMSO in low concentration, perhaps 50/50 with water to allow sufficient solubility of pentoxi, or Transcutol. The advantage to Transcutol is that it's not toxic and not irritating, but isn't as strong as DMSO and the solubility is unclear, however shouldn't be worse than DMSO, in my opinion.

The slight issue with DMSO is that one recent study shows that it might be slightly toxic at higher concentrations, but should be safe at about 2 ml per day (human equivalent dose from mice study), which may be sufficient for us:
https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.2146
However, I'm sure that some people on this forum and countless people in other places have used it in higher doses for prolonged time without any issues, so take it with a grain of salt....

From Chat GPT:

For a transdermal formulation of pentoxifylline, Tween 80 and Labrasol can serve as surfactants and solubilizers, assisting in the formation of stable formulations. However, if you want to achieve a gel-like consistency or control the release of the drug over time, incorporating a gelling agent might be beneficial.

Common gelling agents used in topical formulations include:

Carbomers
Hydroxypropyl methylcellulose (HPMC)
Poloxamers
Xanthan gum
The choice of the gelling agent would depend on the specific characteristics you aim to achieve in terms of viscosity, spreadability, and release profile. Experimentation and testing are crucial to finding the right combination of components for your specific transdermal formulation objectives.

So just like the youtuber MrEcz did, xantham gum, or other things could be added.

For a transdermal formulation of pentoxifylline, you could consider the following components:

Carriers:

Isopropyl myristate
Propylene glycol
Ethanol
Polyethylene glycol (PEG)
Dimethyl sulfoxide (DMSO)
Solubility Enhancers:

Transcutol (diethylene glycol monoethyl ether)
Oleic acid
Labrasol
Cremophor EL
Lauroglycol FCC
Surfactants:

Tween series (e.g., Tween 80)
Span series (e.g., Span 80)
Sodium lauryl sulfate
Brij series (e.g., Brij 30)
Pluronic series (e.g., Pluronic F127)
These components can be combined to form microemulsions or other suitable formulations. The selection and optimization of these ingredients should be based on their compatibility with pentoxifylline, their ability to enhance solubility and permeation, and considerations for skin safety.

It's important to note that the specific formulation would require experimental testing and optimization. Conducting permeation studies, compatibility tests, and assessing the physical and chemical stability of the formulation will help determine the most effective combination for transdermal delivery of pentoxifylline.

Optimizing a transdermal formulation for complete skin permeation of pentoxifylline requires careful consideration of various factors. While it's challenging to pinpoint a single "best" combination without specific formulation experiments, a potential formulation may include:

1. **Solvent/Carrier:**
   - A combination of DMSO (Dimethyl sulfoxide) and Transcutol (diethylene glycol monoethyl ether) for their solubilizing and penetration-enhancing properties.

2. **Surfactant:**
   - A suitable surfactant like Tween 80, which can contribute to the formation of a stable formulation and aid in solubilization.

3. **Lipid Component:**
   - Incorporate a lipophilic component like isopropyl myristate or Labrasol to enhance the lipophilicity of the formulation and promote penetration.

4. **Optimizing Ratios:**
   - The specific ratios of these components should be optimized through experimentation to achieve the best results for pentoxifylline.

It's essential to conduct permeation studies, compatibility assessments, and skin irritation tests during the formulation development process. Additionally, considering the safety and regulatory aspects of the selected components is crucial for the development of a transdermal formulation. Keep in mind that the effectiveness of the formulation may also depend on the specific characteristics of the skin area where the transdermal delivery is intended.

The issue is that I'm chronically ill myself, and I can't do very much myself, so it would be great if anyone could jump in with ideas.
 

[Realvinni2000]

It would be great.