Determination and prediction of solubility, dissolution, permeability and human absorption is Pion’s core business. We screen and analyze pharmaceutical compounds using instrumentation, software and laboratory services.
Meeting the Challenge. Typically, a large pharmaceutical company will test over 3,000,000 molecules for activity. While about 30,000 "hits" may be discovered in a year, only about 30 candidate molecules reach the development stage. Finally only 3 molecules enter the market as drugs, and rarely are these "blockbusters". More often than not, only one molecule reaches consumers.
Drugability - Getting The Job Done. Active compounds often are rejected due to poor oral absorption pharmacokinetics: while they may perform well in a test tube, in the body they just can’t reach their target sites. For example, the molecule may be just too insoluble in water, and like "brick dust" it is eliminated before it has a chance to interact. In order to reach a site of therapeutic action, a molecule has to traverse many barriers. These barriers are formed by cell membranes, composed of oily phospholipid bilayers, which block the passage of charged or hydrophilic molecules. If a molecule is highly charged, it will be highly soluble but then it will not pass these oily barriers. Other effects, such as metabolism and efflux will also limit absorption.
The Need for Better Prediction. Many candidate molecules fail because they cannot cross the phospholipid bilayer to reach their intended target. Laboratory test animals usually are not used during early screening for absorption efficiency. Although epithelial cell cultures such as Caco-2 are often used for this purpose, the tests are costly and require a licensing fee. There are much more effective approaches appropriate for early screening; absorption properties can be assessed by measuring the model-membrane bilayer permeability coefficient, the aqueous solubility and extent of retention by the membrane. This is often referred to as the acronym PSR (permeability-solubility-retention).
For ionizable molecules, the PSR parameters are dependent upon pH. At a given pH, the PSR parameters indicate the charge state of a drug molecule and its solubility in water and membranes, which predict in vivo absorption into the circulatory system. PSR profiles are used to prioritize molecules for further study and to reject some molecules altogether.
Solutions. Pion offers a range of instruments and analytical services that improve lead generation, optimization and selection. All our solutions include API-sparing techniques designed to measure and predict the critical physicochemical properties of target molecules.