Absorption (pharmacology)

Last updated

Absorption is the journey of a drug travelling from the site of administration to the site of action. [1] [2]

Contents

The drug travels by some route of administration (oral, topical-dermal, etc.) in a chosen dosage form (e.g., tablets, capsules, or in solution). [3] Absorption by some other routes, such as intravenous therapy, intramuscular injection, enteral nutrition, is even more straightforward and there is less variability in absorption and bioavailability is often near 100%. Intravascular administration does not involve absorption, and there is no loss of drug. [4] The fastest route of absorption is inhalation. [5]

Absorption is a primary focus in drug development and medicinal chemistry, 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

Oral ingestion is the most common route of administration of pharmaceuticals. [6] Passing through the esophagus to the stomach, the contents of the capsule or tablet are absorbed by the GI tract. The absorbed pharmaceutical is then passed through the liver and kidneys. [7]

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 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 longer period, whereas quick-release dosage forms may have sharper peaks and troughs in serum concentration. [8]

The rate of dissolution is described by the Noyes–Whitney equation as shown below:

Where:

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). For many drugs, reducing the particle size reduces the dose needed to achieve the same therapeutic effect. The particle size reduction increases the specific surface area and the dissolution rate and 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 the 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 is also used to control solubility. For example, stearate and estolate esters of drugs have decreased solubility in gastric fluid. Later, esterases in the gastrointestinal tract (GIT) wall and blood hydrolyze these esters to release the parent drug.

Coatings on a tablet or pellet may act as barriers to reducing the dissolution rate. Coatings may also be used to control where dissolution takes place. For example, enteric coatings only dissolve in the basic environment of the intestines.

Drugs held in solution do not need to be dissolved before being absorbed.

Lipid-soluble drugs are absorbed more rapidly than water-soluble drugs. [9]

Ionization

The gastrointestinal tract is lined with epithelial cells. Drugs must pass through or permeate these cells to be absorbed into the bloodstream. Cell membranes may act as barriers to some drugs. They are essentially lipid bilayers which form semipermeable membranes. Pure lipid bilayers are generally permeable only to small, uncharged solutes. Hence, whether or not a molecule is ionized 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.[ vague ]

Ions cannot passively diffuse through the gastrointestinal tract because the epithelial cell membrane is made up of a phospholipid bilayer, 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 acids (such as aspirin) will be present mainly in their non-ionic form, and weak bases will be in their ionic form. Since non-ionic species diffuse more readily through cell membranes, weak acids will have a higher absorption in the highly acidic stomach.

However, the reverse is true in the basic environment of the intestines—weak bases (such as caffeine) 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 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. [10]

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: [11]

See also

Related Research Articles

<span class="mw-page-title-main">Route of administration</span> Path by which a drug, fluid, poison, or other substance is taken into the body

In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.

In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; the terms are equivalent in the literature. Larger structures such as nucleic acids and proteins, and many polysaccharides are not small molecules, although their constituent monomers are often considered small molecules. Small molecules may be used as research tools to probe biological function as well as leads in the development of new therapeutic agents. Some can inhibit a specific function of a protein or disrupt protein–protein interactions.

In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.

In the physical sciences, a partition coefficient (P) or distribution coefficient (D) is the ratio of concentrations of a compound in a mixture of two immiscible solvents at equilibrium. This ratio is therefore a comparison of the solubilities of the solute in these two liquids. The partition coefficient generally refers to the concentration ratio of un-ionized species of compound, whereas the distribution coefficient refers to the concentration ratio of all species of the compound.

<span class="mw-page-title-main">ADME</span> Acronym for process of disposition of pharmaceutical compounds

ADME is the four-letter abbreviation (acronym) for absorption, distribution, metabolism, and excretion, and is mainly used in fields such as pharmacokinetics and pharmacology. The four letter stands for descriptors quantifying how a given drug interacts within body over time. The term ADME was first introduced in 1960s, and has become a standard term widely used in scientific literature, teaching, drug regulations, and clinical practice.

<span class="mw-page-title-main">Topical medication</span> Medication applied to body surfaces

A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word topical derives from Greek τοπικόςtopikos, "of a place".

<span class="mw-page-title-main">Methylprednisolone</span> Corticosteroid medication

Methylprednisolone is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.

Sublingual, from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue.

<span class="mw-page-title-main">Enteral administration</span>

Enteral administration is food or drug administration via the human gastrointestinal tract. This contrasts with parenteral nutrition or drug administration, which occurs from routes outside the GI tract, such as intravenous routes. Enteral administration involves the esophagus, stomach, and small and large intestines. Methods of administration include oral, sublingual, and rectal. Parenteral administration is via a peripheral or central vein. In pharmacology, the route of drug administration is important because it affects drug metabolism, drug clearance, and thus dosage. The term is from Greek enteros 'intestine'.

Skin absorption is a route by which substances can enter the body through the skin. Along with inhalation, ingestion and injection, dermal absorption is a route of exposure for toxic substances and route of administration for medication. Absorption of substances through the skin depends on a number of factors, the most important of which are concentration, duration of contact, solubility of medication, and physical condition of the skin and part of the body exposed.

Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.

Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body.

Dose dumping is a phenomenon of drug metabolism in which environmental factors can cause the premature and exaggerated release of a drug. This can greatly increase the concentration of a drug in the body and thereby produce adverse effects or even drug-induced toxicity.

In cell biology, ion trapping is the build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane. This results in basic chemicals accumulating in acidic bodily fluids such as the cytosol, and acidic chemicals accumulating in basic fluids.

<span class="mw-page-title-main">Oral administration</span> Route of administration where a substance is taken through the mouth

Oral administration is a route of administration whereby a substance is taken through the mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications.

An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol with increased resistance to first-pass metabolism, slightly improving its oral bioavailability. In addition, estrogen esters have increased lipophilicity, which results in a longer duration when given by intramuscular or subcutaneous injection due to the formation of a long-lasting local depot in muscle and fat. Conversely, this is not the case with intravenous injection or oral administration. Estrogen esters are rapidly hydrolyzed into their parent estrogen by esterases once they have been released from the depot. Because estradiol esters are prodrugs of estradiol, they are considered to be natural and bioidentical forms of estrogen.

Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism. Drug forms for buccal administration include tablets and thin films.

Liberation is the first step in the process by which medication enters the body and liberates the active ingredient that has been administered. The pharmaceutical drug must separate from the vehicle or the excipient 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.

<span class="mw-page-title-main">Furegrelate</span> Chemical compound

Furegrelate, also known as 5-(3-pyridinylmethyl)benzofurancarboxylic acid, is a chemical compound with thromboxane enzyme inhibiting properties that was originally developed by Pharmacia Corporation as a drug to treat arrhythmias, ischaemic heart disorders, and thrombosis but was discontinued. It is commercially available in the form furegrelate sodium salt.

Topical drug delivery (TDD) is a route of drug administration that allows the topical formulation to be delivered across the skin upon application, hence producing a localized effect to treat skin disorders like eczema. The formulation of topical drugs can be classified into corticosteroids, antibiotics, antiseptics, and anti-fungal. The mechanism of topical delivery includes the diffusion and metabolism of drugs in the skin. Historically, topical route was the first route of medication used to deliver drugs in humans in ancient Egyptian and Babylonian in 3000 BCE. In these ancient cities, topical medications like ointments and potions were used on the skin. The delivery of topical drugs needs to pass through multiple skin layers and undergo pharmacokinetics, hence factor like dermal diseases minimize the bioavailability of the topical drugs. The wide use of topical drugs leads to the advancement in topical drug delivery. These advancements are used to enhance the delivery of topical medications to the skin by using chemical and physical agents. For chemical agents, carriers like liposomes and nanotechnologies are used to enhance the absorption of topical drugs. On the other hand, physical agents, like micro-needles is other approach for enhancement ofabsorption. Besides using carriers, other factors such as pH, lipophilicity, and drug molecule size govern the effectiveness of topical formulation.

References

  1. Alsanosi, Safaa Mohammed M.; Skiffington, Craig; Padmanabhan, Sandosh (2014). "Pharmacokinetic Pharmacogenomics". Handbook of Pharmacogenomics and Stratified Medicine. Elsevier. pp. 341–364. doi:10.1016/b978-0-12-386882-4.00017-7. ISBN   978-0-12-386882-4.
  2. Yang, Y.; Zhao, Y.; Yu, A.; Sun, D.; Yu, L.X. (2017). "Oral Drug Absorption". Developing Solid Oral Dosage Forms. Elsevier. pp. 331–354. doi:10.1016/b978-0-12-802447-8.00012-1. ISBN   978-0-12-802447-8.
  3. LE.JENNIFER (2020-03-27). "Drug Absorption - Clinical Pharmacology". MSD Manual Professional Edition. Retrieved 2020-03-28.
  4. Kaplan Pharmacology 2010, page 6, Absorption
  5. Kaplan Pharmacology 2010, Video Lectures, Absorption chapter
  6. Shimizu, Shinya. "Routes of administration" (PDF). The Laboratory Mouse. 1: 527–543.
  7. Jean, Kim; Orlando, Jesus. "Medication Routes of Administration". StatPearls Publishing. 1: 121–141.
  8. Ermer, James (2007). "Bioavailability of triple-bead mixed amphetamine salts compared with a dose-augmentation strategy of mixed amphetamine salts extended release plus mixed amphetamine salts immediate release". Current Medical Research and Opinion. 23 (5): 1067–1075. doi:10.1185/030079907x182095. PMID   17519073. S2CID   22893348.
  9. Mayor, Susan (2017). "Pharmacokinetics: Optimising safe and effective prescribing". Prescriber. 28 (3): 45–48. doi: 10.1002/psb.1551 . S2CID   79073985.
  10. Curatolo, William (1 December 1998). "Physical chemical properties of oral drug candidates in the discovery and exploratory development settings". Pharmaceutical Science & Technology Today. Elsevier. 1 (9): 387–393. doi:10.1016/S1461-5347(98)00097-2 . Retrieved 21 July 2021.
  11. Miles Hacker; William S. Messer; Kenneth A. Bachmann (19 June 2009). Pharmacology: Principles and Practice. Academic Press. pp. 212–. ISBN   978-0-08-091922-5.

Further reading