The use of parallel screening to overcome bioavailability issues

The clock on patent expiry starts ticking long before the regulatory authorities grant marketing approval. Therefore, any strategy that can accelerate a drug development pathway to market is likely to improve its commercial impact … should it be approved. However, the identification of a suitable formulation for orally delivered small molecule drugs is becoming ever more challenging. Roughly two thirds of all oral new chemical entities in the development pipeline can be classified as poorly soluble, with permeability issues also affecting a fifth of drugs. As a result, absorption may be both insufficient and inconsistent when such drugs are administered along with or without food.

The traditional method for categorising molecules according to their solubility and permeability properties is the Biopharmaceutics Classification System (BCS). This categorises a drug into one of four classes and represents a good, broad guideline for identifying a successful formulation; however, it is not definitive for those drugs that fall into Class II, as these have problems with solubility, for which the solutions are rarely straightforward. The classification system therefore has a limit to its usefulness when formulating drugs in this quadrant.

More recently, an alternative, the Developability Classification System (DCS), has been introduced. This is more effective at helping to identify formulation alternatives by splitting the problematic Class II quadrant into two subgroups. If the drug has a limited dissolution rate, it will fall into Class IIa; whereas if the issue is limited solubility, then it will be defined as Class IIb. The boundary between the two is represented by the solubility limited absorbable dose (SLAD), which is the dose above which absorption is limited by solubility. Above the SLAD, merely making smaller particles to speed up dissolution will not suffice.