Solubilizing excipients on the thermal properties of flavonoids Drug Effects
|Course||Physical and chemical|
|Keywords||silybin quercetin PVP K30 PVA hydrogel sodium cholate DSC heat capacity thermal dehydration kinetics|
Flavonoids, such as silybin and quercetin, are polar in structure, but poorly soluble in water in nature. This hydrophobic property limits their solubility, release rate in water and bioavalibility in medicine application. To improve their medicine efficience, a variety of methods in pharmaceutics have been developed, among them including solid dispersion method, inclusion complex method, and liposome and hydrogel carrier methods. In pharmaceutical technique, the mixing behaviour of drug and their additives directly impact the physical-chemical properties and the medicine efficience. Therefore, it is very important to study the physical-chemical properties of the mixtures of drug + additives.The solubility, solid release rate in water, and the phase equilibrium state of drugs are mainly determined by their thermochemical properties. Therefore, thermodynamic property is an essential data to evaluate the medicine efficience of drugs. In this article, we focus our attention to some binary systems composed of flavonoids (silybin, quercetin) and their additives (Poly(vinylpyrrolidone) (PVP), Polyvinyl alcohol (PVA) and sodium cholate, etc.). Some basic thermodynamic properties, such as heat capacity and phase transition state, and their changes with temperature and compositions are studied. This work includes four parts.1. In chapter 2, we report the study on the binary system of (quercetin + PVP K30). Solid dispersions and mixtures of quercetin and PVP K30 are studied by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and heat capacity (Cp) measurements. A solid dispersion is found in the region of w1 < 0.5, and a solid mixture is found in the region of w1 > 0.5, where w1 is the mass fraction of quercetin. The Cp data is correlated to temperature T by a polynomial equation, and changes in enthalpy and entropy were calculated from Cp. The work in this chapter has been published in J.Chem.Eng.Data, 2010, 5856.2. In chapter 3, we report the study on the binary mixtures of (silybin + PVP K30). The heat capacity Cp of the binary system has been measured by DSC and FT-IR spectroscopy. By analyzing the curves of (dCp/dT) against temperature T, some apparent points, a maxima point and a minima point, to characterize the Cp curve were obtained. The maxima point in the region of w1< 0.4 is a character of amorphous solid state of PVP, where w1 is the mass fraction of silybin. In this region, silybin is dispersed into the amorphous solid of PVP. The minima point in the w1> 0.4 region is a character of crystalline silybin. In this region, a mixture of crystalline silybin with an amorphous solid dispersion is observed. The Cp data is correlated to temperature T by a polynomial equation, and the changes in enthalpy and entropy were calculated from Cp. The work in this chapter has been published in Thermochim Acta, 2011, 99.3. In chapter 4, we report the work on the binary system of (silybin + sodium cholate). The heat capacity of this binary system has been measured by DSC in the temperature range from 298.15 to 373.15 K. X-ray diffraction and FT-IR spectroscopy were used to determine the solid mixing behaviour. Our result indicates that, the binary system of silybin and sodium cholate is a mixture of two micro-crystaline components. The excess heat capacities of this binary system were correlated by the Redlich-Kister equation. Thermodynamic functions of the entropy and enthalpy were calculated in the experimental temperature range.4. Hydrogels can be used as a drug carrier. Its application in biology and medicine depends seriously upon its water content. By a repeated freezing and thawing method, the hydrogels of PVA blended with PVP were prepared. The thermal dehydration kinetics of this gel was investigated by DSC measurement, which is significantly dependent on the PVP content. The kinetic parameters of the dehydration process of PVA+PVP gel were obtained by the Kissinger method, by the Flynn-Wall-Ozawa method, and by a method to fit the DSC data with some definite kinetic equations, respectively. The effect of PVP content on the dehydration of PVA hydrogel can be found from the kinetic parameters.