Liberation is the first step in the process by which medication enters the body and liberates the

active ingredient An active ingredient is any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. The ...

that has been administered. The

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

must separate from the

vehicle A vehicle (from la, vehiculum) is a machine that transports people or cargo. Vehicles include wagons, bicycles, motor vehicles (motorcycles, cars, trucks, buses, mobility scooters for disabled people), railed vehicles (trains, trams), ...

or the

excipient An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

that it was mixed with during manufacture. Some authors split the process of liberation into three steps: disintegration, disaggregation and dissolution. A limiting factor in the adsorption of pharmaceutical drugs is the degree to which they are ionized, as cell membranes are relatively impermeable to ionized molecules. The characteristics of a medication's excipient play a fundamental role in creating a suitable environment for the correct absorption of a drug. This can mean that the same dose of a drug in different forms can have different

bioequivalence Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all ...

, as they yield different plasma concentrations and therefore have different therapeutic effects.

Dosage form Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a ca ...

s with modified release (such as delayed or extended release) allow this difference to be usefully applied.

Dissolution

In a typical situation, a pill taken orally will pass through the

oesophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to th ...

and into the

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

. As the stomach has an aqueous environment, it is the first place where the pill can dissolve. The rate of dissolution is a key element in controlling the duration of a drug's effect. For this reason, different forms of the same medication can have the same active ingredients but different dissolution rates. If a drug is administered in a form that is not rapidly dissolved, the drug will be absorbed more gradually over time and its action will have a longer duration. A consequence of this is that patients will comply more closely to a prescribed course of treatment, if the medication does not have to be taken as frequently. In addition, a slow release system will maintain drug concentrations within a therapeutically acceptable range for longer than quicker releasing delivery systems as these result in more pronounced peaks in plasma concentration. The dissolution rate is described by the

Noyes–Whitney equation Arthur Amos Noyes (September 13, 1866 – June 3, 1936) was an American chemist, inventor and educator. He received a PhD in 1890 from Leipzig University under the guidance of Wilhelm Ostwald. He served as the acting president of MIT between ...

\frac = \frac

Where: *

\frac

is the dissolution rate. * A is the solid's surface area. * C is the concentration of the solid in the bulk dissolution medium. *

C_

is the concentration of the solid in the

diffusion Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...

layer surrounding the solid. * D is the diffusion coefficient. * L is the thickness of the

diffusion layer In electrochemistry, the diffusion layer, according to IUPAC, is defined as the "region in the vicinity of an electrode where the concentrations are different from their value in the bulk solution. The definition of the thickness of the diffusion la ...

. As the solution is already in a dissolved state, it does not have to go through a dissolution stage before absorption begins.

Ionization

Cell membranes present a greater barrier to the movement of ionized molecules than non-ionized liposoluble substances. This is particularly important for substances that are weakly

amphoteric In chemistry, an amphoteric compound () is a molecule or ion that can react both as an acid and as a base. What exactly this can mean depends on which definitions of acids and bases are being used. One type of amphoteric species are amphipro ...

. The stomach's acidic pH and the subsequent alkalization in the intestine modifies the degree of ionization of acids and weak bases depending on a substance's pKa.Simonetta Baroncini, Antonio Villani, Gianpaolo Serafini
Anestesia neonatal y pediátrica
' (in Spanish). Published by

Elsevier Elsevier () is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell'', the ScienceDirect collection of electronic journals, '' Trends'', th ...

España, 2006; page 19. The pKa is the pH at which a substance is present at an equilibrium between ionized and non-ionized molecules. The

Henderson–Hasselbalch equation In chemistry and biochemistry, the Henderson–Hasselbalch equation :\ce = \ceK_\ce + \log_ \left( \frac \right) relates the pH of a chemical solution of a weak acid to the numerical value of the acid dissociation constant, ''K''a, of acid and th ...

is used to calculate pKa.

References

{{Pharmacology Pharmacokinetics

Dissolution

Ionization

See also

References