While the so-called shake-flask method is considered the industry-standard for measuring accurate solubility, there actually exists no standardized protocol. Attempts by international working groups have been made in the past on consensus recommendations for improving data quality of solubility measurement (1), however, these are generally not well-integrated into company protocols.
In 2019 a consortium of Japanese universities and pharmaceutical companies reconfirmed the well known weakness of the industry-standard method (2). In an attempt to harmonize solubility measurement to lower inter-laboratory variance, more than 10-fold discrepancies in solubility in simple aqueous media were measured when using the proprietary protocols of each company.
So what is ‘true solubility’? The answer is, it does not exist. Every solubility value generated is a result of the method and protocol used, as well as the specific sources of error in the individual measurement event.
1. A. Avdeef et al., “Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality”, ADMET DMPK, vol. 4, no. 2, pp. 117–178, Jun. 2016.
2. A. Ono et al., “Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan”, ADMET DMPK, vol. 7, no. 3, pp. 183–195, Aug. 2019.
At The Solubility Company, we have developed a completely new way for accurate measurement of solubility. By minimizing potential sources of error and adding a high level of standardization for measurement hardware, software and protocols, accurate solubility can now be measured from microgram quantities of compound. We call it SPA® – talk to our experts.
Our Quakertown, PA and Helsinki, Finland laboratories have streamlined sample submission processes, shaving further time off the already impressive data turn around of The Solubility Company’s SPA® Platform.
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