title: Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility.
abstract: Self-micro emulsifying drug delivery system (SMEDDS) is one of the methods to improve solubility and bioavailability of poorly soluble drug(s). The knowledge of the solubility of pharmaceuticals in pure lipidic solvents and solvent mixtures is crucial for designing the SMEDDS of poorly soluble drug substances. Since, experiments are very time consuming, a model, which allows for solubility predictions in solvent mixtures based on less experimental data is desirable for efficiency. Solvents employed were Labrafil® M1944CS and Labrasol® as lipidic solvents; Capryol-90®, Capryol-PGMC® and Tween®-80 as surfactants; Transcutol® and PEG-400 as co-solvents. Solubilities of both drugs were determined in single solvent systems at temperature (T) range of 283-333K. In present study, we investigated the applicability of the thermodynamic model to understand the solubility behavior of drugs in the lipiodic solvents. By using the Van't Hoff and general solubility theory, the thermodynamic functions like Gibbs free energy, enthalpy and entropy of solution, mixing and solvation for drug in single and mixed solvents were understood. The thermodynamic parameters were understood in the framework of drug-solvent interaction based on their chemical similarity and dissimilarity. Clotrimazole and Fluconazole were used as active ingredients whose solubility was measured in single solvent as a function of temperature and the data obtained were used to derive mathematical models which can predict solubility in multi-component solvent mixtures. Model dependent parameters for each drug were calculated at each temperature. The experimental solubility data of solute in mixed solvent system were measured experimentally and further correlated with the calculates values obtained from exponent model and log-linear model of Yalkowsky. The good correlation was observed between experimental solubility and predicted solubility.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 Dekalb Avenue, HS Bldg 612, Brooklyn, NY 11201, United States.
authors.forename: Shruti V
authors.initials: SV
authors.lastname: Patel
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 Dekalb Avenue, HS Bldg 612, Brooklyn, NY 11201, United States. Electronic address: Sarsvatkumar.Patel@liu.edu.
authors.forename: Sarsvatkumar
authors.initials: S
authors.lastname: Patel
mesh_terms: D003022:Clotrimazole / Q000737:chemistry; D015725:Fluconazole / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008055:Lipids; D012997:Solvents; D015725:Fluconazole; D003022:Clotrimazole
keywords: Activity coefficient; Clotrimazole; Co-solvents; Fluconazone; Lipidic solvents; Self-emulsifying drug delivery system; Surfactants; Thermodynamics; Van’t Hoff equation; Yalkowsky model