What are the most notable challenges with measuring physiochemical properties and how is Sirius Analytical working to overcome these challenges?
Accuracy and understanding. We work hard to ensure that the physicochemical properties we measure, pKa, log P, solubility and dissolution rate are properly measured and that the results are accurate and correct. It was Sirius that established the use of 0.15M as the ionic strength for reporting pKa values, Sirius that introduced the Yasuda- Shedlovsky extrapolation method, and Sirius that introduced the concept of Chasers and non-Chasers that helps in understanding the nature of drug precipitation. Along with promoting excellence of measurement, we support education and training – helping people to understand how to use PhysChem properties in pharmaceutical science.
Could you outline features of the SiriusT3 Titrator?
The “3” in SiriusT3 stands for “third generation”. The previous two generations of instrument made accurate measurements, but the amount of sample required was sometimes too large. To allow pharmaceutical scientists to make measurements with very small sample quantities, SiriusT3 was designed to perform automated titrations under argon in just 1.5 mL of solution. Five probes are immersed in the solution throughout the titration, and the solution temperature is maintained by a Peltier system. Automation is the key to successful operation. Once the data has been collected, our Refinement software calculates results using procedures developed and enhanced by years of experience.
How do Sirius’ chemists and engineers work to meet customer demands for fast and accurate measurements?
pKa, log P and solubility are equilibrium properties, and it takes time for solutions to reach equilibrium. Even so, we strive to measure as fast as we can. It’s difficult to make measurements that are both “Fast” and “Accurate”, and we use automation to speed things up. With hundreds of readings required in each experiment, automation can better decide whether a pH is stable enough to be recorded and a UV signal is ready to read. A breakthrough was the development of our “Fast UV” method for pKa, where we cut the pH equilibration time by doing experiments in our “neutral linear buffer” solution.
How will your instrumentation and assay design software develop over the next few years?
As well as making instruments, we offer a measurement service and this has helped us keep abreast of changes in samples and user requirements. Hundreds of customers have sent samples, and the experience gained has helped us make advances in instrument technology. We see ourselves increasing our support for formulation scientists, who can take advantage of our CheqSol solubility and supersaturation studies. Another recent development was our GI Dissolution method, in which we study dissolution of a few milligrams of sample under conditions of changing pH to simulate what would happen to a drug after it’s been taken orally.
What features of Sirius Analytical’s products and services allow customers to easily review results and inspect the integrity of data?
The software includes a customizable reporting function from which the customer can export or generate a PDF of the selected information. The software that controls our instruments and calculates results from the data is based on 20 years of experience. It can read old data sets, even those collected on our first generation instruments. It records all the important details of an experiment so that it could be re-run at any time. Two copies of each data set are saved after each experiment, one for calculating a result and the other as raw data for archiving. Calibrations are traceable to primary standards, and imported into each experiment.