Abstract
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.
Highlights
Cinnarizine (CNZ) (Figure 1, IUPAC name: 1-benzhydryl-4-[(E)-3-phenylprop-2enyl]piperazine, CAS number: 298-57-7, PubChem CID: 1547484, molecular formula: C26H28N2, and molar mass: 368.50 g mol−1) appears as a white crystalline powder [1,2]
Between 293.2 and 313.2 K and atmospheric pressure, Table 1 lists the solubility values of CNZ in mole fraction (3) in binary {TP (1) + water (2)} combinations, including neat TP and neat water
The mole fraction solubility of CNZ in water was reported to be 6.63 × 10−8, 7.71 × 10−8, and 9.35 × 10−8 at 298.3 K, 303.0 K, and 307.8 K, respectively [1]
Summary
Cinnarizine (CNZ) (Figure 1, IUPAC name: 1-benzhydryl-4-[(E)-3-phenylprop-2enyl]piperazine, CAS number: 298-57-7, PubChem CID: 1547484, molecular formula: C26H28N2, and molar mass: 368.50 g mol−1) appears as a white crystalline powder [1,2]. The biopharmaceutical classification system (BCS) classifies it as a BCS class II drug, meaning it has poor aqueous solubility and high permeability [1,4] It is a weak base, which is practically insoluble in water with a high partition coefficient value (log P = 5.8) [5]. It is used as a potential solubilizer/cosolvent in the preparation of various lipid-based drug delivery systems [2,9,17] It has been studied as a potential solubilizer in the solubility enhancement of various poorly soluble drugs, including sunitinib malate, flufenamic acid, sinapic acid, apremilast, ketokonazole, and sulphadiazine [18,19,20,21,22,23]. It was selected as a cosolvent in this study
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