How solubilization affects bioavailability

17 October 2022 — by F.D.  

How well an active ingredient in a drug is absorbed by the body depends on various factors. The form of administration has a major influence on this - absorption is significantly poorer with oral administration than with intravenous administration. However, the way in which the active ingredient is contained in the preparation also plays a major role. For example, the absorption of the active ingredient can be significantly improved by the solubilization process.

How solubilization affects bioavailability

Bioavailability of the active ingredient

When you are administering medication, the medicine's active ingredient should reach the intended site of action in the patient's body in order to develop its effect there. But this is not always easy - depending on the dosage form, some is lost en route, whether through metabolism, excretion, lack of absorption or the "first-pass effect." Bioavailability is a term used in pharmacology and is a measure of how much active ingredient actually reaches the patient. In other words, it describes how quickly and to what extent an active ingredient is absorbed and is available at the site of action. The more of the active ingredient is absorbed unchanged and reaches the systemic circulation, the higher the bioavailability of the administered drug. The bioavailability of medicines is an important measure for correct dosing. If only 50% of the active ingredient can be absorbed, the dosage must be doubled accordingly.

Die Bioverfügbarkeit der Inhaltsstoffe kann durch Solubilisierung erhöht werden.

Die Bioverfügbarkeit der Inhaltsstoffe kann durch Solubilisierung erhöht werden.

How the dosage form influences bioavailability

The route by which a drug enters the body has a major influence on its bioavailability. By definition, intravenously administered drugs have a bioavailability of 100%. This is due to the fact that bioavailability is measured by determining the concentration of the active ingredient in the blood plasma at different times after ingestion - with intravenous administration, 100% of the active ingredient is in the systemic circulation immediately after administration and is therefore available to the organism. Intravenous administration, however, also results in rapid degradation of the active substance.

When administered intramuscularly, the overall bioavailability is lower and it takes longer for the active ingredient to reach the blood plasma. The plasma concentration increases slowly and the active substance is available to the organism for longer. The bioavailability is generally lowest when a drug is administered orally. On the other hand, the active ingredient is absorbed slowly and the concentration remains high for a longer period of time.

The difficulty of oral administration

When administered orally, a drug is absorbed via the digestive tract. The bioavailability is generally rather low, as the active ingredient has to overcome several hurdles before it can reach its site of action in the blood plasma.

  • Gastric acid: Right from the start, it makes the active ingredient having to work hard. The stomach has a very acidic environment (pH value: 1-2), which can dissolve drugs into their components and destroy molecular structures. If the active ingredient is not protected, a lot is already lost here.
  • Digestive enzymes: Lots of enzymes in the gastrointestinal tract are just waiting to do what they do best: Split molecules into their individual parts. This is extremely unfavorable for an active ingredient that needs to enter the bloodstream as completely as possible.
  • Excretion: Much of what is taken orally is simply excreted again directly - either via the kidneys or directly via the intestines. The active ingredient is often metabolized before excretion.
  • First-pass effect: Once an active ingredient has actually managed to be absorbed by the enterocytes and enter the bloodstream, it is transported to the liver via the portal vein. And here it is once again properly filtered out: due to metabolization in the liver cells, only a small proportion of the active ingredient that has arrived reaches the inferior vena cava and is ultimately actually available.
How solubilization affects bioavailability

Various tricks are used to increase the bioavailability of oral medications. Hard capsules are often used to protect active ingredients from stomach acid and the first digestive enzymes. For some active ingredients, it can also be helpful if they are partially absorbed via the oral mucosa and thus enter the circulation directly. The process of solubilization simplifies this absorption, also protects during the passage through the stomach and facilitates absorption into the enterocytes.

What is "solubilization"?

An unwieldy word that conceals a process for significantly increasing bioavailability. The active ingredients in a preparation are finely dispersed and completely dissolved in a carrier oil using an emulsifier. You can imagine that the entire active ingredient is not in a heap, but that many individual active ingredient particles are distributed in the carrier oil. The emulsifier ensures that this remains the case: It places itself between the active ingredient particles in such a way that they cannot stick together again. The result is a complete solution.

Influencing the bioavailability

A solution with solubilized ingredients is called a solubilizate – and this has advantages for the absorption of active ingredients.

When the oily preparation comes into an aqueous environment, such as saliva, the active ingredient particles are surrounded by emulsifiers and form tiny vesicles: A microemulsion is created.

The vesicles protect the active ingredients from digestive enzymes and gastric juice. Absorption into the cells is also significantly facilitated because the outer shell of the vesicles is similar to the body's own biomembranes: the vesicles can fuse with cell membranes and thus transport their cargo into the interior of the cell.

Bioavailability can be greatly increased by solubilization - especially because solubilizates can also be absorbed through the oral mucosa. When the medicine comes into contact with the moist mucous membranes, the aforementioned vesicles are formed immediately, which do not have to pass through the digestive tract first - their similarity to the body's own biomembranes means that they can be absorbed on the spot and enter the bloodstream. This saves the challenging route through the digestive tract and avoids the first-pass effect of the liver.

If a solubilizate is swallowed, the bioavailability is also increased: The vesicles protect against digestive enzymes and stomach acid and facilitate absorption into the enterocytes and the systemic circulation. What is contained in solubilized preparations therefore actually reaches the body.

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