Theoretical consideration of solubility by Hildebrand solubility approach

Pharmaceutical field is widely focusing on solubility parameter models to select solvent or non-solvent that can enhance solvency of drug. Solubility Parameter is very useful concept in understanding the mechanism of solvent and solvency behavior with their applications in pharmaceuticals to open the door of research having focus on theoretical considerations of solubility. Hildebrand and Hansen Solubility Parameter are frequently used to identify solvents.

Polymer Concentration Maximizes Encapsulation Efficiency in Electrohydrodynamic Mixing Nanoprecipitation

Encapsulation in self-assembled block copolymer (BCP) based nanoparticles (NPs) is a common approach to enhance hydrophobic drug solubility, and nanoprecipitation processes in particular can yield high encapsulation efficiency (EE). However, guiding principles for optimizing polymer, drug, and solvent selection are critically needed to facilitate rapid design of drug nanocarriers. Here, we evaluated the relationship between drug-polymer compatibility and concentration ratios on EE and nanocarrier size. Our studies employed a panel of four drugs with differing molecular structures (i.e., coumarin 6, dexamethasone, vorinostat/SAHA, and lutein) and two BCPs [poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) and poly(styrene)-b-poly(ethylene oxide) (PS-b-PEO)] synthesized using three nanoprecipitation processes [i.e., batch sonication, continuous flow flash nanoprecipitation (FNP), and electrohydrodynamic mixing-mediated nanoprecipitation (EM-NP)]. Continuous FNP and EM-NP processes demonstrated up to 50% higher EE than batch sonication methods, particularly for aliphatic compounds. Drug-polymer compatibilities were assessed using Hansen solubility parameters, Hansen interaction spheres, and Flory Huggins interaction parameters, but few correlations were EE observed. Although some Hansen solubility (i.e., hydrogen bonding and total) and Flory Huggins interaction parameters were predictive of drug-polymer preferences, no parameter was predictive of EE trends among drugs. Next, the relationship between polymer: drug molar ratio and EE was assessed using coumarin 6 as a model drug. As polymer:drug ratio increased from <1 to 3–6, EE approached a maximum (i.e., ∼51% for PCL BCPs vs. ∼44% PS BCPs) with Langmuir adsorption behavior. Langmuir behavior likely reflects a formation mechanism in which drug aggregate growth is controlled by BCP adsorption. These data suggest polymer:drug ratio is a better predictor of EE than solubility parameters and should serve as a first point of optimization.

Solubility of Cinnarizine in (Transcutol + Water) Mixtures: Determination, Hansen Solubility Parameters, Correlation, and Thermodynamics

Between 293.2 and 313.2 K and at 0.1 MPa, the solubility of the weak base, cinnarizine (CNZ) (3), in various {Transcutol-P (TP) (1) + water (2)} combinations is reported. The Hansen solubility parameters (HSP) of CNZ and various {(TP) (1) + water (2)} mixtures free of CNZ were also predicted using HSPiP software. Five distinct cosolvency-based mathematical models were used to link the experimentally determined solubility data of CNZ. The solubility of CNZ in mole fraction was increased with elevated temperature and TP mass fraction in {(TP) (1) + water (2)} combinations. The maximum solubility of CNZ in mole fraction was achieved in neat TP (5.83 × 10−2 at 313.2 K) followed by the minimum in neat water (3.91 × 10−8 at 293.2 K). The values of mean percent deviation (MPD) were estimated as 2.27%, 5.15%, 27.76%, 1.24% and 1.52% for the “Apelblat, van’t Hoff, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models”, respectively, indicating good correlations. The HSP value of CNZ was closed with that of neat TP, suggesting the maximum solubilization of CNZ in TP compared with neat water and other aqueous mixtures of TP and water. The outcomes of the apparent thermodynamic analysis revealed that CNZ dissolution was endothermic and entropy-driven in all of the {(TP) (1) + water (2)} systems investigated. For {(TP) (1) + water (2)} mixtures, the enthalpy-driven mechanism was determined to be the driven mechanism for CNZ solvation. TP has great potential for solubilizing the weak base, CNZ, in water, as demonstrated by these results.