Determination Of Solubility Parameters Research Articles

Determination of Hansen solubility parameters of water-soluble proteins using UV–vis spectrophotometry

Determination of solubility parameters by dissolution tests are difficult for some valuable molecules, such as proteins, where the quantities available are small, UV–vis spectroscopy can determine dissolved concentrations of even small amounts of material, but accurate determination of dissolution is difficult in relatively poor solvents, due to difficulty with constructing a reliable calibration curve. In this work we report a new simple procedure to determine the relative dissolution of proteins in various solvents using UV vis spectroscopy for the determination of Hansen solubility parameters (HSP) of proteins. This method allows qualitative determination of the amounts of BSA dissolved in various solvents. The amounts of BSA dissolved in each solvent, can then be used to rank solvents as good or bad for HSP calculation purpose, which gives more reliable ranking than observation alone in dissolution tests. To be able to evaluate the HSP of any solid material, the solubility of the tested material in a range of solvents needs to be determined. Solvents are then scored as good or bad based on observations and from the known properties of those solvents, the HSP of the solute molecule in question can be calculated. Here, bovine serum albumin (BSA) was used as a model protein, but the procedure reported here can be applied to any soluble protein or other macromolecule with a clear UV/vis adsorption peak. This procedure requires the tested material to be highly soluble in water, therefore eliminating the need for the preparation of many standard solutions of BSA in different solvents. Only a set of standard solutions of protein in water is required. UV–vis spectroscopy was used to analyze the remaining solid resuspended in water after centrifugation of solutions of BSA dissolved in other solvents to separate any undissolved protein. The HSP of BSA obtained via this procedure was compared to values previously obtained for BSA using other methods. A very good agreement between the HSP obtained in this work with the that reported by Houen et al. which used amino acid analysis for the estimation of the solubility of BSA in various organic solvents.

Solubility and thermodynamic parameters of nicotinic acid in different solvents

Nicotinic acid is an important compound needed for the body to keep proper functioning and stay healthy. The determination of solubility parameters in different solvents can be useful for operations such as crystallization or encapsulation of nicotinic acid. In this study, we critically evaluated the solubility of nicotinic acid in nine solvents: water, methanol, ethanol, propanol, propan-2ol, butanol, acetone, ethyl acetone and dimethyl sulfoxide (DMSO). Solubility data are provided as mole fractions of solvent versus temperature. Results showed that DMSO afforded the highest nicotinic acid solubility, greater than the ideal solubility values. Thermodynamic parameters such as the activity coefficient, melting temperature and enthalpy of fusion were determined by differential scanning calorimetry. Non-predictive activity coefficient models were obtained to represent the experimental data through Margules, van Laar, Wilson, NRTL, and UNIQUAC equations. The van Laar, Wilson, and NRTL models showed broadly similar performance. The UNIQUAC model showed an optimum performance for six of the nine solvents.

Determination of solubility parameters and thermodynamic properties in hydrocarbon-solvent systems by gas chromatography

Gas chromatography used to calculate the specific retention volume of several hydrocarbons in different chromatographic liquid phases (Squalane, Carbowax-400, Carbowax-1500, Carbowax-4000, Amine-220, Dinonyl phthalate, Tributyl phosphate and Trixylenyl phosphate). Some thermodynamic parameters, such as enthalpy of sorption and Flory-Huggins parameters relating the interaction between liquid phases and solutes, were also calculated from the determined retention volumes. Liquid phase solubility parameters of Squalane, Carbowax-400, Carbowax-1500 and Carbowax-4000 at 80 ºC as well as the polar and apolar components were calculated too. A new model was proposed to correlate polar contribution to the solubility parameter of a liquid phase with the specific retention volume of a solute in this liquid phase.

Theoretical and Practical Approaches for Prediction of Drug–Polymer Miscibility and Solubility

Crystallization of drugs formulated in the amorphous form may lead to reduced apparent solubility, decreased rate of dissolution and bioavailability and compromise the physical integrity of the solid dosage form. The purpose of this work was to develop thermodynamic approaches, both practical and theoretical, that will yield a better understanding of which factors are most important for determining the ability of polymers to stabilize amorphous active pharmaceutical ingredients (API). Lattice based solution models were used to examine miscibility criteria in API-polymer blends. Different methods were used to estimate the Flory-Huggins interaction parameter for model API-polymer systems consisting of felodipine or nifedipine with poly(vinylpyrrolidone) (PVP). These were melting point depression and determination of solubility parameters using group contribution theory. The temperature and enthalpy of fusion of crystalline API alone and the fusion temperature of the API in the presence of the polymer were measured by differential scanning calorimetry. The resultant thermal data were used to estimate the reduced driving force for crystallization and the solubility of the API in the polymer. Flory-Huggins theory predicts that, for typical API-polymer systems, the entropy of mixing is always favorable and should be relatively constant. Due to the favorable entropy of mixing, miscibility can still be achieved in systems with a certain extent of unfavorable enthalpic interactions. For the model systems, interaction parameters derived from melting point depression were negative indicating that mixing was exothermic. Using these interaction parameters and Flory-Huggins theory, miscibility was predicted for all compositions, in agreement with experimental data. A model was developed to estimate the solubility of the API in the polymer. The estimated solubility of the model APIs in PVP is low suggesting that kinetic rather than thermodynamic stabilization plays a significant role in inhibiting crystallization. The thermodynamics of API-polymer systems can be modeled using solution based theories. Such models can contribute towards providing an understanding of the compatibility between API and polymer and the mechanisms of physical stabilization in such systems.