Solid-State Properties and Solubility Studies of Novel Pharmaceutical Cocrystal of Itraconazole

Abstract

Objective: Pharmaceutical cocrystal is a promising method to improve the solubility of active pharmaceutical ingredients (APIs). Itraconazole (ITZ) is a BCS class II antifungal drug with poor aqueous solubility, therefore an attempt was made to improve the solubility of ITZ using cocrystallization technique. In this work, six novel pharmaceutical cocrystals of ITZ with various coformers, including 4-hydroxybenzoic acid (4HBA), trans-cinnamic acid (TCA), suberic acid (SUB), sebacic acid (SBC), 1-hydroxy-2-naphthoic acid (1H2N), and benzamide (BZD) were prepared.Methods: ITZ cocrystals was prepared by solvent evaporation process. The cocrystals produced were characterized using powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and fourier transform infrared (FTIR) spectroscopy. Solubility analysis was performed to evaluate the cocrystals.Results: PXRD and DSC analysis revealed that the pattern of all ITZ cocrystals was distinguishable from the individual compounds which indicates the formation of new phase. The solubility of ITZ and its cocrystals from highest to lowest after 24 h in 0.1 N HCl solution (pH 1.2) follows the order ITZ-TCA (1.97-fold), ITZ-SBC (1.09-fold), ITZ, ITZ-1H2N (0.58-fold) and ITZ-4HBA (0.46-fold).Conclusion: This study demonstrates that the selection of coformers has pronounced an impact on the physicochemical properties of ITZ. Based on this study, it can be concluded that cocrystallization offers a valuable way to improve the solubility of ITZ.

Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering

“…The crystallographic data and structure refinement details of KTZ−GTA, KTZ−PCA, KTZ−35DNB, and KTZ−26DHB are summarized in Table 1, and ortep diagrams have been provided in Figure S1, and the crystallographic data of KTZ−VNA has been provided in Table S2 due to the poor quality of the crystal structure. To date, crystal structures of KTZ salt with oxalate and cocrystals with some organic acids have already been reported [30][31][32][33][34]. The choice of CCFs was based on the following considerations: on the one hand, based on the supramolecular homosynthon and heterosynthon, considering the existence of imidazole and a piperazine ring in the KTZ structure and the high persistence of COOH/OH.…”

Micronized Eutectic Mixture of Fenofibric Acid-Saccharin Formation for Solubility and Dissolution Enhancement

“…FTIR analysis is used to identify the chemical group in the eutectic mixture by analyzing the molecular interactions at the specific wave number that appears in the spectrum [16]. Different compounds will produce a different infrared spectrum.…”

LIPOPHILICITY, AQUEOUS SOLUBILITY, AND DEGREE OF IONIZATION OF ATRACTYLODIN AND Β-Eudesmol, THE BIOACTIVE COMPOUNDS ISOLATED FROM ATRACTYLODES LANCEA

“…The aqueous solubility of the test compounds was determined by kinetic solubility assay, which is based on the detection of precipitation of the test compounds in aqueous solutions [19][20][21][22]. DMSO stock solution (10 mg/ml) of atractylodin or β-eudesmol was prepared by weighing 10 mg of each compound in 1 ml of DMSO.…”