The solubilities of trimethylolethane in butanol,methyl acetate,ethyl acetate as well as in mixed solvents of(methanol+ethyl acetate) and(ethanol+ethyl acetate) were measured with the gravimetric method in the tempera...The solubilities of trimethylolethane in butanol,methyl acetate,ethyl acetate as well as in mixed solvents of(methanol+ethyl acetate) and(ethanol+ethyl acetate) were measured with the gravimetric method in the temperature range from 283.15 K to 318.15 K under atmosphere pressure.The experiment results showed that the solubility of trimethylolethane increased with the temperature,or along with the concentration of methanol or ethanol in the solvents of(methanol+ethyl acetate) and(ethanol + ethyl acetate).In addition,the experiment values were correlated by the van't Hoff equation,Modi fied Apelblat Equation,λh Equation,CNIBS/R-K equation and Jouyban–Acree Model.The Modi fied Apelblat Equation provided the best fitting results of the solubility data of TME in the pure solvents while the CNIBS/R-K model showed the best estimation of the solubility in the binary solvent mixtures.Furthermore,the density functional theory(DFT) calculations showed that solubility in different solvents related to the strength of the interaction between the trimethylolethane and the solvent molecules.Finally,the standard molar enthalpy and molar entropy of trimethylolethane during the dissolving process was also calculated by Modi fied Apelblat equation in this work.展开更多
The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certa...The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.展开更多
In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method...In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.展开更多
Despite the potential advantages of amorphism-induced supersaturation,the merit of new amorphiza-tion formation methods on the properties of the amorphous drug including the stability of the amor-phous state,dissoluti...Despite the potential advantages of amorphism-induced supersaturation,the merit of new amorphiza-tion formation methods on the properties of the amorphous drug including the stability of the amor-phous state,dissolution/solubility,supersaturation,and"spring-parachute"process is still poorly understood,particularly for certain amorphous supersaturating drug delivery systems(aSDDS).The present work aimed to explore the detailed merit of current attractive amorphization manufacturing methods(i.g.,hot-melt extrusion(HME)technique)on the property improvement of aSDDS in form of amorphous solid dispersion microparticles by employing a model Bcs II drug nitrendipine and a polyvinylpyrrolidone-based model polymer copovidone.Many asDDS systems were developed by various methods,and their physicochemical properties were characterized by SEM,PXRD and DSC.HME-triggered amorphization induced superior supersaturation by the observation of the highest dissolution and solubility.HME induced the optimal supersaturation duration by the observed greatest extension of"spring-parachute"process(e.g,maximum AUCspring-parachute).HME technique is comparable with other techniques for the stabilization of amorphous state during storage.All aSDDS systems by HME and other methods showed improved long-term stability of the amorphous state in comparison to the pure amorphous drug.Fourier transformation infrared spectroscopy,Noyes-Whitney equation,nucleation theory and Gibbs free energy of transfer(△G)were used to analyze the underlying mechanisms.Mo-lecular mechanism studies indicated that HME caused a stronger crystallization inhibition effect in the asDDS systems than other methods,but molecular interaction is not a dominant mechanism for property enhancement caused by HME.For the mechanism associated with the polymer itself(PVPVA64),it could inhibit the drug recrystallization,solubilize the drug spontaneously and cause the improved molecular interactions in all aSDDS systems.This study provided a deep insight into detailed advantage of HME-triggered supersaturation/amorphization and facilitated the applications of the technique both in the field of particuology and in pharmaceutical industry.展开更多
基金Supported by the NSFC(21576206)the Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R46)
文摘The solubilities of trimethylolethane in butanol,methyl acetate,ethyl acetate as well as in mixed solvents of(methanol+ethyl acetate) and(ethanol+ethyl acetate) were measured with the gravimetric method in the temperature range from 283.15 K to 318.15 K under atmosphere pressure.The experiment results showed that the solubility of trimethylolethane increased with the temperature,or along with the concentration of methanol or ethanol in the solvents of(methanol+ethyl acetate) and(ethanol + ethyl acetate).In addition,the experiment values were correlated by the van't Hoff equation,Modi fied Apelblat Equation,λh Equation,CNIBS/R-K equation and Jouyban–Acree Model.The Modi fied Apelblat Equation provided the best fitting results of the solubility data of TME in the pure solvents while the CNIBS/R-K model showed the best estimation of the solubility in the binary solvent mixtures.Furthermore,the density functional theory(DFT) calculations showed that solubility in different solvents related to the strength of the interaction between the trimethylolethane and the solvent molecules.Finally,the standard molar enthalpy and molar entropy of trimethylolethane during the dissolving process was also calculated by Modi fied Apelblat equation in this work.
基金financially supported by the National Natural Science Foundation of China(Nos.21434008,21374054)National Basic Research Program of China(973 Program,No.2014CB932202)
文摘The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.
基金National Natural Science Foundation of China(Grant No.81172992)the National Basic Research Program of China(Grant No.973 Program 2009CB930300)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.
基金supported by National Natural Science Foundation of China(No.82172593 and 82204729)Science and Technology Development Program of Jjilin Province of China(No.20210101430JC,YDZJ202201ZYTS234 and YDZJ202201ZYTS223)+4 种基金China Postdoctoral Science Foundation(No.2015M571373)Science and Technology Development Program of jilin City in Jjilin Province of China(No.20200104067,201831739 and 201464053)Scientific Research Foundation of the Education Department of Jilin Province of China(No.JJKH20191072KJ and 2015-401)Doctoral Research Startup Fund Project of Jilin Medical University(No.JYBS2021002LK)the College Students'Innovation Project of Jilin Province(No.202013706026).
文摘Despite the potential advantages of amorphism-induced supersaturation,the merit of new amorphiza-tion formation methods on the properties of the amorphous drug including the stability of the amor-phous state,dissolution/solubility,supersaturation,and"spring-parachute"process is still poorly understood,particularly for certain amorphous supersaturating drug delivery systems(aSDDS).The present work aimed to explore the detailed merit of current attractive amorphization manufacturing methods(i.g.,hot-melt extrusion(HME)technique)on the property improvement of aSDDS in form of amorphous solid dispersion microparticles by employing a model Bcs II drug nitrendipine and a polyvinylpyrrolidone-based model polymer copovidone.Many asDDS systems were developed by various methods,and their physicochemical properties were characterized by SEM,PXRD and DSC.HME-triggered amorphization induced superior supersaturation by the observation of the highest dissolution and solubility.HME induced the optimal supersaturation duration by the observed greatest extension of"spring-parachute"process(e.g,maximum AUCspring-parachute).HME technique is comparable with other techniques for the stabilization of amorphous state during storage.All aSDDS systems by HME and other methods showed improved long-term stability of the amorphous state in comparison to the pure amorphous drug.Fourier transformation infrared spectroscopy,Noyes-Whitney equation,nucleation theory and Gibbs free energy of transfer(△G)were used to analyze the underlying mechanisms.Mo-lecular mechanism studies indicated that HME caused a stronger crystallization inhibition effect in the asDDS systems than other methods,but molecular interaction is not a dominant mechanism for property enhancement caused by HME.For the mechanism associated with the polymer itself(PVPVA64),it could inhibit the drug recrystallization,solubilize the drug spontaneously and cause the improved molecular interactions in all aSDDS systems.This study provided a deep insight into detailed advantage of HME-triggered supersaturation/amorphization and facilitated the applications of the technique both in the field of particuology and in pharmaceutical industry.
