Use of Polymers, minimalist ingredients.

DeepTitanDeepTitan Member
edited August 6 in Innovation
Hi, I don't understand concepts well enough, so appreciate if you can correct my understandings below, appreciate it.

a) I read somewhere that you use for transdermal drug delivery, cationic polymers (i.e. positive charge polymers) as skin and hair are negatively charged, so these polymers bind to the skin, and in that process, the product gets a chance to permeate through the skin barrier.

b) so while the above is merely one component (i.e. binding to skin) of topical delivery science, another would be to force the product to actually enter the skin.  I can see 2 methods: 1. diffusion, 2. transport.  What factors help diffusion and transport?  

c) Diffusion: I can think of pH of product solution as helping with diffusion?.  Transport:  As for transport, maybe mixing an ingredient that has a skin transporter present?  What would be transporter ingredient?

d) so what happens if you combine cationic polymers (such as chitosan, guar gum) with anionic (such as xanthan gum).  You end up with a Polyelectrolyte Complex.  1. Would that be not suitable for Transdermal use?  2. Would the application be for oral delivery instead?

e) Can you comment on this topical formulation with least ingredients but still sufficient to penetrate at least in epidermal, but preferably in dermis as well: 

Active ingredients (safe even if goes into systemic circulation): x (hard to dissolve, lipophilic product), y (hydrophilic product)

Solvents: 1. try to dissolve in healthiest oils first.  2 If fail, Glycerin, 3. If fail Propylene glycol

Polymers: For max skin absorption: what do you think about: Gum arabic vs Guar gum vs Chitosan vs Xanthan gum vs Sodium Hyaluronate.   How would each fare for dermal vs epidermal absorption? 

Short-term stability/preservation: citric acid, edta

f) Is there something lacking in above.  How do you think about adding sunflower lecithin to the above?

Thanks a lot, sorry for this being long. 

Comments

  • is there way to edit original thread? 
    Headline is too cheesy should be:  Use of Polymers, minimalist ingredients.
    e1: should have read: try to dissolve in healthiest oil (for lipophilic) and water (for hydrophilic) components. 
    e3: If fail, Propylene Glycol or Alcohol (e.g. Everclear 190)
  • PharmaPharma Member, Pharmacist
    DeepTitan said:
    Hi, I don't understand concepts well enough (obviously... no offense!), so appreciate if you can correct my understandings below, appreciate it.

    a) I read somewhere that you use for transdermal drug delivery, cationic polymers (i.e. positive charge polymers) as skin and hair are negatively charged, so these polymers bind to the skin, and in that process, the product gets a chance to permeate through the skin barrier. Are you sure you don't confuse it with transfection? Polymers on dead matter usually don't work (with some exceptions but applications therewith are highly limited).

    b) so while the above is merely one component (i.e. binding to skin Precisely, it binds to skin and then sticks there) of topical delivery science, another would be to force the product to actually enter the skin (that's one of the standard ways to do it, it's called occlusion and works by the principle of solubility/insolubility).  I can see 2 methods: 1. diffusion (that would be the another standard which it the one probably most often referred to in cosmetics when talking about penetration enhancers), 2. transport (in cosmetics, one can rarely use a transport system for an active ingredient mostly because it involves covalent binding and living cells which are only reached after the hard part has been achieved i.e. penetration through epidermis).  What factors help diffusion and transport? Laws of physics and principles of biology :)

    c) Diffusion: I can think of pH of product solution as helping with diffusion? Anything which creates a gradient such as pH may be used for some things under certain circumstances. However, pH is mostly used to tune lipophilicity/hydrophilicity of acidic and alkaline actives.  Transport:  As for transport, maybe mixing an ingredient that has a skin transporter present? (??? You mean like gene technology?)  What would be transporter ingredient? Again, ???

    d) so what happens if you combine cationic polymers (such as chitosan, guar gum) with anionic (such as xanthan gum).  You end up with a Polyelectrolyte Complex.  1. Would that be not suitable for Transdermal use? Likely not. What's the point of that most likely precipitated blend anyway? 2. Would the application be for oral delivery instead? Why?

    e) Can you comment on this topical formulation with least ingredients but still sufficient to penetrate at least in epidermal, but preferably in dermis as well: 

    Active ingredients (safe even if goes into systemic circulation): x (hard to dissolve, lipophilic product), y (hydrophilic product) If you use both, the vehicles for the two will have to be different, unless you use some injection device such as CLICK.

    Solvents: 1. try to dissolve in healthiest oils first (Define healthy. Why an oil?).  2 If fail, Glycerin, 3. If fail Propylene glycol If it fails with glycerin, why should it work with propylene glycol?

    Polymers: For max skin absorption: what do you think about: Gum arabic (it's used for oral drug delivery of lipophilic actives) vs Guar gum vs Chitosan vs Xanthan gum vs Sodium Hyaluronate.   How would each fare for dermal vs epidermal absorption? Absorption of what? An active or the polymer itself? Low molecular weight hyaluronic acid does penetrate to a degree, against all predictions and principles of skin penetration, though I'm not aware that this would help penetration of other ingredients in any regard. Same goes for a very few other polymers such as heparan. Chitisan, if properly formulated, may work, the others are just polymeric thickeners and gel builders.

    Short-term stability/preservation: citric acid, edta That's not preservation, that's chelation. Also, they are partially incompatible with chitosan and do not really contribute to physical stability.

    f) Is there something lacking in above. Yes, there is: some books on your shelf and a sound basic knowledge. Again, no offense.  How do you think about adding sunflower lecithin to the above? I think that reading those books first... or maybe just buy active ingredients encapsulated in lecithin based liposomes or the like might be easier.

    Thanks a lot, sorry for this being long.
    See comments in italic.
  • First “thanks” A LOT for sharing your knowledge, this meant a lot.  I had to do plenty of homework to catch up on my knowledge before I could post this:

     

    1.  Earlier you wrote:  transport (in cosmetics, one can rarely use a transport system for an active ingredient mostly because it involves covalent binding and living cells which are only reached after the hard part has been achieved i.e. penetration through epidermis).

     

    I use an equipment - microneedling device.  You correctly pointed out that substance would just sit on the dead cells of skin.  I was thinking that using positively charged cationic polymer, immediately after (i.e. before the punctured hole closes), would with some reasonable efficiency diffuse or bind to skin cells?

     

    2. Earlier:  Transport:  As for transport, maybe mixing an ingredient that has a skin transporter present? (??? You mean like gene technology?)  What would be transporter ingredient? Again, ???

     

    Yes, off course while the use is not for that, the use is merely to get the sterile beneficial ingredient get into atleast the epidermis (and in some cases the dermis as well).  What ingredient, that I am not sure, what can be added for that purpose, but I was thinking e.g. mixing in Vitamin D3, for which cells have transporters, but I don’t know if at least theoretically that should help or not.

    Earlier:  so what happens if you combine cationic polymers (such as chitosan, guar gum) with anionic (such as xanthan gum).  You end up with a Polyelectrolyte Complex.  1. Would that be not suitable for Transdermal use? Likely not. What's the point of that most likely precipitated blend anyway? 2. Would the application be for oral delivery instead? Why?

     

    I feel that people make so many products without thinking the basic science, and that is why you get sub-optimal benefit (if any) from using the product.  I feel this is an important concept that many miss, but one that bothers me.  I am a stickler for accuracy (saying it not as a boast, sadly its my disease, I don’t like to make mistakes).  So I keep wondering, what the basic science is (or can be inferred on it).  So while I understand cationic polymer use, I don’t understand anionic polymer use (I see it in oral formulations), and I don’t follow the Polyelectrolyte complex use (apart from shielding from the stomach acids).

    Earlier: Can you comment on this topical formulation with least ingredients but still sufficient to penetrate at least in epidermal, but preferably in dermis as well: 

    Active ingredients (safe even if goes into systemic circulation): x (hard to dissolve, lipophilic product), y (hydrophilic product) If you use both, the vehicles for the two will have to be different, unless you use some injection device such as CLICK.

     

    Why do you say the vehicle has to be different?  I typically use: smallest quantity of Sunflower Lecithin as that combines both (lipophilic, hydrophilic).  I think alcohol, glycerin, propylene glycol acts similarly but less efficiently (as they cannot encapsulate).

     

    That paper is very nice, though I do struggle with finding such devices as they do not build them specifically for the topical penetration, except micro-needling devices.  E.g. electrophoresis – electric current devices.  How does a substance penetrate inside skin.  a) device challenge:  most have 2 electrodes.  I don’t see the point of putting 2 electrodes on skin as that would not do anything, except moving things between the 2 electrodes.  I mean, my purpose is to move the substance “into” the skin and not between the 2 electrodes.  b) formulation challenge:  So the cell surface is negatively charged, which means your topical formulation should have positive charge? But then how do pos and neg electrodes come into play?


    Solvents: 1. try to dissolve in healthiest oils first (Define healthy. Why an oil?).  2 If fail, Glycerin, 3. If fail Propylene glycol If it fails with glycerin, why should it work with propylene glycol?

     

    Because every compound has varying solubilities in various solvents.  Glycerin has different viscosity and chemical profile than PG. I am supposing certain things may not do well in Glycerin, but may do great in PG.



    Earlier:  Polymers: For max skin absorption: what do you think about: Gum arabic (it's used for oral drug delivery of lipophilic actives) vs Guar gum vs Chitosan vs Xanthan gum vs Sodium Hyaluronate.   How would each fare for dermal vs epidermal absorption? Absorption of what? An active or the polymer itself? Low molecular weight hyaluronic acid does penetrate to a degree, against all predictions and principles of skin penetration, though I'm not aware that this would help penetration of other ingredients in any regard. Same goes for a very few other polymers such as heparan. Chitisan, if properly formulated, may work, the others are just polymeric thickeners and gel builders.

    Wow, this is very informative.  I liked polymers since they are healthy.  Can ask your favorite compounds for this purpose?


    Short-term stability/preservation: citric acid, edta That's not preservation, that's chelation. Also, they are partially incompatible with chitosan and do not really contribute to physical stability.

     

    This part I do not understand.  I find Citric acid to extend shelf life.  EDTA I have experienced issues, but did not understand them well.   

    f) Is there something lacking in above. Yes, there is: some books on your shelf and a sound basic knowledge. Again, no offense

    Yes, I have been reading a lot.  You can tell it took me this long to catch up to your inputs. 


  • MarkBroussardMarkBroussard Member, Professional Chemist
    @DeepTitan

    Why don't you do some research on deformable niosomes and see if that presents a viable option for you.  But, if you are using a microneedling device, the solution coated on the microneedle will penetrate to some extent.
    Chemist/Microbiologist formulating in the Organic & Naturals & Clean Beauty arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program/Clean At Sephora/Credo Clean guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • DeepTitanDeepTitan Member
    edited September 21
    Is a 'niosome', just a minor variation to a standard liposome?  Publications they love to make their stuff appear overly complex and hard to understand (as if the work worthy of a nobel Laurette :).  Would a Niosome be like some extra ingredient that makes the liposome elastic or its more than that?  I usually add MCT oil in my liposomes, as in my experience for topical application, the lipsome gets a little oomph in penetration with MCT oil (though certain ingredients like chitosan, they don't like when I add mct oil).  I don't quite understand the science of it yet.
     
    You wrote: 
    Why don't you do some research on deformable niosomes


    That is a good tip.  
    You wrote:
    if you are using a microneedling device, the solution coated on the microneedle will penetrate to some extent
  • MicroformulationMicroformulation Member, Professional Chemist
    edited September 21
    You are overthinking the transdermal model of delivery. Generally, the actives are incorporated in light mineral oil and polyisobutylene. It depends upon the delivery of an active across a rate-controlling membrane from a higher concentration to a lower concentration. Pharmacokinetics come into play here.
    markfuller@microformulation.com Microformulation.com Microformulation Cosmetic Consulting provides Custom Formulations for both large Commercial accounts as well as smaller entrepreneurs. We can provide Naturally compliant Formulations under the NSF, NPA, Whole Foods and USDA Organic Certifications. BS.Pharm Albany College of Pharmacy, Union University.
  • MarkBroussardMarkBroussard Member, Professional Chemist
    @DeepTitan

    Niosomes are generally prepared using a non-ionic surfactant and cholesterol.  Niosomes are shape shifters ... the vesicle is not a rigid structure, but can change shape to enhance penetration.
    Chemist/Microbiologist formulating in the Organic & Naturals & Clean Beauty arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program/Clean At Sephora/Credo Clean guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • Thanks.  I searched for non-ionic surfactants.  Span 60 and Span 80 seems to be 2 choices.  Span 80 (aka Polysorbate 80) is easily available on Ebay/Amazon.  Span 60 (aka Sorbitan Monostearate), I don't see it for sale except SigmAldrich.  I am attracted to this Sorbitan Monostearate but sadly its not available.   I do have stearic acid flakes (they are a potent nutrition for mitochondria in cells). 

    a) By chance can I make equivalent to this Sorbitan Monostearate by mixing/heating stearic acid (since it comes solid) with some oil?  

    b) Between Span 80 or Span 60, which would be easy on skin (that is less tacky and more comfortable to keep on skin). 

    c) any other easy to find choice for non-ionic surfactants?

    Mark Broussard wrote:
    Niosomes are generally prepared using a non-ionic surfactant and cholesterol.  Niosomes are shape shifters ... the vesicle is not a rigid structure, but can change shape to enhance penetration
  • Thanks.  I do have mineral oil.  PolyIsoButylene I dont seem to find.  

    Microformulation wrote:
    You are overthinking the transdermal model of delivery. Generally, the actives are incorporated in light mineral oil and polyisobutylene. It depends upon the delivery of an active across a rate-controlling membrane from a higher concentration to a lower concentration. Pharmacokinetics come into play here.
  • DeepTitanDeepTitan Member
    edited September 22
    One more question sorry: would 'mango butter' (that predominates in stearic acid) fit into any of our talked about categories for niosomes? 
  • MicroformulationMicroformulation Member, Professional Chemist
    DeepTitan said:
    Thanks.  I do have mineral oil.  PolyIsoButylene I dont seem to find.  

    Microformulation wrote:
    You are overthinking the transdermal model of delivery. Generally, the actives are incorporated in light mineral oil and polyisobutylene. It depends upon the delivery of an active across a rate-controlling membrane from a higher concentration to a lower concentration. Pharmacokinetics come into play here.
    You also don't have a rate-limiting membrane. Also it depends upon concentration gradients and the pharmacokinetics. You wouldn't just "slap some on."

    markfuller@microformulation.com Microformulation.com Microformulation Cosmetic Consulting provides Custom Formulations for both large Commercial accounts as well as smaller entrepreneurs. We can provide Naturally compliant Formulations under the NSF, NPA, Whole Foods and USDA Organic Certifications. BS.Pharm Albany College of Pharmacy, Union University.
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