Luis Antonio Estévez

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.

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.

Mebeverine hydrochloride is an important drug to treat irritable bowel syndrome. The solubility of this drug in supercritical carbon dioxide was measured at temperatures from 35 to 65 °C and pressures from 12 to 30 MPa. Results were between 2.16 and 30.2 ppm by mole. The data were correlated with density‐based models (K‐J, MST, Chrastil, Garlapati and Madras, Bartle et al., and Sparks et al.) and equations of state (Peng‐Robinson, Soave, and Estévez et al. models). The mean relative deviation and corrected correlation coefficient were used to assess the goodness of the models. Based on all ten models, Sparks et al. performed best according to average absolute relative deviation (5.64 %), and Bartle et al. was the best according to R_adj (0.997). However, this contribution's main merit is the reported experimental data.

In-situ Fourier transform infrared spectroscopy measurements were obtained by using an innovative equipment to study the heterogeneous reaction between a hydrolyzed porous methylsilsesquioxane film and hexamethyldisilazane (HMDS) dissolved in CO₂ at supercritical conditions. Gas and solid infrared signatures were separated to obtain kinetic information of the heterogeneous reaction. A two-step reaction mechanism was observed: a fast first step controlled by kinetics and a second step controlled by the diffusion of the HMDS inside the porous material. Infrared information was used to derive a rate law expression of the silylation reaction between HMDS and Si-OH. A first order of reaction relative to the concentration of hydrophilic sites was observed with activation energy of 51.85 ± 1.25 kJ/mol.

Surface functionalization of hydrolyzed methyl-silsesquioxane films were performed by treatment of samples with trimethylchlorosilane (TMCS) and methyltrichlorosilane (MTCS) dissolved in supercritical carbon dioxide. Films thicknesses modifications, pore size distributions, hydrophobicity, dielectric constants, and chemical reaction analyses were performed by ellipsometry, ellipsometric porosimetry, goniometry, electrical measurements, and Fourier transform infrared spectroscopy, respectively. As results, the properties of the functionalized films were able to be modified in function of reaction conditions (concentration, temperature, and/or pressure). Layers thicker than a monolayer were deposited by both TMCS and MTCS, and a tradeoff between the surface functionalization and layer thickness for both chemicals was observed. The results led to the conclusion that a combination of reagents or processing steps could be used for surface properties tuning.