Absorption is the journey of a drug travelling from the site of administration to the site of action.
The drug travels by some
route of administration (
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or or ...
,
topical-dermal, etc.) in a chosen
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 ...
(e.g.,
tablets,
capsules, or in
solution
Solution may refer to:
* Solution (chemistry), a mixture where one substance is dissolved in another
* Solution (equation), in mathematics
** Numerical solution, in numerical analysis, approximate solutions within specified error bounds
* Soluti ...
).
Absorption by some other routes, such as
intravenous therapy,
intramuscular injection,
enteral nutrition
Enteral administration is food or drug administration via the human gastrointestinal tract. This contrasts with parenteral nutrition or drug administration (Greek ''para'', "besides" + ''enteros''), which occurs from routes outside the GI tract, ...
, is even more straightforward and there is less variability in absorption and
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
is often near 100%.
Intravascular
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...
administration does not involve absorption, and there is no loss of drug. The fastest route of absorption is
inhalation.
Absorption is a primary focus in
drug development
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for re ...
and
medicinal chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...
, since a drug must be absorbed before any medicinal effects can take place. Moreover, the drug's pharmacokinetic profile can be easily and significantly changed by adjusting factors that affect absorption.
Dissolution
In the most common situation, a tablet is ingested and passes through the
esophagus
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 ...
to 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 ...
.
The rate of dissolution is a key target for controlling the duration of a drug's effect, and as such, several dosage forms that contain the same active ingredient may be available, differing only in the rate of dissolution. If a drug is supplied in a form that is not readily dissolved, it may be released more gradually and act for longer. Having a longer duration of action may improve
compliance since the medication will not have to be taken as often. Additionally, slow-release dosage forms may maintain concentrations within an acceptable therapeutic range over a long period of time, whereas quick-release dosage forms may have sharper peaks and troughs in serum concentration.
The rate of dissolution 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 ...
as shown below:
:
Where:
*
is the rate of dissolution.
*A is the
surface area of the solid.
*C is the concentration of the solid in the bulk dissolution medium.
*
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 chemica ...
layer surrounding the solid.
*D is the diffusion
coefficient.
*L is 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 ...
thickness.
As can be inferred from the Noyes–Whitney equation, the rate of dissolution may be modified primarily by altering the surface area of the solid, by altering the particle size (e.g. with
micronization
Micronization is the process of reducing the average diameter of a solid material's particles. Traditional techniques for micronization focus on mechanical means, such as milling and grinding. Modern techniques make use of the properties of supe ...
). For many drugs, reducing the particle size leads to a reduction in the dose needed to achieve the same therapeutic effect. The reduction of particle size increases the
specific surface area
Specific surface area (SSA) is a property of solids defined as the total surface area of a material per unit of mass, (with units of m2/kg or m2/g) or solid or bulk volume (units of m2/m3 or m−1).
It is a physical value that can be used to dete ...
and the dissolution rate, and it does not affect solubility.
The rate of dissolution may also be altered by choosing a suitable
polymorph of a compound. Different polymorphs have different solubility and dissolution rate characteristics. Specifically, crystalline forms dissolve slower than amorphous forms, since they require more energy to leave lattice during dissolution. The stablest crystalline polymorph has the lowest dissolution rate. Dissolution also differs between anhydrous and hydrous forms of a drug. Anhydrous forms often dissolve faster, but sometimes are less soluble.
Esterification
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
is also used to control solubility. For example,
stearate and
estolate ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
s of drugs have decreased solubility in
gastric fluid
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...
. Later,
esterase
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.
A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...
s in the
gastrointestinal tract (GIT) wall and blood
hydrolyze
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
these esters to release the parent drug.
Coatings on a tablet or pellet may act as barriers to reduce the rate of dissolution. Coatings may also be used to control where dissolution takes place. For example,
enteric coating An enteric coating is a polymer barrier applied to oral medication that prevents its dissolution or disintegration in the gastric environment. This helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental ef ...
s only dissolve in the
basic environment of the
intestines
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
.
Drugs held in solution do not need to be dissolved before being absorbed.
Lipid-soluble drugs are absorbed more rapidly than water-soluble drugs.
Ionization
The
gastrointestinal tract is lined with
epithelial cells. Drugs must pass through or permeate these cells to be absorbed into the
bloodstream
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
.
Cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s may act as barriers to some drugs. They are essentially
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
s which form
semipermeable membranes. Pure lipid bilayers are generally permeable only to small, uncharged solutes. Hence, whether or not a molecule is
ionized
Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecule ...
will affect its absorption, since ionic molecules are charged. Solubility favors charged species, and permeability favors neutral species. Some molecules have special exchange proteins and channels to facilitate movement from the lumen into the circulation.
Ions cannot passively diffuse through the gastrointestinal tract because the epithelial cell membrane is made up of a
phospholipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
, comprising two layers of phospholipids in which the charged hydrophilic heads face outwards and the uncharged hydrophobic fatty acid chains are in the middle of the layer. The fatty acid chains repel ionized, charged molecules. This means that the ionized molecules cannot pass through the intestinal membrane and be absorbed.
The
Henderson-Hasselbalch equation offers a way to determine the proportion of a substance that is ionized at a given pH. In the stomach, drugs that are
weak acid
Acid strength is the tendency of an acid, symbolised by the chemical formula HA, to dissociate into a proton, H+, and an anion, A-. The dissociation of a strong acid in solution is effectively complete, except in its most concentrated solutions ...
s (such as
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
) will be present mainly in their non-ionic form, and
weak base
A weak base is a base that, upon dissolution in water, does not dissociate completely, so that the resulting aqueous solution contains only a small proportion of hydroxide ions and the concerned basic radical, and a large proportion of undissociat ...
s will be in their ionic form. Since non-ionic species diffuse more readily through
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s, weak acids will have a higher absorption in the highly acidic
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 ...
.
However, the reverse is true in the
basic environment of the intestines—weak bases (such as
caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
) will diffuse more readily since they will be non-ionic.
This aspect of absorption has been targeted by medicinal chemists. For example, they may choose an
analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
that is more likely to be in a non-ionic form. Also, the chemists may develop
prodrugs of a compound—these chemical variants may be more readily absorbed and then metabolized by the body into the active compound. However, changing the structure of a molecule is less predictable than altering dissolution properties, since changes in chemical structure may affect the
pharmacodynamic properties of a drug.
The solubility and permeability of a drug candidate are important physicochemical properties the scientist wants to know as early as possible.
Other factors
Absorption also varies depending on bioactivity, resonance, the inductive effect, isosterism, bio-isosterism, and consideration, amongst others.
Types
Types of absorption in pharmacokinetics include the following:
* Instantaneous absorption: absorption is nearly immediate. A common example is bolus
intravenous injection.
* Zero-order absorption: rate of absorption is constant. A common example is continuous
intravenous infusion
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
.
* First-order absorption: rate of absorption is proportional to the amount of drug remaining to be absorbed. Representative examples include typical cases of
oral administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...
,
subcutaneous injection, and
intramuscular injection.
See also
*
Gastrointestinal transit time
*
Flip–flop kinetics Flip–flop kinetics, or flip–flop pharmacokinetics, describes an atypical situation in pharmacokinetics where a drug's rate of absorption or the rate at which it enters the bloodstream is slower than its elimination rate. That is, when the ''k ...
References
Further reading
*
External links
Absorption of Drugs
{{Pharmacology
Pharmacology
Pharmacokinetics