Angelo Cortesi

Modelling solubility of solids in supercritical fluids using fusion properties

Abstract The modelling of solid solubilities in supercritical fluids is usually performed by means of thermodynamic models based on cubic equations of state together with the use of correlations for estimating the solid properties. However, it was shown in the literature, that the error in sublimation pressure, which is very low for high molecular weight compounds, is in many cases responsible for large deviations between experimental and calculated solubilities. In this work, the sublimation pressure of solids is estimated by using experimental fusion data and liquid–vapour equilibrium properties obtained from an equation of state (EOS). The results provided by this method are compared with those obtained using sublimation pressures from literature. It is shown that this method allows satisfactory solubility predictions when using a reliable EOS.

An experimental study of supercritical adsorption equilibria of salicylic acid on activated carbon

The supercritical desorption of solutes from porous media is a technology with a range of applications such as the treatment of contaminated soil and the regeneration of spent activated carbon. Although data in this field are scarce, previous studies have shown that supercritical adsorption equilibria have a significant role in defining supercritical desorption behaviour. The existing supercritical adsorption database is described and trends in the data are discussed. Experimental data for the system CO2 - salicylic acid - activated carbon are presented. A new apparatus incorporating dual high pressure syringe pumps and a high pressure UV cell was constructed to measure these data. Adsorption isotherms were measured at pressures between 90 and 250 bar and 308.1 K and 328.1 K. The influence of CO2 density and temperature on the adsorption equilibria is also studied. The adsorption data have been correlated with existing isotherm models.

Study of the solid state of carbamazepine after processing with gas anti-solvent technique

The purpose of this study was to investigate the influence of supercritical CO2 processing on the physico-chemical properties of carbamazepine, a poorly soluble drug. The gas anti-solvent (GAS) technique was used to precipitate the drug from three different solvents (acetone, ethylacetate and dichloromethane) to study how they would affect the final product. The samples were analysed before and after treatment by scanning electron microscopy analysis and laser granulometry for possible changes in the habitus of the crystals. In addition, the solid state of the samples was studied by means of X-ray powder diffraction, differential scanning calorimetry, diffuse reflectance Fourier-transform infrared spectroscopy and hot stage microscopy. Finally, the in vitro dissolution tests were carried out. The solid state analysis of both samples untreated and treated with CO2, showed that the applied method caused a transition from the starting form III to the form I as well as determined a dramatic change of crystal morphology, resulting in needle-shaped crystals, regardless of the chosen solvent. In order to identify which process was responsible for the above results, carbamazepine was further precipitated from the same three solvents by traditional evaporation method (RV-samples). On the basis of this cross-testing, the solvents were found to be responsible for the reorganisation into a different polymorphic form, and the potential of the GAS process to produce micronic needle shaped particles, with an enhanced dissolution rate compared to the RV-carbamazepine, was ascertained.

Supercritical fluids chromatography for impregnation optimization

Abstract Supercritical impregnation technique of polymeric matrix is going to have a very high interest in the pharmaceutical field. The possibility to obtain a final drug release product totally uncontaminated by organic solvents is a noticeable progress for the pharmaceutical factories. Two main steps are involved in the impregnation studies, the knowledge of the behavior of the drug/supercritical medium system, and the tedious and time consuming impregnation experiments for the choice of the conditions and for the choice of the proper matrix to be impregnated. In this work, an example of solubility study on anti inflammatory drug in supercritical carbon dioxide and in CO2/cosolvent mixtures, by a dynamic method is reported, moreover supercritical fluid (SF) chromatography technique is proposed as a tool which can give useful information on impregnation experiments in very short times.

Determination of partial molar volumes at infinite dilution using SFC technique

Abstract The use of supercritical-fluid chromatography for determining partial molar volumes of some substances (linear, cyclic and aromatic hydrocarbons, benzaldehyde) at infinite dilution in supercritical C02 is presented and discussed. Partial molar volumes at infinite dilution are obtained from the variation of the retention properties with the density of mobile phase at 313.15 K and in the pressure range from 80 to 280 bar.

Sorption of CO2 in biocompatible polymers: experimental data and qualitative interpretation

Abstract Sorption of CO2 (at 308.3 and 320.1 K in the pressure range of 0–120 bar) in different biocompatible polymers (ethyl-cellulose, carboxy-methyl-cellulose, and poly-vinyl-pyrrolidone) has been measured by a gravimetric method. The experimental data are qualitative, interpreted in terms of Gibbs free energy of mixing: in particular, the role of enthalpic and entropic effects are taken into account.

Preparation of Theophylline-Hydroxypropylmethylcellulose Matrices Using Supercritical Antisolvent Precipitation: A Preliminary Study

ABSTRACT Several controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

Determination of partial molar volumes at infinite dilution of alcohols and terpenes in supercritical carbon dioxide

Abstract The use of supercritical fluid chromatography for determining partial molar volumes of alcohols and terpenes at infinite dilution in supercritical CO2 is presented and discussed. Partial molar volumes at infinite dilution are obtained from the variation of the retention properties with the density of mobile phase at 313.15 K and in the pressure range from 85 to 280 bar.

Activity coefficients of hydrocarbons in polycarbonate by gas chromatography

Abstract Polycarbonates (PCs) are polyesters used for high-tech applications. For these applications many properties are needed. Gas chromatography can provide useful information about the thermodynamic properties of polymer systems for the determination of the parameters characterising polymer–solvent interactions. In this work, bisphenol A PC was studied by GLC: weight activity coefficients at infinite dilution and the Flory–Huggins parameter χ for paraffinic, cycloparaffinic and aromatic solvents have been determined. Two thermodynamic models, universal functional group activity coefficients (UNIFAC)-FV and GC-Flory equation of state (EOS), were applied to correlate the experimental data.

Correlation and prediction of infinite-dilution partial molar volumes of organic solutes in SC CO2 using the Peng-Robinson and PHCT equations of state and the LCVM EOS/GE model

An extensive infinite-dilution partial molar volume (PMV) data base of various liquid and solid solutes in supercritical carbon dioxide, including the very recent experimental partial molar volume data reported by Spicka et al. [B. Spicka, A. Cortesi, M. Fermeglia, I. Kikic, Determination of partial molar volumes at infinite dilution using SFC technique, J. Supercrit Fluids 7 (1994) 171] and Cortesi et al. [A. Cortesi, I. Kikic, B. Spicka, K. Magoulas, D. Tassios, Determination of partial molar volumes at infinite dilution of alcohols and terpenes in supercritical carbon dioxide, J. Supercrit. Fluids 9 (1996) 141] is used for a comprehensive study of the capabilities of three different thermodynamic models for the prediction of infinite-dilution partial molar volume data. The models are two equations of state, i.e. the well-known Peng-Robinson cubic EoS and the perturbed hard-chain theory (PHCT) EoS, and an EoS/GE model, the recently proposed LCVM group-contribution model. Correlation of the whole data base has been also considered with the Peng-Robinson EoS in order to determine the capability of a cubic equation of state to describe PMV data. Generally, all models were found to be semi-quantitative in the PMV prediction, especially in the range of the PMV minimum. Satisfactory prediction results are obtained using the Peng-Robinson EoS with interaction parameters from phase equilibrium data, and the fully predictive LCVM model. Both LCVM and the PHCT models tend to overpredict the PMV of n-alkanes in carbon dioxide in the high-pressure region, while PHCT always gives less satisfactory prediction results.