A pharmaceutical chemist is developing an oral formulation for Drug X
CHEMISTRY · Multi-part · AP · Chemistry · Properties of Substances and Mixtures · Properties of Substances and Mixtures
Problem
A pharmaceutical chemist is developing an oral formulation for Drug X, a neutral molecule with two carbonyl groups and an extended aromatic system. Simple computational metrics predict a logP (octanol/water partition coefficient) of 4.2, suggesting poor aqueous solubility. Surprisingly, experimental measurements show Drug X dissolves in water up to 6 mg·mL⁻¹ at 25 °C when co-formulated with 30 % (v/v) polyethylene glycol 400 (PEG-400). The chemist must reconcile this discrepancy.
(a) Briefly describe why a high logP value usually correlates with low aqueous solubility.
(b) Explain how specific interactions between Drug X and PEG-400 can enhance the apparent solubility of Drug X in the aqueous formulation.
(c) Discuss why simply increasing temperature might not achieve the same solubility enhancement observed with PEG-400, despite the general effect of temperature on solubility.
(d) The chemist considers replacing PEG-400 with glycerol. Predict whether glycerol would be more, less, or equally effective at solubilizing Drug X and defend your prediction based on intermolecular forces and molecular structure.