For most of drugs to be effective, they should possess certain extent ability of permeating across at least one cellular membrane to get the intended targeted site. Especially for those oral dosage forms, a poor membrane permeability generally leads to a significant reducing in final efficacy. Similar to the permeability, partition coefficient can be used as the important parameter to predict the capacity of drug molecules transport into the epithelial cells from the gastrointestinal track, which are useful to forecast the potential efficacy, bioavailability and even the pharmacokinetic properties. Partition coefficient of a compound can be visually reflected by the lipophilicity which is usually introduced to describe a compound’s affinity to be in lipid-like environment.
Recognizing the fact that less than 10% of those drug candidates that enter clinical development receive the market access. Majority of drug failures are mainly ascribed to the unfavorable pharmacokinetic, ADME properties, toxicity and adverse side effects that are closely related to the undesirable permeability/partition coefficient properties of drug substances. In this case, a detailed knowing of the permeation behavior of a pharmaceutical compound plays an essential role in predicting the pharmacokinetics and rational drug design.
The permeability of a drug substance is affected by numerous factors such as the pH value of the surrounding liquid environment, and the hydrophilicity or lipophilicity of itself. Determination of the permeability coefficient for a compound is always characterized by highly complex and difficult. BOC Sciences has a team of highly trained workers to help you comprehensively determine the permeability of your compound. In general, there are mainly two types of techniques in our laboratory suitable for your testing needs:
As the standard method recommended by United States FDA guidelines, Caco-2 permeability assay is the most widely approach used for determining both the passive and active transport and the absorption of orally administered drugs. Through assessment of the tested compounds’ bidirectional permeability and transport rate of across a Caco-2 cell monolayer membrane, the in vivo absorption of drug substances across the gut wall can be well predicted.
Such methodology is established to simulate permeability across different membranes by creating a specific lipid charge. PAMPA can significantly reduce the expense and time of actual in-vitro studies through utilizing an artificial membrane. With this kind of simplified and efficient study approach, permeability of your compound can be tested with various membranes include:
Blood-Brain Barrier Permeability
The partition-coefficient or distribution-coefficient is used to describe how a solute is distributed between two immiscible solvents and logarithm of the ratio can be termed as log P and log D, respectively. Determination of the value of log P or log D leads to a deeply understanding of the compound’s hydrophobicity and membrane permeability, which have a significant effect on drug molecule screening and formulation design. Our experts can provide you with a suit of partition coefficients testing services related to water-to-organic solvent, blood-to-tissue, plasma-to-milk, and percentage of human intestinal absorption and the steady-state volume of distribution.
BOC Sciences offers a full analysis service for determining the permeability/partition coefficient according to your needs. Our experts have accumulated extensive knowledge and experience in experimental protocol design, process optimization and report writing. By utilizing a broad range of analytical techniques such as high throughput screening methods, fast ADMET profiling assays, and computational approaches, we can help our clients quickly identify the most valuable drug candidates in the very early development stage.