Solubility of Ketoconazole in Ethanol + Water Mixtures at Various Temperatures

Abstract

Ketoconazole is an important drug with low water solubility. Its low aqueous solubility could be increased using various methods such as by the addition of a pharmaceutical cosolvent. The solubility of ketoconazole in ethanol þ water mixtures at 293.2, 298.2, 303.2, and 308.2 K were determined, and the results showed that the addition of ethanol increased the solubility and the maximum value was obtained at 80% of ethanol. The generated data were mathematically represented using the Jouyban-Acree model within an acceptable accuracy.

Thermodynamic, Computational Solubility Parameters in Organic Solvents and In Silico GastroPlus Based Prediction of Ketoconazole

“…These are biocompatible and well-established skin permeation enhancers already explored in various topical and transdermal drug delivery. Moreover, several organic solvents (2-propanol, ethanol, PEG200, PEG400, and PEG600) have been investigated for improved solubility of KETO intended for pharmaceutical application. , Improved solubility in the explored permeation enhancer could be an ideal component for topical or transdermal delivery in the treatment of various dermal fungal infections. Therefore, the solubility of KETO in these permeation enhancers were envisaged and investigated for quantitative analysis followed by validation using thermodynamic and computational models.…”

“…The incidence of fungal infections occurred about 40 million in developing and under developing nations as per global estimates . Chemically, ketoconazole (KETO) is an azole type (±) ( cis -1-acetyl-4-[4-[2-(2,4-dichlorophenyl-2-(1H-imidazol-1ylmethyl)-1,3-dioxalon-4-yl]­methoxy]­phenyl]­piperazine) antifungal drug for local and systemic treatments . The empirical molecular formula and molecular weight of KETO are C 26 H 28 Cl 2 N 4 O 4 (Figure A) and 531.43 g mol –1 , respectively .…”

“…Hossin et al investigated the nail–drug interaction (affinity) using Hansen solubility parameters, which can assist formulation scientists to design a suitable carrier or solvent selection (DMSO, N -methyl pyrrolidone, ethanol, and ethylene glycol) for topical application with improved efficacy . Hashemzadeh and Jouyban studied the binary system of ethanol + water mixture for improved solubility of KETO at various temperatures using a Jouyban–Acree model of co-solvency . Moreover, authors reported that KETO exhibited the maximum mole fractional solubility (0.117) at 308.2 K when the mass fraction of ethanol in water was 0.8 .…”

Validation of UV Spectrophotometric Method for Quantifying Ketoconazole Encapsulated in Ethyl Cellulose Microspheres

“…Ketoconazole is a drug poorly soluble in water but soluble in some common solvents like ethanol and dichloromethane . Ethyl cellulose is soluble in alcohols, ketones, esters, aromatic hydrocarbons and chlorinated solvents .…”

Impact of azole drugs on energetics, kinetics, and ligand migration pathways of CO photo-dissociation in bacterial flavohemoglobins

“…Protein samples were prepared by diluting a freshly-melted aliquot of the protein stock with the sample buffer, 10 mM sodium phosphate and 10 mM KCl buffer, pH 7.5. For samples in the presence of ketoconazole and miconazole, the nal drug concentrations in the sample buffer were 8.5 mM for ketoconazole and 408 mM for miconazole 13 at 20 C. Low molar solubility of ketoconazole in aqueous solution at neutral pH, 1.4 Â 10 À5 , 12 restricted the amount of the drug used in this study. The concentration of miconazole was selected to have 99% of fHbs in the miconazole bound form as described below.…”