Measurement and Modeling of Zolpidem Solubility in Supercritical Carbon Dioxide: Effect of Two Cosolvents

Abstract

Obtaining data on the solubility of zolpidem, a sedative−hypnotic drug, in supercritical CO 2 (scCO 2 ) is a crucial step in the development of an efficient supercritical process designed to formulate an effective drug delivery system for this medication. The current investigation entailed determining the solubility of this substance in scCO 2 across a range of temperatures (308.0, 318.0, 328.0, 338.0, and 348.0 K) and pressure values between 17 and 41 MPa. Furthermore, the research delved into assessing the impact of two cosolvents, DMSO and ethanol, on the supercritical solubility of this drug under the given conditions. The solubility of zolpidem in scCO 2 was within the mole fraction range of 1.19 × 10 −4 −3.23 × 10 −4 . However, when ethanol and DMSO were introduced, the solubilities were enhanced to the ranges of 3.09 × 10 −4 −22.13 × 10 −4 and 1.31 × 10 −4 −12.44 × 10 −4 , respectively. It was noted that the impact of ethanol is more substantial, leading to an approximately 4−5 times improvement in the supercritical solubility of zolpidem. Utilizing validated empirical models to correlate supercritical solubility data for both the scCO 2 −zolpidem and scCO 2 −ethanol−zolpidem systems, it was observed that the empirical models developed by Nejad and Keshmiri for the zolpidem−scCO 2 system (AARD% ≈ 1.50 and R adj = 0.996) and by MST−Sauceau for the zolpidem−scCO 2 −ethanol system (AARD% = 3.51 and R adj = 0.995) exhibited the highest levels of consistency between the predicted solubility values and the actual experimental data. Also, the supercritical solubility data of the scCO 2 −zolpidem binary system were evaluated by using the SRK and UNIQUAC models. It was observed that the SRK model demonstrated exceptional accuracy (AARD% = 1.53 and R adj = 0.999) in modeling zolpidem solubility in scCO 2 .