OPTIMIZATION OF DRUG SOLUBILITY USING ASPEN PLUS: ACETAMINOPHEN SOLUBILITY, A CASE STUDYAbstract
The optimization of aqueous and non-aqueous solubility of a drug or a drug-like molecule can be examined via the Aspen Plus simulation platform. Paracetamol (solute) will be taken as a case study. The following solvents were used in our dry (virtual) lab experiment: water, paracetamol (PARACTML), used as a solid solute, Di-Ethylene-Glycol (DEG), 1,2-Propanediol (PROPGLYC), and Poly-Ethylene-Glycol (PEG). A simplified flow sheet made of a single mixing tank where it has three feed streams, representing the solute, the water, and the set of organic solvents and one product stream where paracetamol is solubilized (liquid solution). Three different objective functions were used: Minimization of both the molar Gibbs free energy of mixing, ∆Gmix, and the molar Gibbs free energy of the mixture, Gmix, and maximization of the mass solubility of paracetamol in solution, expressed in g/L. The NRTL property method was used to analyze the solution properties. Using the molar Gibbs free energy, Gmix, as a criterion of solution thermodynamic stability, it was found that a binary non-aqueous mixture made of 14.64% paracetamol and 85.36 weight % PEG scored the top rank (i.e., lowest Gmix), the quinary mixture made of 5.06 water, 36.40 paracetamol, 27.74 DEG, 19.96 PROPGLYC, and 10.84 weight % PEG scored the second rank, and the binary aqueous mixture made of 29.56 weight % paracetamol scored the third rank. Finally, the pure solid crystal of paracetamol assumed the highest Gmix.