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

Obtaining data on the solubility of zolpidem, a sedative–hypnotic drug, in supercritical CO2 (scCO2) 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 scCO2 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 scCO2 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 scCO2–zolpidem and scCO2–ethanol–zolpidem systems, it was observed that the empirical models developed by Nejad and Keshmiri for the zolpidem–scCO2 system (AARD% ≈ 1.50 and Radj = 0.996) and by MST–Sauceau for the zolpidem–scCO2–ethanol system (AARD% = 3.51 and Radj = 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 scCO2–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 Radj = 0.999) in modeling zolpidem solubility in scCO2