A selection of 22 low-melting polymers was thermally and rheologically evaluated to be used as hot-melt adhesives in mixed-substrate joining samples. The choice of polymers was based on the published melting point. It...A selection of 22 low-melting polymers was thermally and rheologically evaluated to be used as hot-melt adhesives in mixed-substrate joining samples. The choice of polymers was based on the published melting point. It was required to include a broad variety of different polymers backbones to study the influence of the different polymers comprehensively. A tool-box of widely applicable tests was developed to judge if a thermoplastic polymer is suitable for a hot-melt adhesive application. Melting temperature (onset, peak and offset temperature) and melting enthalpy were determined using standardized methods. Rheological methods were used to characterize the shear rate dependence and the flow behavior at the application temperature. The wetting behavior of the polymers was evaluated with contact angle measurements. The adhesive strength of the most promising candidates was analyzed using the Lumi Frac-adhesion method including the failure pattern.展开更多
Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to inv...Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.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
In this study, a novel bio-based thermosetting system has been developed from epoxy resin （EP）, with rosin-sourced anhydrides （maleopimaric acid, RAM） as curing agent and imidazole type latent catalyst （two amino...In this study, a novel bio-based thermosetting system has been developed from epoxy resin （EP）, with rosin-sourced anhydrides （maleopimaric acid, RAM） as curing agent and imidazole type latent catalyst （two amino imidazole salt complex, IMA）, to be used as matrix for hot-melt prepreg curing at mid-temperature. For comparison, the epoxy resin system with petroleum sourced hardener methylhexahydrophthalicanhydride （MHHPA） was also examined. The curing behaviour and mechanism were investigated by non-isothermal differential scanning calorimeter （DSC） analysis and Fourier transform infrared （FTIR） spectra. The results showed that the curing course of bio-based epoxy resin system containing RAM included two stages, which were the reaction between the free carboxyl group of RAM and oxirane ring under the acceleration of IMA, and the main reaction attributed to the reaction between anhydride and oxirane. According to Kissinger method, the reaction activation energy （E,） of two stages were 68.9 and 86.5kJmo1-1, respectively. The Eo of EP/MHHPA and EP/IMA resin system were 81.04 and 77.9kJmol-I. The processing property of EP/RAM/IMA system, i.e. the relationship between viscosity-temperature-time, was characterized by cone-plate viscometer aim to decide the processing parameter ofprepreg preparation. The effect of RAM content on mechanical performance and dynamic mechanical property was investigated. Noteworthily, compared with the laminates with EP/MHHPA as matrix, the laminates with RAM as hardeners achieved a 44%, 73% and 70℃ increase in bending strength, bending modulus and the glass transition temperature, respectively, due to the bulky hydrogenated phenanthrene ring structure incorporated into the cross-linking networks. When the fiber volume fraction reached 47%, the mechanical property of the laminates prepared with hot melt prepreg was superior or comparable to that of composites with pure petroleum sourced matrix. RAM as cross-linking agent of epoxy resin holds a great potential to satisfy the requirement of composites such as structure and secondary structure parts preparation.展开更多
The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion(HME).Carbamazepine(CBZ)was selected as model drug and combinations of Kollidon VA64(VA64),Soluplus...The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion(HME).Carbamazepine(CBZ)was selected as model drug and combinations of Kollidon VA64(VA64),Soluplus(SOL)and Eudragit EPO(EPO)were utilized as carriers.Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters,differential scanning calorimetry(DSC),hot stage microscopy and thermogravimetric analysis.Physicochemical properties of solid dispersions were determined by DSC,X-ray diffraction,fourier transform infrared spectroscopy,dissolution and accelerated stability testing.The results show that drug-polymer miscibility at temperatures below the melting point(Tm)of CBZ was improved by combining EPO with VA64 or SOL.With 30%drug loading in a solid dispersion in SOL:EPO(1:1,w/w),CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form.The dissolution rate of the solid dispersion was significantly increased(approximately 90%within 5 min)compared to either the pure drug(approximately 85%within 60 min)or the corresponding physical mixture(approximately 80%within 60 min)before and after storage.The solid dispersion in SOL:EPO(1:1,w/w)was relatively stable at 401C/75%RH under CBZ tablet packaging conditions for at least 3 months.In conclusion,polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.展开更多
文摘A selection of 22 low-melting polymers was thermally and rheologically evaluated to be used as hot-melt adhesives in mixed-substrate joining samples. The choice of polymers was based on the published melting point. It was required to include a broad variety of different polymers backbones to study the influence of the different polymers comprehensively. A tool-box of widely applicable tests was developed to judge if a thermoplastic polymer is suitable for a hot-melt adhesive application. Melting temperature (onset, peak and offset temperature) and melting enthalpy were determined using standardized methods. Rheological methods were used to characterize the shear rate dependence and the flow behavior at the application temperature. The wetting behavior of the polymers was evaluated with contact angle measurements. The adhesive strength of the most promising candidates was analyzed using the Lumi Frac-adhesion method including the failure pattern.
基金supported by the National Natural Science Foundation of China(No.81402858)the Liaoning Natural Science Foundation(No.2015020736)Shenyang Pharmaceutical University Long-term Training Fund(No.ZCJJ2014406)
文摘Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.
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.
基金supported by the China-EU co-funded project ECO-COMPASS(Grant No.MJ2015-HG-103)
文摘In this study, a novel bio-based thermosetting system has been developed from epoxy resin （EP）, with rosin-sourced anhydrides （maleopimaric acid, RAM） as curing agent and imidazole type latent catalyst （two amino imidazole salt complex, IMA）, to be used as matrix for hot-melt prepreg curing at mid-temperature. For comparison, the epoxy resin system with petroleum sourced hardener methylhexahydrophthalicanhydride （MHHPA） was also examined. The curing behaviour and mechanism were investigated by non-isothermal differential scanning calorimeter （DSC） analysis and Fourier transform infrared （FTIR） spectra. The results showed that the curing course of bio-based epoxy resin system containing RAM included two stages, which were the reaction between the free carboxyl group of RAM and oxirane ring under the acceleration of IMA, and the main reaction attributed to the reaction between anhydride and oxirane. According to Kissinger method, the reaction activation energy （E,） of two stages were 68.9 and 86.5kJmo1-1, respectively. The Eo of EP/MHHPA and EP/IMA resin system were 81.04 and 77.9kJmol-I. The processing property of EP/RAM/IMA system, i.e. the relationship between viscosity-temperature-time, was characterized by cone-plate viscometer aim to decide the processing parameter ofprepreg preparation. The effect of RAM content on mechanical performance and dynamic mechanical property was investigated. Noteworthily, compared with the laminates with EP/MHHPA as matrix, the laminates with RAM as hardeners achieved a 44%, 73% and 70℃ increase in bending strength, bending modulus and the glass transition temperature, respectively, due to the bulky hydrogenated phenanthrene ring structure incorporated into the cross-linking networks. When the fiber volume fraction reached 47%, the mechanical property of the laminates prepared with hot melt prepreg was superior or comparable to that of composites with pure petroleum sourced matrix. RAM as cross-linking agent of epoxy resin holds a great potential to satisfy the requirement of composites such as structure and secondary structure parts preparation.
文摘The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion(HME).Carbamazepine(CBZ)was selected as model drug and combinations of Kollidon VA64(VA64),Soluplus(SOL)and Eudragit EPO(EPO)were utilized as carriers.Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters,differential scanning calorimetry(DSC),hot stage microscopy and thermogravimetric analysis.Physicochemical properties of solid dispersions were determined by DSC,X-ray diffraction,fourier transform infrared spectroscopy,dissolution and accelerated stability testing.The results show that drug-polymer miscibility at temperatures below the melting point(Tm)of CBZ was improved by combining EPO with VA64 or SOL.With 30%drug loading in a solid dispersion in SOL:EPO(1:1,w/w),CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form.The dissolution rate of the solid dispersion was significantly increased(approximately 90%within 5 min)compared to either the pure drug(approximately 85%within 60 min)or the corresponding physical mixture(approximately 80%within 60 min)before and after storage.The solid dispersion in SOL:EPO(1:1,w/w)was relatively stable at 401C/75%RH under CBZ tablet packaging conditions for at least 3 months.In conclusion,polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.
