In response to the realization that many products have failed due to formulation issues, pharmaceutical companies are putting much more emphasis on achieving optimal product formulations earlier in the development process. Using traditional manual experimental methods there is often only time to evaluate a limited number of formulations, sometimes throwing a drug development project into crisis mode.
To respond to this need, Symyx Technologies (Santa Clara, CA) has introduced the CORE(x) system of integrated Renaissance software, robotics, and analytical tools to enable a number of pharmaceutical sciences core workflows with high throughput, automated testing of drug candidates for formulation and preformulation solubility and stability assessment.
This integrated workflow increases formulation discovery productivity by 100x by making it possible to perform more experiments in the same amount of time required by traditional methods. A wide range of experiments can be run to gain an understanding of the product's solution behavior. An estimated annual throughput of 60,000 experiments or more can be achieved using this workflow. This translates to over 25 compounds per year that can be thoroughly evaluated.
Within preclinical development, the emphasis is on fully characterizing the new chemical entities coming out of lead optimization and turning those "leads" into "drugs". In general, development scientists identify crystallizable forms with salt selection and polymorph studies, determine solubility profiles, partition coefficients, pKa, determine the stability of the compounds and identify what decomposition products are formed, and perform initial formulation studies for excipient compatibility in order to improve solubility and stability.
Solubility profiles are important to understand the bioavailability of the drug as well as to develop the appropriate processing conditions for scale up and manufacturing. Scientists are interested in the solubility as a function of solvent composition, pH, and temperature. To develop a pharmaceutically acceptable drug, chemical and physical stabilities must be explored and addressed.
A nonoptimal formulation is often sufficient during the early development process but can often create major problems as clinical trials ensue. The earlier the active pharmaceutical is stabilized with an effective formulation, the more quickly it can move through the drug pipeline to the clinic. Many products have failed or been delayed due to formulation issues such as poor stability, loss of activity, and inability to meet specifications.
As the drug development pipeline increases, dosage form demands grow, and time pressures increase, the demand for additional preformulation and formulation resources makes it essential to automate the experimental process.
A workflow that generates and analyzes a large volume of data provides the level of understanding that makes it possible to move beyond intuition and guesswork in overcoming formulation problems. An integrated program of experiments can provide understanding of the product and its behavior in various environments and with various excipients.