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If a chemical is ingested (supplement or drug) orally, which is insoluble in water, how can it be absorbed into the body? Is there something inside a capsule that the compound is mixed with?

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    $\begingroup$ Think of this: fat is insoluble as well, yet you may eat fat, and it will get digested. How so? $\endgroup$ – Ivan Neretin Sep 25 '15 at 21:22
  • $\begingroup$ I'm fat in general, so maybe I'm capable of absorbing anything. :-) Is there a chemical reaction in our stomach that turns fat into something else so we can absorb it. I do know a person with Colitis can absorb a lot more than usual, not to their benefit. Especially MSG, gluten, chemicals that cause chemical imbalances (from MacDonalds, Dunkin Donuts, Burger King, etc..), etc... $\endgroup$ – MacGyver Sep 25 '15 at 21:44
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    $\begingroup$ Long story short, we've been able to absorb fats way before any supplements or drugs came along (and way before we became humans, too). The digestive enzymes in the bile split the fats into a fine emulsion and work on them. Here my knowledge becomes somewhat patchy. Let someone with the better grasp write an answer. $\endgroup$ – Ivan Neretin Sep 25 '15 at 21:47
  • $\begingroup$ +1, thanks Ivan! I just found some good material after some reading. Processing a chemical to be "water solubilized" seems to be how they do it. According to some material I found, Vitamin E needs to have this done during manufacturing. Whereas Vitiman B and C, are naturally water soluble. Hopefully we get a response. $\endgroup$ – MacGyver Sep 25 '15 at 22:35
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    $\begingroup$ Thanks :P I just checked its solubility, <0.1g per 100ml, in high school inorganic chemistry you'll be told it's insoluble, but as a fat-soluble vitamin(which means low daily intake requirement) it seems well enough for supplementary purposes. $\endgroup$ – busukxuan Oct 2 '15 at 9:59
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Well, firstly the capsule itself is not entirely insoluble. You can see this for yourself - if you drop one into water, it will start to dissolve very slowly and the water will turn cloudy. This process usually goes faster in the stomach, which has a very acidic environment, or the small intestine which is more alkaline. The capsule material is designed to dissolve when it's eaten, hence releasing the drug - if it didn't dissolve, the whole capsule would just pass through your digestive system and come out... at the other end.

On to the issue about the drug itself. In general designing a drug is not very simple at all, because it has to survive the very same enzymes that break down our food - if the enzymes break down the drug then it becomes useless. For example, if you tried to eat insulin it wouldn't do you any good - insulin is a protein and will be immediately digested by protease enzymes. If the drug survives those enzymes, it has to be able to diffuse through the lining of the small intestine in order for it to enter the bloodstream. The cell membrane, being a non-polar lipid bilayer, doesn't easily let polar or charged molecules diffuse across it. So normally drugs have to be somewhat lipophilic, which is a fancy way of saying non-polar. But at the same time, as you rightly note, they also have to be water-soluble. Most drugs try to strike a balance between the two.

One way that drugs are absorbed is by reversible protonation. Many drugs have amine functional groups with a $\text{p}K_{\text{aH}}$ of around 6-8. At the physiological pH of 7.4, an equilibrium will exist in which both the unprotonated and protonated forms exist in significant amounts. The unprotonated form can cross cell membranes more easily, and the protonated form is more soluble in water.

There are other drugs that don't diffuse across cell membranes very well, due to their large polarity. They may be absorbed via different means, such as active transport (in which the cell uses energy in order to let the molecule enter), or facilitated diffusion (which is the same as diffusion, except that a protein helps out). An example is levodopa; it is structurally similar to the amino acid phenylalanine and the transport protein for phenylalanine can't quite tell the difference. Being polar molecules, these drugs are already water-soluble.

In fact, that's only half the story, because different drugs have different targets. Some need to go to the brain and for this to happen, they have to cross the blood-brain barrier. Some need to stay in the intestines to kill off bacteria - so you have to make them really polar so that they can't diffuse into the bloodstream. Absorption is only a small part of a drug's journey in the human body. If you are interested in finding out more, look for a textbook on medicinal chemistry and read the section about pharmacokinetics - it should have all the info you want.

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    $\begingroup$ Not to forget, some if not most capsules are digestible, not just soluble. Many are made of protein or starch, which can be digested into amino acids and glucose, thereby releasing the drug within. $\endgroup$ – busukxuan Oct 2 '15 at 8:57
  • $\begingroup$ @busukxuan cool - didn't know that :) $\endgroup$ – orthocresol Oct 2 '15 at 9:01
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Apart from acknowledging orthocresol’s fine answer, allow me to add that nothing is ever entirely insoluble in something else. There is always entropy to be gained by having just a few molecules of A diffuse into B, so tiny bits of (say) hexane will end up in water.

Hexane and water are extreme examples here. Most drugs are designed to be somewhat semi-polar as are most hallucinogenics (albeit not necessarily designed). They will dissolve in aquaeous solvents well enough to be taken up. One often teaches solubility as black-and-white, when in reality it should be millions of shades of grey.

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Compounds like organic amines, which are basic and would be insoluble in water are very often turned into water soluble salts by treating them with acid yielding hydrochloride salts, sulfates, citrates and so on. Examples include ephedrine and methyl phenidate, both of which are marketed as hydrochloride salts in Europe.

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    $\begingroup$ OP's asking about things which are used despite being insoluble... $\endgroup$ – Mithoron Sep 27 '15 at 22:40
  • $\begingroup$ What is "OP"? .. $\endgroup$ – MacGyver Oct 2 '15 at 23:14

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