Centre for Drug Candidate Optimisation - Disciplines

Physicochemical Profiling

Assessing the physicochemical properties of a drug candidate in early discovery provides critical information regarding potential problems with in vivo absorption and bioavailability, disposition and product formulation. Physicochemical profiling has become an integral part of drug discovery leading to property optimisation and rank ordering for 'drug-like' characteristics.

Physicochemical profiling at the Centre is conducted in silico to provide prospective data on a structural series.  Once compounds have been synthesised, high throughput physicochemical screening only requires minimal quantities of material.

The Centre can provide:

• rapid and automated measurements of aqueous solubility under physiologically relevant conditions using either high throughput methods or equilibrium solubility measurements
• Log P/Log D determination using rapid chromatographic techniques or traditional 'shake-flask' methods
• computational estimates of solubility, pKa, Log P/Log D and polar surface areas, and other molecular surface properties related to membrane permeation.

The following studies can be conducted during later stages of development:

• assessment of impurity profiles
• short term solution and solid state stability under accelerated conditions
• solid state characterisation, including thermal analysis and hygroscopicity
• recrystallisation studies to identify potential polymorphic forms.

Salt selection and solid state characterisation

Rapid identification and selection of the optimal salt form for basic and acidic candidate drugs is a key development step in their early pre-clinical assessment.  The systems and methods at the Centre have been adapted to a small scale, and the salts selected for advancement are assessed for their physicochemical, biopharmaceutic, solid state and stability characteristics.

Compound Inventory

All compounds received by the Centre are entered into an inventory system maintained on a secure and confidential database. Security of compound identity and structure is ensured by limiting access to the database and restricting file access to read only.