A-Z Glossary
Browse through the list of keywords and concepts that play a major role in the PEARRL project. If you have questions regarding the explanation or want to receive some more detailed explanation, do not hesitate to leave a comment in the section below.
ACAT model
Advanced Compartment Absorption and Transit Model (ACAT model) is a mathematical model that simulates oral drug absorption of drugs, based on the compartmental absorption and transit (CAT) model. The model assumes linear transfer kinetics through the gastro-intestinal compartments and non-linear kinetics for metabolic processes. The gastro-intestinal tract is composed of nine compartments (stomach, 7 compartments for the small intestine, and colon), in which the drug appears in six possible states (unreleased, undissolved, dissolved, degraded, metabolized, and absorbed); the excreted material can be found in three states (unreleased, dissolved, and undissolved). The model takes into account the drug physico-chemical properties, physiological factors, and dosage characteristics for the prediction of oral drug absorption. The model is included in the PBPK modelling platform Gastroplus®.
Amorphous state
Usually solids are crystalline, meaning that their molecules exhibit a long-range order (crystal lattice). Materials that lack this long-range order are called amorphous and they show increased solubility compared to their crystalline counterparts. This increased solubility has been linked to higher bioavailability for pharmaceutical molecules, as they enable higher concentrations in the GI lumen. Consequently, amorphisation has been extensively used as a bio-enabling formulation approach.
API
Active Pharmaceutical Ingredient
BCS
BCS stands for Biopharmaceutical Classification System and is a system proposed by Amidon et al. to classify drug substances based on their solubility and permeability properties. According to the BCS drug substances are classified into four classes: Class I - high permeability, high solubility, Class II - high permeability, low solubility, Class III - low permeability, high solubility, Class IV - low permeability, low solubility.
Bio-enabling formulation
Bio-enabling formulations are drug delivery technologies specially designed to expedite the release and subsequently absorption of poorly soluble drugs.
Bioavailability
Bioavailability is the fraction of administered drug entering the systemic circulation. For oral administered drugs, bioavailability will be composed of absorption and first pass metabolism.
Bioequivalence
Bioequivalence is a clinical term referring to formulations of a drug with rates and extents of absorption that were shown to be sufficiently similar during in vivo clinical trials in healthy volunteers. If two products are said to be bioequivalent it means that they would not have any clinically important differences with respect to either efficacy or safety.
Brick dust molecules
The term ‘brick dust’ is commonly used to describe compounds that have a poor solubility in water due to their strong crystal structure. Most ‘brick dust’ molecules exhibit a high melting point, high crystal lattice energy and consequently show pronounced hydrophobic physico-chemical properties. In some cases, the solubility of ‘brick dust’ molecules is also referred to as ‘solid state limited’ or ‘crystal lattice limited’. To promote dissolution of such molecules bio-enabling formulations are needed.
Dissemination
The public disclosure of the results by any appropriate means (other than resulting from protecting or exploiting the results).
Equilibrium solubility
Concentration of drug in a saturated solution when excess solid is present, and solution and solid are at equilibrium.
Exploitation
Using and recognising exploitable results and their stakeholders for further research activities other than those covered by the action concerned, or in developing, creating and providing a product, process, service or standardisation activities.
Fasted state
In oral drug absorption studies, it refers to the period immediately after a glass of water until the consumption of the next meal. The water should be consumed approximately 12 hours after the last meal.
Fed state
In oral drug absorption studies, it refers to the period 30 minutes after the start of consumption of a high-fat, high-calorie (800-1000 kcal) meal until the stomach is practically emptied from meal components. In addition, the meal should be consumed approximately 12 hours after the last one.
Food effects
Food effects on drug absorption are observed when the rate and/or extent of drug bioavailability is altered when a drug or drug product is administered in fed state, compared to the fasted state.
Grease ball molecules
The term grease ball was established to describe certain characteristics that lead to poor water solubility of drug substances. Such molecules exhibited limited solvation upon aqueous dispersion due to high lipophilicity. The physico-chemical properties of such molecules are often dominated by a high water-octanol partitioning coefficient and a moderate melting point. Certain pharmaceutical techniques are necessary to improve the solubility of such molecules.
Hot Melt Extrusion
Hot melt extrusion is a technique that is used for processing poorly water-soluble drugs. During this process, a powderous formulation mixture consisting mostly of drug and polymer is melted while being transported through a heated barrel. At the end of the barrel the molten mixture is pressed through a die and solidifies. Such process leads to an equally distributed drug substance in a polymeric matrix enhancing the bioavailability of the drug.
IVIVC
IVIVC stands for In vitro-In vivo correlation which is a mathematical model that enables the correlation of an in vitro trait to the in vivo performance of a drug dosage form. Usually, the In vitro input is the in vitro dissolution profile of the dosage form. IVIVC serves as a predictive tool for the in vivo behavior of dosage forms after possible changes in formulation.
Lipolysis model
Lipolysis models or in vitro digestion models are important tools for understanding the mechanisms behind drug compound flow between the different colloidal phases to an absorbable form after oral administration of lipid based-formulations. It is essential that the experimental setup of such models is representative for the physiological conditions in order to obtain useful information regarding the in vivo fate of the formulation.
Mesoporous Silica
Mesoporous silica is a relatively new bioenabling formulation. Originally applied in chromatographic separation, mesoporous silica is silica synthesised in combination with a template such that a porous (mesopores = 2-50nm) network remains. This porous network is highly functional. For enabling formulations, solubilized API can be molecularly absorbed onto the surface of the mesopores and, once solvent is removed, the drug is sterically trapped in this molecular form. In other words, the drug has no room to re-crystallize and can be delivered to the body as individual molecules, which has significantly higher dissolution and bioavailability performance.
Oral lipid based formulations
An oral lipid based formulation (LBF) is a bio-enabling formulation approach for poorly water soluble and highly lipophilic drugs. It utilizes lipids such as olive oil or sunflower oil, surfactants and co-solvents to solubilize the drug. In a conventional LBF the drug is fully solubilised in the formulation prior oral administration. This “circumvents” the dissolution of the drug in the gastro intestinal tract.
Paediatric formulation
The composition of a particular dosage form of a medicine for paediatric use.
Paediatric population
The International Conference on Harmonisation (ICH) subdivides the paediatric population in several age groups:
  • Newborns: 0 to 27 days
  • Infants: 28 days to 23 months
  • Children: 2 to 11 years
  • Adolescents 12 to 16/18 years
PBPK modeling
Physiologically-based pharmacokinetic models are complex mathematical models that consider absorption, distribution, metabolism and elimination of a drug. These processes are integrated on a mechanistic level using various information as physiology of the patients (e.g., organ size, enzyme expression and blood flow), the characteristics of the drug/formulation and the trial design. PBPK models can also be coupled with pharmacodynamic models to predict the drug effect in the patient.
Pharmacodynamics
Pharmacodynamics refers to the relationship between the concentration of drug at the site of action and the biochemical and physiological effect in the body, including the time course and intensity of therapeutic and adverse effects.
Pharmacokinetics
Pharmacokinetics describes how the body affects a drug after adminstration, involving mechanisms like absorption, distribution, metabolism and elimination.
Precipitation Inhibitor
Precipitation inhibitors sustain the drug in the supersaturated state to allow for sufficient absorption to take place. Most supersaturating formulations are combined with a precipitation inhibitor.
Public Engagement
Taking measures for promoting the action itself and its results to a multitude of audiences. The main aims are to reach out to society as a whole and some specific audiences and to demonstrate how EU funding contributes to tackling societal challenges.
Regulatory authorities
Medicine regulatory authorities are state or independent bodies that regulate the drug and medical devices development and production process in order to safeguard the health of the population. They do that by issuing and monitoring the compliance to guidlines for drug development,licensing, registration, manufacturing, marketing and labeling.They operate in a state, national or centralised manner.
S(M/N)EDDS
Self-emulsifying drug delivery systems (SEDDS) are isotropic mixtures of oils or lipids, surfactants, solvents and co-solvents and are typically used to formulate poorly water soluble drug compounds in order to improve their oral absorption. Depending on their composition these systems can self-emulsify in the gastro-intestinal tract after oral administration as droplets with sizes in the micro (SMEDDS) or nano range (SNEDDS).
Solid dispersion
One of the formulation approaches used for poorly soluble drugs. Originally it was defined as "a dispersion of one or more active ingredients in an inert carrier at the solid state, prepared by either the melting, the solvent or the melting solvent method" by Chiou and Riegelman in 1971.
Special patient populations
Special populations show differences in the physiology compared to healthy volunteers that are usually present in clinical trials. For example, differences can be due to maturation in paediatric patients, due to ageing processes in geriatric patients or due to diseases in patients with gastrointestinal diseases, renal impairment or liver cirrhosis. Consequently, drug product performance can be different in these special populations and requires further investigation.
Supersaturating Formulations
Supersaturating formulations are any formulation that generate supersaturated concentrations of API. Supersaturation refers to any concentration above the thermodynamic solubility, that is, the 'normal' solubility of a drug. Such an approach can improve the bioavailability of a poorly soluble drug due to artificially high concentrations of API in the GI tract.
Supersaturation
Supersaturation occurs if the concentration of a drug in solution exceeds its equilibrium solubility. Supersaturation of drug is an important consideration when designing the formulation of drug, as it can greatly affect the amount of drug absorbed in the human gastrointestinal tract.
Do you have questions regarding the explanation or want to receive some more details? Then do not hesitate to leave a comment in the section below.