Solubility Modeling for Key Organic Compounds Used in Adavosertib (Anticancer API) Manufacturing

Area of Science:

• Pharmaceutical Manufacturing
• Physical Chemistry
• Computational Chemistry

Background:

• Solubility of organic compounds is critical for pharmaceutical manufacturing processes like reactions and crystallization.
• Predictive solubility modeling minimizes experimental work for new molecular entities (NMEs).

Purpose of the Study:

• To apply the Non-Random Two-Liquid Segment Activity Coefficient (NRTL-SAC) model for describing the solubility of six organic compounds involved in Adavosertib production.
• To utilize the NRTL-SAC model for estimating melting temperature and enthalpy of fusion, overcoming challenges in direct measurement.

Main Methods:

• Utilized the Non-Random Two-Liquid Segment Activity Coefficient (NRTL-SAC) model.
• Applied the model to six specific organic compounds related to Adavosertib (AZD1775) production.
• Estimated melting temperature and enthalpy of fusion using the NRTL-SAC model.

Main Results:

• The NRTL-SAC model successfully described the solubility of the six organic compounds.
• The model provided reliable estimations for melting temperature and enthalpy of fusion for these compounds.
• This approach circumvented difficulties associated with direct experimental measurements of thermal properties.

Conclusions:

• The NRTL-SAC model is a valuable tool for predicting solubility and thermal properties of organic compounds in pharmaceutical development.
• This predictive capability can streamline process development for new drugs like Adavosertib.
• The study demonstrates the utility of computational modeling in overcoming experimental limitations in pharmaceutical science.