Ionization

Gemini Profiler™

The Gemini Profiler™ is a semi-automated, state-of-the-art potentiometric analyzer for measuring measuring pKa.  The instrument uses the potentiometric titration method developed by Alex Avdeef (Pion's founder).  The Gemini Profiler™ advantages include:

• Determines pKa in the presence of some precipitation, since the instrument corrects for intrinsic solubility.
• The Gemini Profiler™ does not need to perform separate blank titrations.  The "ABC" electrode parameters can be determined in situ, at the same time that pKa values are determined.
• Any cosolvent can be used, including the water-miscible solvents polyethylene glycol, bile salts, and methylpyrrolidone.  It also can determine cosolvent pKa < 2 and pK_a > 12.
• Determines log P and log D of ionized compounds.
• Determines intrinsic solubility and solubility as a function of pH (1-13, increments of 0.1)

Drug Discovery
With as little as 100 micrograms of sample, the Gemini Profiler™ delivers a complete solubility-pH profile. This allows you to make solubility an integral part of your optimization program at earlier stages of drug discovery, by allowing you to experimentally "calibrate" your high-throughput solubility prediction calculations. The result is earlier prediction of oral absorption.  Determination of pKa can be accomplished separately or in conjunction with solubility measurement.

Drug Development
For the same effort as a manual single-pH solubility measurement, the Gemini Profiler™ determines the whole pH range, automatically. Not only aqueous solubilities, but also solubilities in DMSO, methanol and acetonitrile. Following guidelines consistent with the BioPharmaceutics Classification System,  dose predicting is made easier. Solubilities less than 5 ng/mL to 50 mg/mL are possible.  You will not want to do another shake-flask solubility determination. pKas of sparingly soluble compounds are easily determined using a cosolvent extrapolation method. Determination of multiple or overlapping pKas are not a problem for the Gemini Profiler™.