Seyed Ali Sajadian

This study investigated the solubility of chlordiazepoxide in supercritical carbon dioxide (SCCO₂) at pressures ranging from 12 to 30 (MPa) and temperatures ranging from 308 to 338 (K). The measured solubilities ranged from 19.8 to 576 parts per million (ppm), or mole fractions of 0.0198 × 10⁻³ to 0.576 × 10⁻³. We used two equations of state (SRK and ECM-PR), enlarged liquid models, and semi-empirical analysis to assess the experimental data. Applying these models to the experimental solubility data of the chlordiazepoxide-SCCO₂ system revealed that Chrastil’s empirical models best aligned with the two sets of data. An important step in understanding the system’s behavior was applying the SRK and UNIQUAC models to the drug’s solubility data. Density-dependent empirical models, particularly the Chrastil correlation (AARD% = 5.30, R² = 0.996) and the UNIQUAC model (AARD% = 6.12), provided the highest predictive accuracy for chlordiazepoxide solubility in SCCO₂. In contrast, cubic EoS models (SRK and ECM-PR) exhibited significant deviations, with AARD% values approaching 20%, suggesting their limited reliability for this system. The UNIQUAC model indicated excellent accuracy, with AARD% of 6.12 and R² of 0.981 in correlating solubility data of this binary system.

Particle size reduction makes drugs more soluble and bioavailable in the body. Researchers are increasingly interested in supercritical fluid processes for the production of micro- and nanoparticles in pharmaceuticals. In this research, gas anti-solvent (GAS), polyvinyl pyrrolidone polymer (PVP), and dimethyl sulfoxide (DMSO) solvent processes were used for the first time to produce aripiprazole (antipsychotic drug) nanoparticles. This specific combination has not been previously reported for aripiprazole and represents the main novelty of the study. The effects of different operating conditions were evaluated using a Box-Behenken design, which also sought to highlight the optimal combinations of conditions to obtain the smallest particle size. The effects of temperature (308, 318, and 328 K), pressure (10, 13, and 16 MPa), and APZ/PVP ratio (1, 5, and 9 w/w) on particle size were investigated. The optimum values of temperature, pressure, and APZ/PVP ratio were 312 K, 16 MPa, and 1w/w, respectively, which resulted in the minimum particle size. FTIR, FESEM, DLS, XRD, DSC, and dissolution rate tests were used to investigate changes in physical - chemical properties. Good results were obtained by reducing the particle size from 104.6 ± 30.1 μm to 389.6 ± 24.2 nm at optimum condition.

This study reports, for the first time, the solubility investigation of yellow 23 in supercritical carbon dioxide over a pressure range of 12–30 MPa and a temperature range of 313–343 K.

The solubility of nilotinib hydrochloride monohydrate in supercritical CO₂ was measured at four temperatures between 338 K and 308 K, and seven pressures between 12 MPa and 30 MPa, using ethanol as a cosolvent. Both semi-empirical and empirical approaches were employed to analyze the experimental data. In the ternary systems studied, the solubility values (mole basis) for nilotinib hydrochloride monohydrate were between 1.08 × 10^− 5 and 4.15 × 10^− 4 (10.8 to 415 PPM). The results indicated a significant increase in solubility with the incorporation of ethanol. The peak solubility of nilotinib hydrochloride monohydrate was recorded in the ternary system at 338 K and 12 MPa, which was approximately 10.8 times its solubility in supercritical carbon dioxide alone under identical conditions. The best fit for the data, as measured by the average absolute relative deviation percentage (AARD%), was achieved using the methods proposed by MST.

Supercritical fluid-based methods have been receiving increasing popularity in the production of pharmaceutical nanoparticles due to their ability to control the size and distribution of the particles and offer high purity products. The gas anti-solvent method is one of the methods in which a supercritical fluid serves as an anti-solvent. The aim of this work is to develop pazopanib hydrochloride nanoparticles as an anti-cancer agent by the supercritical GAS method. For this purpose, nanoparticles were produced at different temperatures (313, 323 and 333 K), pressures (10, 13 and 16 MPa), and initial solute concentrations (12, 22 and 32 mg ml⁻¹) employing the Box–Behnken design. The results showed that pressure had the most significant effect on the particle size. The average initial particle size of unprocessed pazopanib hydrochloride was about 37.5 ± 8.7 μm. The optimum process parameter values were determined to obtain the smallest particle size using the BBD method. The parameters were optimized at 320 K, 16 MPa, and 12.6 mg ml⁻¹. The average particle size was 311.1 nm, close to the predicted value of 302.3 nm. FTIR analysis indicated that the chemical structure remained unaltered. Furthermore, DSC and XRD results confirmed the reduction in particle size.