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

## TL;DR

This paper uses a solubility model to predict the behavior of organic compounds used in making an anticancer drug, reducing the need for extensive lab testing.

## Contribution

The study applies the NRTL-SAC model to predict solubility and thermodynamic properties of six compounds in Adavosertib manufacturing.

## Key findings

- The NRTL-SAC model accurately describes the solubility of six organic compounds used in Adavosertib production.
- The model estimates melting temperatures and enthalpy of fusion without direct experimental challenges.
- This approach minimizes the need for time-consuming and resource-intensive experimentation.

## Abstract

The solubility of
organic compounds plays an important role in
pharmaceutical manufacturing since key unit operations such as reactors,
crystallizers, and solvent extraction units all rely on successful
reagent and product dissolution. Consequently, predictive solubility
modeling is very useful when developing new pharmaceutical processes,
so as to minimize the experimentation required to understand the solubility
of new molecular entities (NMEs). The present paper has thus employed
the Non-Random Two-Liquid Segment Activity Coefficient (NRTL-SAC)
model to describe the solubility of six organic compounds used in
the production of an experimental anticancer drug, Adavosertib (specifically:
AZD1775 Adavosertib Maleate, AZD1775 Aniline Maleate, AZD1775 Nitropip,
AZD1775 Hydroxymethylsulfanyl, AZD1775 Bromopyridine.HBr, and AZD1775
Pyrimidine). The NRTL-SAC model has also been employed to estimate
the melting temperature and enthalpy of fusion of these compounds,
circumventing various difficulties arising in direct measurements
(e.g., endothermic/exothermic phenomena near the melting point).