| β-Arbutin is a kind of natural active substance widely existing in plants and fruits,with whitening and freckle removal,antibacterial and anti-inflammatory effects,and is a widely used cosmetic additive and drug.At present,β-arbutin has three crystal types:anhydrousβ-arbutin,hemihydrateβ-arbutin and monohydrateβ-arbutin.Because different crystal forms of drugs can seriously affect their physical and chemical properties,clinical therapeutic effects,toxic and side effects and drug quality,it is one of the important research contents in the field of pharmaceutical research and development.In actual industrial production,the crystallization process,operation parameters and crystallization solvent adopted by different crystal types of the same drug will also be different,but this requires a large number of multivariate solid-liquid equilibria,i.e.dissolution equilibrium or solubility data as the basis.Therefore,the aim of this paper is to systematically determine the multivariate solid-liquid equilibrium data ofβ-arbutin in different solvent systems,and identify the crystal type ofβ-arbutin in the selected solvent system,so as to provide data guidance for the crystallization separation ofβ-arbutin and crystal drug research in practical industrial production.In this paper,the dissolution equilibrium data ofβ-arbutin in 12 pure solvents such as water,methanol,ethanol,n-propanol,isopropanol,sec-butanol,n-pentanol,acetone,acetonitrile,ethyl acetate,dichloromethane and 1,4-dioxane and 4 binary mixed solvent systems of water+acetone,water+isopropanol,methanol+acetonitrile and methanol+ethyl acetate were determined by static weighing method,and the crystal transformation of equilibrium solid phase was analyzed by powder X-ray diffraction and differential scanning calorimetry/thermogravimetry.The results showed thatβ-arbutin was transformed from anhydrousβ-arbutin to monohydrousβ-arbutin in pure water,water+acetone and water+isopropanol.In all solvent systems,the solubility ofβ-arbutin increased with increasing temperature.Under the same conditions,the solubility ofβ-arbutin in pure solvents was ranked as follows:dichloromethane<acetonitrile≈ethyl acetate<n-pentanol<acetone≈sec-butanol<isopropanol≈n-propanol<ethanol<1,4-dioxane<water<methanol.The solubility ofβ-arbutin in pure solvents is affected by solvent polarity,hydrogen bond,cohesive energy density and other factors.The synergistic solvation effect ofβ-arbutin was observed in water+acetone,water+isopropanol and methanol+acetonitrile,and the solvent compositions with maximum solubility were 0.700（water+acetone）,0.800（water+isopropanol）and 0.900（methanol+acetonitrile）,respectively.The reason is thatβ-arbutin formed strong intramolecular hydrogen bonds in the three binary solvents.In addition,the solvent effects ofβ-arbutin in the solvent system were comprehensively analyzed by solubility parameters.Finally,the modified Apelblat model,Yaws model,Machatha model,Jouyban-Acree model,Apelblat-Jouyban-Acree model and Apelblat-Machatha model were used to correlate the solubility data ofβ-arbutin.The results showed that the maximum values of ARD and RMSD of fitting pure solvent models were not more than 2.304×10-3 and 4.210×10-6,respectively,and the maximum values of ARD and RMSD of fitting binary mixed solvent models are not more than 3.746×10-1 and 1.095×10-2,respectively.It shows that all the thermodynamic models have achieved good fitting effect. |
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