SLU-PP-332 Solution Discussion

@Trenbolonetax you’ll probably want to take a look at this bro.


It’s why I add some urea to the mix.
 
@Trenbolonetax you’ll probably want to take a look at this bro.


It’s why I add some urea to the mix.
Thank you!
 
@Trenbolonetax the discussion about SLU-PP-332 in another thread got me thinking more about how to go intramuscular instead of oral to better match the bioavailability of the intraperitoneal injections used in the mice studies.

The lab mice were probably injected with a DMSO solution which would likely be intolerable for humans as I understand it. Bear in mind that my understanding is likely both limited and flawed, so consider this to be completely hypothetical and probably little more than mental masturbation. That said, I've got an idea on how to make an MCT-based emulsion that should achieve around 200 mg/ml concentration and be tolerable for intramuscular administration, if you're interested.
 
@Trenbolonetax the discussion about SLU-PP-332 in another thread got me thinking more about how to go intramuscular instead of oral to better match the bioavailability of the intraperitoneal injections used in the mice studies.

The lab mice were probably injected with a DMSO solution which would likely be intolerable for humans as I understand it. Bear in mind that my understanding is likely both limited and flawed, so consider this to be completely hypothetical and probably little more than mental masturbation. That said, I've got an idea on how to make an MCT-based emulsion that should achieve around 200 mg/ml concentration and be tolerable for intramuscular administration, if you're interested.
You have piqued my curiosity…
 
@Trenbolonetax the discussion about SLU-PP-332 in another thread got me thinking more about how to go intramuscular instead of oral to better match the bioavailability of the intraperitoneal injections used in the mice studies.

The lab mice were probably injected with a DMSO solution which would likely be intolerable for humans as I understand it. Bear in mind that my understanding is likely both limited and flawed, so consider this to be completely hypothetical and probably little more than mental masturbation. That said, I've got an idea on how to make an MCT-based emulsion that should achieve around 200 mg/ml concentration and be tolerable for intramuscular administration, if you're interested.

I’m also intrigued.
 
You have piqued my curiosity…
To prepare a potential emulsion formulation of SLU-PP-332 at a concentration of 200 mg/mL for injection, I would consider both its hydrophilic and lipophilic properties. By examining its chemical structure, I found that SLU-PP-332 has nonpolar, lipophilic parts, like aromatic rings, which dissolve well in oils, along with polar, hydrophilic groups, such as hydroxyl or amine groups, that interact well with water. This combination suggests that an emulsion-based approach, allowing SLU-PP-332 to interact with both oil and water phases, might be effective.

To create this emulsion, MCT oil could serve as the main carrier, as it is commonly used in injectable formulations for its biocompatibility and ability to dissolve lipophilic compounds. Since achieving a high concentration might require extra solubility support, adding a small amount of ethanol as a co-solvent could help ensure that SLU-PP-332 fully dissolves in the oil phase.

To stabilize the emulsion and prevent separation, lecithin and polysorbate 80 (Tween 80) could act as emulsifiers. These emulsifiers, with both hydrophilic and lipophilic ends, would sit at the boundary between the oil and water, reducing surface tension and promoting the formation of small, stable droplets. This would ideally keep the emulsion homogeneous, which is essential for consistent dosing and safety in injection.

For the aqueous component, phosphate-buffered saline (PBS) might be preferable over saline, as it provides a stable, physiological pH around 7.4, likely improving compatibility with human tissues. This buffering could help keep the emulsion’s pH close to that of the body, reducing potential irritation.

The hypothetical preparation process would start with dissolving SLU-PP-332 in MCT oil with ethanol, followed by adding the emulsifiers to the mixture. I would then introduce the PBS phase gradually with stirring, using high-shear mixing or sonication to achieve small, uniform droplets (ideally under 5 microns), which would help prevent tissue irritation upon injection. To ensure sterility, the emulsion should be filtered through a 0.22 µm filter if possible and stored in amber vials at 4°C to maintain stability.

Testing requirements would include confirming the emulsion’s stability, concentration, particle size, and sterility. Techniques like HPLC for concentration and dynamic light scattering for particle size would help ensure that the formulation is safe, effective, and suitable for injection. Throughout the process, prioritizing factors such as pH stability and physiological compatibility makes PBS likely the better choice for the aqueous component, given its buffering advantage over saline.

Disclaimer: I used ChatGPT interactively to analyze SLU-PP-332's chemical structure at PubChem (Slu-PP-332) as a starting point since. From there, I queried ChatGPT about intraperitoneal administration to mice where I found that DMSO is commonly used in animal testing, but that it would be problematic for human applications. That led me to organic solvents like oils with MCT being my personal preference as a starting point. From there, I queried about intramuscular administration in humans and various concentrations from 100 mg/ml to 200 mg/ml. At lower concentrations the ethanol might not be necessary, but at the higher concentrations is almost certainly would be. From there it was just questions about how to refine the emulsifying process to meet my concentration and safety goals.

And yes, I do have a specific recipe that ChatGPT presented me with, but I still want to go over the numbers more first. You could probably copy-paste what I wrote into ChatGPT, Google Gemini or the like and ask for specific processes if you want but be careful and always double-check what comes out of the AI process.
 
To prepare a potential emulsion formulation of SLU-PP-332 at a concentration of 200 mg/mL for injection, I would consider both its hydrophilic and lipophilic properties. By examining its chemical structure, I found that SLU-PP-332 has nonpolar, lipophilic parts, like aromatic rings, which dissolve well in oils, along with polar, hydrophilic groups, such as hydroxyl or amine groups, that interact well with water. This combination suggests that an emulsion-based approach, allowing SLU-PP-332 to interact with both oil and water phases, might be effective.

To create this emulsion, MCT oil could serve as the main carrier, as it is commonly used in injectable formulations for its biocompatibility and ability to dissolve lipophilic compounds. Since achieving a high concentration might require extra solubility support, adding a small amount of ethanol as a co-solvent could help ensure that SLU-PP-332 fully dissolves in the oil phase.

To stabilize the emulsion and prevent separation, lecithin and polysorbate 80 (Tween 80) could act as emulsifiers. These emulsifiers, with both hydrophilic and lipophilic ends, would sit at the boundary between the oil and water, reducing surface tension and promoting the formation of small, stable droplets. This would ideally keep the emulsion homogeneous, which is essential for consistent dosing and safety in injection.

For the aqueous component, phosphate-buffered saline (PBS) might be preferable over saline, as it provides a stable, physiological pH around 7.4, likely improving compatibility with human tissues. This buffering could help keep the emulsion’s pH close to that of the body, reducing potential irritation.

The hypothetical preparation process would start with dissolving SLU-PP-332 in MCT oil with ethanol, followed by adding the emulsifiers to the mixture. I would then introduce the PBS phase gradually with stirring, using high-shear mixing or sonication to achieve small, uniform droplets (ideally under 5 microns), which would help prevent tissue irritation upon injection. To ensure sterility, the emulsion should be filtered through a 0.22 µm filter if possible and stored in amber vials at 4°C to maintain stability.

Testing requirements would include confirming the emulsion’s stability, concentration, particle size, and sterility. Techniques like HPLC for concentration and dynamic light scattering for particle size would help ensure that the formulation is safe, effective, and suitable for injection. Throughout the process, prioritizing factors such as pH stability and physiological compatibility makes PBS likely the better choice for the aqueous component, given its buffering advantage over saline.

Disclaimer: I used ChatGPT interactively to analyze SLU-PP-332's chemical structure at PubChem (Slu-PP-332) as a starting point since. From there, I queried ChatGPT about intraperitoneal administration to mice where I found that DMSO is commonly used in animal testing, but that it would be problematic for human applications. That led me to organic solvents like oils with MCT being my personal preference as a starting point. From there, I queried about intramuscular administration in humans and various concentrations from 100 mg/ml to 200 mg/ml. At lower concentrations the ethanol might not be necessary, but at the higher concentrations is almost certainly would be. From there it was just questions about how to refine the emulsifying process to meet my concentration and safety goals.

And yes, I do have a specific recipe that ChatGPT presented me with, but I still want to go over the numbers more first. You could probably copy-paste what I wrote into ChatGPT, Google Gemini or the like and ask for specific processes if you want but be careful and always double-check what comes out of the AI process.
This is interesting, but I'm not sure it's practical for the average homebrewer. I don't know if many people will have a high-shear mixer or ultrasonic homogenizer, let alone a dynamic light scattering particle analyzer.
 
This is interesting, but I'm not sure it's practical for the average homebrewer. I don't know if many people will have a high-shear mixer or ultrasonic homogenizer, let alone a dynamic light scattering particle analyzer.
The HPLC analysis would probably best go through a facility like Janoshik's, of course.

The price of a high-shear emulsifier mixer though might not be that far of a stretch for many homebrewers.
 
I've been messing around with 332 for the past few days. I first tried DMSO: PEG 400:Tween 80:ddH2O at 5:40:5:50 ml, mixing with a mag mixer, but upon my introducing the H2O, the 332 dropped out of solution.

Next I tried the same as above, but substituted EO for the ddH2O. This held. Filtered using two 22um syringe filters into a 100ml sterile vial. Still in solution 3 days later stored at room temp.

Both solutions were for 500mg of 332, so 100mg/ml in the DMSO, and 5mg/ml of the final solution.

I started by injecting 1mg bid, and didn't have any problems, so moved to 2.5mg, still no probs. I think I'll do a month at 2.5mg bid, and see what I can see. With the EO it's thin enough to use 31g slin pins.

I don't trust this to be orally available at all so am not looking at suspensions at all. I have thought about making a nasal spray, would likely swap out some or all of the EO for EtOH for that.

Traveling for work the first half of this week, but will start another thread to document my month of 5mg/day use when I'm back...
 
I've been messing around with 332 for the past few days. I first tried DMSO: PEG 400:Tween 80:ddH2O at 5:40:5:50 ml, mixing with a mag mixer, but upon my introducing the H2O, the 332 dropped out of solution.

Next I tried the same as above, but substituted EO for the ddH2O. This held. Filtered using two 22um syringe filters into a 100ml sterile vial. Still in solution 3 days later stored at room temp.

Both solutions were for 500mg of 332, so 100mg/ml in the DMSO, and 5mg/ml of the final solution.

I started by injecting 1mg bid, and didn't have any problems, so moved to 2.5mg, still no probs. I think I'll do a month at 2.5mg bid, and see what I can see. With the EO it's thin enough to use 31g slin pins.

I don't trust this to be orally available at all so am not looking at suspensions at all. I have thought about making a nasal spray, would likely swap out some or all of the EO for EtOH for that.

Traveling for work the first half of this week, but will start another thread to document my month of 5mg/day use when I'm back...
Looking forward to the log!
 
Have you tried only mct or a solution of mct and dmso? It’s hydrophobic so it should hold fine
I haven't, but agree that it should be fine, particularly 5:95 DMSO:MCT. But I did EO because I was worried about viscosity with the MCT. Unlike AAS, I wouldn't want to add heat to this.

Maybe I can get a hold of some of Diddy's now extra baby oil?
 
Alright, y'all have officially got my interest. What do you think the max concentration is in something like 5:95 DMSO:MCT?
Don't know and won't know until we try, I think. Looking at different mainline suppliers' data sheets, I've seen between 50mg/ml to 125mg/ml in DMSO, 2mg/ml in EtOH, and no solubility in water.

Now that I've got 100ml of 5mg/ml, I'm likely done messing with the injectable for a bit. I'm going to send some of it and the raw off to Jano for testing.

If I get around to it soon, I'll also send off whatever intranasal I make.
 
I've been messing around with 332 for the past few days. I first tried DMSO: PEG 400:Tween 80:ddH2O at 5:40:5:50 ml, mixing with a mag mixer, but upon my introducing the H2O, the 332 dropped out of solution.

Next I tried the same as above, but substituted EO for the ddH2O. This held. Filtered using two 22um syringe filters into a 100ml sterile vial. Still in solution 3 days later stored at room temp.

Both solutions were for 500mg of 332, so 100mg/ml in the DMSO, and 5mg/ml of the final solution.

I started by injecting 1mg bid, and didn't have any problems, so moved to 2.5mg, still no probs. I think I'll do a month at 2.5mg bid, and see what I can see. With the EO it's thin enough to use 31g slin pins.

I don't trust this to be orally available at all so am not looking at suspensions at all. I have thought about making a nasal spray, would likely swap out some or all of the EO for EtOH for that.

Traveling for work the first half of this week, but will start another thread to document my month of 5mg/day use when I'm back...
I have zero direct experience with EO and only have limited experience with DMSO. Gotta get that out of the way first.

I ran some hypotheticals based on DMSO + MCT and EO + MCT with target concentration of 200 mg/ml of SLU-PP-332 and a goal of an intramuscular injectable which is tolerable to humans.

Projection for DMSO + MCT: 150-200 mg/ml concentration feasible at 5-10% DMSO.
Projection for EO + MCT: 200-300 mg/ml concentration easily achievable ay 30-40% EO with 250 mg/ml being realistic and stable.

Both of these should be doable with magnetic mixing alone, but limited low-heat exposure (37-40 C) shouldn't negatively affect the solution. The EO + MCT would be the better of the two choices.

I also checked for other cosolvents that might meet this use case and got benzyl benzoate and glycerol formal as options for higher concentration intramuscular injectables.

I'm curious as to your thoughts on these options.
 
I have zero direct experience with EO and only have limited experience with DMSO. Gotta get that out of the way first.

I ran some hypotheticals based on DMSO + MCT and EO + MCT with target concentration of 200 mg/ml of SLU-PP-332 and a goal of an intramuscular injectable which is tolerable to humans.

Projection for DMSO + MCT: 150-200 mg/ml concentration feasible at 5-10% DMSO.
Projection for EO + MCT: 200-300 mg/ml concentration easily achievable ay 30-40% EO with 250 mg/ml being realistic and stable.

Both of these should be doable with magnetic mixing alone, but limited low-heat exposure (37-40 C) shouldn't negatively affect the solution. The EO + MCT would be the better of the two choices.

I also checked for other cosolvents that might meet this use case and got benzyl benzoate and glycerol formal as options for higher concentration intramuscular injectables.

I'm curious as to your thoughts on these options.
Benzyl Benzoate is something that is in basically all current oil injectables, so that one seems like a phenomenal option, unless I am missing something?
 
Back
Top