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Author: Subject: Polymeric Drug Delivery

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[*] posted on 23-7-2011 at 21:16
Polymeric Drug Delivery

Not sure if this is the appropriate sub-forum for a discussion on polymers, but here we goooo:

I've recently become pretty infatuated with the way some medicines are able to delay the release of their compound using a polymer matrix such as hypromellose. From my research today I've come across a few helpful links generalizing the mechanism behind it. One is: . Another couple sources were found via Google books, and my university EBSCO pass.

What I haven't been able to find is a picture or diagram or a thorough analysis / mechanism of exactly what happens. Generally the hydrophilic carrier (hypromellose) surrounds the medicine and swells after contact with water. The swelling then creates pours where the medicine can either diffuse out into the stomach or slide out through natural deterioration of the carrier polymer. I've included a really crude picture that helped me picture it a bit better.


If the carrier polymer was soluble in water (Hypromellose is not) and the medicine it surrounded was not soluble in water would that polymer effectively change the medicines properties temporarily and make it soluble? Or consider a soluble polymer covering an insoluble polymer. That might have been a dumb question / thought.

Then the addition of excipients and binders just makes things so confusing to visualize.

Any help clarifying or smacking me around with a large trout would be greatly appreciated. Thanks for your time. Sorry so verbose.

abcVeryhelpful.gif - 20kB

[Edited on 24-7-2011 by wightolore]
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[*] posted on 6-8-2011 at 10:16

Well, to start with: It is just as simple as diffusion/deterioration. Nothing fancy.
The trick is to formulate the carrier so that it will release the drug in the right rate. And yes, if you manage to put a hydrophobic drug into a hydrophilic carrier, it gets water soluble. I guess it will only exit the carrier when the carrier has contact to something hydrophobic, but I'm not sure.

Another interesting thing is guest/host-complexes of cyclodextrins. Cyclodextrins are barrel-shaped and relatively hydrophilic on the outside and relatively hydrophobic on the inside. Try and Google them!
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[*] posted on 6-8-2011 at 16:30

There is a lot of discussion on "tussicaps" in the drug related forums. It is a sulfonated styrene-divinylbenzene copolymer complexed with hydrocodone.

Pulled this from bluelight. 5th hit on google.
"It's due to an equilibrium between 'bound' hydrocodone sulphonate salt and 'free' hydrocodone hydrochloride formed by the action of stomach acids. It will reach a dynamic equilibrium based on the pKa (effectively how 'strong' an acid is) of the two acids.

So say at equilibrium, for every 3 molecules in the bound sulphonate form, there will 2 molecules as the hydrochloride salt; on to pf that, consider that the 'free' hydrochloride form is also being absorbed into the bloodstream. This reduces the number of molecules in the hydrochloride form, and to keep the equilibrium, some of the hydrocodone in the sulphonate salt form are released to form the hydrochoride salt. This process keeps on going until the all of the hydrocodone is released from the sulphonate polymer.

To get an instant release, the beads can be placed in a solution of a string alkali ion such as sodium hydroxide. As sodium hydroxide in solution is much more basic/alkaline than a soln of hydrocodone freebase in water, the sodium ions will displace the hydrocodone in a very short space of time (the difference in alkalinity between sodium hydroxide and hydrocodone freebase is a hell of a lot more than the difference in acidity between sulphonic acids and hydrochloric acid).

If the compound to be released isn't very soluble in freebase form, it may be necessary to use a sodium salt of a weak acid (such as sodium acetate - formed by the reaction between sodium bicarbonate and acetic acid), so that the compound released into solution forms the (soluble) acetate salt.
As sodium acetate isn't as alkaline in solution as sodium hydroxide, the exchange will take a bit longer to complete.

Absolute times for say 90 percent release depend upon a lot of factors such as temp., concentration of sodium salt and the pH of solution."

I cannot attest to the accuracy of this information.

[Edited on 7-8-2011 by Bot0nist]

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[*] posted on 6-8-2011 at 20:52

Well, ok, I wouldnt say it's nothing fancy cause if it were that easy, I'd have have my paper already *crosses fingers*

But as others have said, release is based on diffusion and/or deterioration of the carrier. The hardest part is finding the right carrier. Tuning the release once you found the good carrier is easy.

First the carrier must interact with the drug (hydrophobic interactions, ionic, convalent conjugation...). And then it has to interact strongly enough that it can go through the body and still be intact by the time it reaches the target. However, it cant be so strong that it doesnt release... This is very difficult.

And then you have to try to tune the feed ratios and solvent parameters to get the right particle size (particle size is very very important)

You have to consider why you want to encapsulate this drug in the first place? Because its non water soluble? Then you only need a soluble carrier or solublizer. Or is it because of horrible side effects from nonspecific delivery (for example in the case of chemotherapy)? In that case, adding a carrier has no benefit unless the carrier is more specific than the free drug. So for that, you might add a ligand to the polymer that will bind to receptors overexpressed by cancer cells.

And then probably the most important but least understood issue is, once the carrier is at the target organ, HOW does it enter the cell? Endocytosis? Disruption of cell membrane? If endocytosed, how does it escape from the endosome?

And then more clinical issues: Is the carrier biocompatible? Will it cause an immune response? How is it eliminated from the body? Will it interact and precipitate with blood proteins? Will it cause hemotoxicity? Etc...

So a billion factors are all working against eachtoerh when you are trying to find a drug carrier.... which is why I dont have my paper yet :(

Get a review article on polymeric drug delivery. It will explain a lot better than I can here.

[Edited on 8/7/2011 by Saerynide]

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