To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole(ITZ)/Soluplus~? solid dispersion. Solid dispersions prepared by hot melt extrusion (H...To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole(ITZ)/Soluplus~? solid dispersion. Solid dispersions prepared by hot melt extrusion (HME) were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM). Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox~? in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus~? micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox~?, ITZ tablets exhibited a 2.50-fold increase in the AUC (0–96) of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OHITZ) in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus~? enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer(ABL), resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus~?, which can induce supersaturation by micelleformation, may be of great assistance to the successful development of poorly watersoluble drugs.展开更多
Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalex...Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalexin and controlled by solution feeding rate and seeding conditions. UV and Morphologi G3 were used to measure supersaturation and aspect ratio. Experimental results demonstrated that burst nucleation occurred and the products were needle-like at high supersaturation;meanwhile, the products were plate-like and had high aspect ratio at low supersaturation. Analysis of the measured supersaturation profi les and corresponding aspect ratio explained the mechanisms governing the aspect ratio. The optimized operating parameters were also proposed (seeding supersaturation is equal to 1.3, seed mass ratio 8% and feeding rate 368 μL/min).展开更多
More and more high dams have been constructed and operated in China. The total dissolved gas （TDG） supersaturation caused by dam discharge leads to gas bubble disease or even death of fish, Through a series of exper...More and more high dams have been constructed and operated in China. The total dissolved gas （TDG） supersaturation caused by dam discharge leads to gas bubble disease or even death of fish, Through a series of experiments, the conditions and requirements of supersaturated TDG generation were examined in this study. The results show that pressure （water depth）, aeration, and bubble dissolution time are required for supersaturated TDG generation, and the air-water contact area and turbulence intensity are the main factors that affect the generation rate of supersaturated TDG. The TDG supersaturation levels can be reduced by discharging water to shallow shoals downstream of the dam or using negative pressure pipelines. Furthermore, the TDG supersaturation levels in stilling basins have no direct relationship with those in reservoirs. These results are of great importance for further research on the prediction of supersaturated TDG generation caused by dam discharge and aquatic protection.展开更多
Ice nuclei-supersaturation spectra in the form of a Power Law ( Ni=RSir; B and y are empirical constants) have been expressed since 1973 when the curve was first introduced independentally by Gagin and Huffman. Experi...Ice nuclei-supersaturation spectra in the form of a Power Law ( Ni=RSir; B and y are empirical constants) have been expressed since 1973 when the curve was first introduced independentally by Gagin and Huffman. Experiments performed with a thermal gradient diffusion chamber in order to investigate the validity of the power curve. The results show that a linear curve fit to the data is as good as the power curve. The linear curve has the coefficients of correlation between 0.75 and 0.93 whereas the power curve fit to the same data has the coefficients between 0.82 and 0.93. The data reported by other workers, Zamurs and Jiusto and Zamurs et al., exhibit the same trend.展开更多
Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The sta...Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.展开更多
AIM To demonstrate that urinary supersaturation per se is not a reliable diagnostic measure of the risk for stone formation.METHODS Available physical and chemical data for calcium oxalate monohydrate(COM) and calcium...AIM To demonstrate that urinary supersaturation per se is not a reliable diagnostic measure of the risk for stone formation.METHODS Available physical and chemical data for calcium oxalate monohydrate(COM) and calcium hydrogen phosphate dihydrate(brushite, BRU), and urinary supersaturations with respect to COM and BRU in healthy individuals and stone formers, were obtained from the literature. Classical theory of nucleation was used for calculations.RESULTS It was found that the rate of homogeneous nucleation(unaided by substrates) of COM and BRU is nil at all conceivable supersaturations of urine. Consequently spontaneous formation of crystals in urine requires the presence of nucleation substrates for(heteronuclei).CONCLUSION Urinary supersaturation with respect to lithiatic compounds is a necessary, but not a sufficient condition for nephrolithiasis. The absence of crystallization inhibitors and the presence of efficient nucleation promoters(heteronuclei) in urine are further necessary conditions of urolithiasis occurrence. Urinary supersaturation per se is not a reliable diagnostic measure of the risk of kidney stone formation.展开更多
Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and bioavailability.The growth mechanism of drug spherulite is of great import...Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and bioavailability.The growth mechanism of drug spherulite is of great importance for the preparation and regulation of spherulites.Herein,ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to acetone.Online observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to spherulites.As the supersaturation of the crystallization system was adjusted,the ceftriaxone sodium crystals transformed from amorphous form to spherulites.In the process of antisolvent crystallization with acetone as antisolvent,when the theoretical supersaturation degree S was higher than 2.62,the crystallization system tended to appear amorphous form;when S was between 2.57 and 2.62,the amorphous form transformed into clustered spherulites;when S was less than 2.57,the surface of spherulites will be covered with flaky crystal,which transformed into urchin-like type.With the understanding of the spherical growth mechanism,the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone,and the flowability was significantly improved.展开更多
In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrM...In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrMoCoB heat-resistant steel and CaF_(2)–CaO–Al_(2)O_(3)–SiO_(2)–B_(2)O_(3)electroslag remelting(ESR)-type slag in an 80-t industrial ESR furnace.The main types of NMI in the consumable electrode comprised pure alumina,a multiphase oxide consisting of an Al_(2)O_(3)core and liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO shell,and M_(23)C_(6)carbides with an MnS core.The Al_(2)O_(3)and MnS inclusions had higher precipitation temperatures than the M_(23)C_(6)-type carbide under equilibrium and nonequilibrium solidification processes.Therefore,inclusions can act as nucleation sites for carbide layer precipitation.The ESR process completely removed the liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO oxide and MnS inclusion with a carbide shell,and only the Al_(2)O_(3)inclusions and Al_(2)O_(3)core with a carbide shell occupied the remelted ingot.The M_(23)C_(6)-type carbides in steel were determined as Cr_(23)C_(6)based on the analysis of transmission electron microscopy results.The substitution of Cr with W,Fe,or/and Mo in the Cr_(23)C_(6)lattice caused slight changes in the lattice parameter of the Cr_(23)C_(6)carbide.Therefore,Cr_(21.34)Fe_(1.66)C_(6),(Cr_(19)W_(4)C_(6),Cr_(18.4)Mo_(4.6)C_(6),and Cr_(16)Fe_(5)Mo_(2)C_(6)can match the fraction pattern of Cr_(23)C_(6)carbide.The Al_(2)O_(3)inclusions in the remelted ingot formed due to the reduction of CaO,SiO_(2),and MnO components in the liquid inclusion.The increased Al content in liquid steel or the higher supersaturation degree of Al_(2)O_(3)precipitation in the remelted ingot than that in the electrode can be attributed to the evaporation of CaF_(2)and the increase in CaO content in the ESR-type slag.展开更多
One of the possible negative environmental effects of hydropower stations is the supersaturation of total dissolved gas (TDG) downstream of high-dams,which can lead to gas bubble disease or even death of fish. By taki...One of the possible negative environmental effects of hydropower stations is the supersaturation of total dissolved gas (TDG) downstream of high-dams,which can lead to gas bubble disease or even death of fish. By taking the TDG as the main study object,the paper launched the TDG field observations on Zipingpu,Three Gorges,Ertan,Manwan,Dachaoshan,Gongzui and Ertan dams in China. The factors affecting TDG generation and dissipation were explored. Energy dissipation structures,spill rates and operation patterns were the main factors causing TDG supersaturation. TDG saturations are essentially the same in the hydro-electric tail water and in the upper reaches,so hydro-electric tail water can be less TDG supersaturated through mixing downstream. The main factors affecting the dissipation process of the supersaturated TDG were tributary convergence,water depth and turbulence. TDG supersaturation was unevenly distributed in both the vertical and transverse directions. This study is important because it adds to the accumulating experience of TDG field observations of dam projects in China,and because it objectively and impartially evaluates the impacts of supersaturated TDG. The study also provides field data and references for future studies of TDG supersaturation caused by high-dams.展开更多
Laboratory experiments were conducted to determine the effects of total dissolved gas （TDG） supersaturation on acute lethality and avoidance responses in juvenile rock carp （Procypris rabaudi Tchang）. The juvenile...Laboratory experiments were conducted to determine the effects of total dissolved gas （TDG） supersaturation on acute lethality and avoidance responses in juvenile rock carp （Procypris rabaudi Tchang）. The juvenile rock carp were exposed to water with different levels of supersaturation （105%, 115%, 120%, 125%, 130%, 135%, 140%, and 145%） and depth of 0.20 m at 25℃ for 60 h. Median lethal time （LT50） was used to assess the lethal responses corresponding to different levels of gas supersaturation. The results show that half of the juvenile rock carp died at the 120%, 125%, 130%, 135%, 140%, and 145% levels of supersaturation, and the LT50 corresponding to different levels of supersaturation was 18.7, 15.4, 8.2, 6.6, 3.5, and 1.7 h. When the level of supersaturated water is below 115%, the mortality is negligible. Avoidance responses were observed 5 min after the fish were put into equilibrated water （99%, 0.08 m deep） and water with different supersaturated levels （105%, 115%, 125%, 135%, and 145%, 0.08 m deep） at 25 ℃. The fish exhibited strong avoidance responses in supersaturated water when the gas supersaturation was above 135%. However, they exhibited an obvious preference to supersaturated water when the gas supersaturation was below 115%. Thus, the juvenile rock carp can likely survive in water with a supersaturated level of 115%.展开更多
Controlling the nucleation and growth of organic-inorganic hybrids perovskite is of key importance to improve the morphology and crystallinity of perovskite films. However, the growth mechanism of perovskite films bas...Controlling the nucleation and growth of organic-inorganic hybrids perovskite is of key importance to improve the morphology and crystallinity of perovskite films. However, the growth mechanism of perovskite films based on classical crystallization theory is not fully understood. Here, we develop a supersaturation controlled strategy(SCS) to balance the nucleation and crystal growth speeds. By this strategy, we are able to find an ideal supersaturation region to realize a balance of nucleation and crystal growth, which yields highly crystallized perovskite films with micrometer-scale grains. Besides, we provide a thoughtful analysis of nucleation and growth based on the fabrication of the perovskite films. As a result, the highest photovoltaic power conversion efficiencies(PCE) of 19.70% and 20.31% are obtained for the planar and the meso-superstructured devices, respectively. This strategy sheds some light for understanding the film growth mechanism of high quality perovskite film, and it provides a facile strategy to fabricate high efficiency perovskite solar cells.展开更多
Swift cooling crystallization of vanillin was investigated in water,ethanol,isopropanol and ethyl acetate.Morphology and polymorph evolution of vanillin were discussed in terms of solvent,supersaturation ratio and sil...Swift cooling crystallization of vanillin was investigated in water,ethanol,isopropanol and ethyl acetate.Morphology and polymorph evolution of vanillin were discussed in terms of solvent,supersaturation ratio and silica template.PXRD,DSC,FTIR and microscope were used to identify polymorphs of vanillin.Results showed that the nucleated polymorphs of vanillin depended largely on the solvent,supersaturation ratio and silica template.Low supersaturation ratios favor the nucleation of stable form I in water,and high supersaturation ratio exceeds 7 generating 100%metastable form II.However,if the supersaturation ratio is too high(S>8),liquid-liquid phase separation will occur,and no crystals could be obtained.In other solvents such as ethanol,isopropanol and ethyl acetate,only form I was obtained.However,it should be noted that the morphology of form I prepared in ethanol,isopropanol and ethyl acetate is distinct from that obtained in water,the former is flake-like and the latter is rod-like.The nucleation of vanillin from different solution was also studied with the presence of SiO_(2),SiO_(2)-NH_(2)and SiO_(2)−COOH templates,which did not change the nucleated polymorph of vanillin,but changed the nucleation and growth rate of stable form I.展开更多
In order to realize accurate dynamic control of supersaturation and to study condensation growth characteristics of nanoparticles through different levels of super saturation,a series of parametric analyses and system...In order to realize accurate dynamic control of supersaturation and to study condensation growth characteristics of nanoparticles through different levels of super saturation,a series of parametric analyses and systematic comparisons between two-stage and three-stage operating temperature designs were simulated with COMSOL Multiphysics.The simulation results showed that the three-stage operating temperature did not change peak supersaturation compared with two operating temperatures,and the three-stage operating temperature was superior in decreasing the amount of water vapor and the temperature,thus lowering particle loss and variation in detection and collection.The peak supersaturation level increased by 0.3 as the flow rate increased from 0.6 to 2.0 L/min,but the supersaturation peak moved from 0.0027 z0 to 0.08 z0(i.e.,the growth time and the final size decreased by 40%).Peak supersaturation increased as the temperature difference increased or the temperature difference window was shifting left,and minimum activation size decreased.Shifting the 70℃temperature difference window from 9℃,79℃-1℃,71℃for the condenser and initiator temperatures resulted in peak supersaturation in the centerline being above 5.8,and the activation size changed as low as 1 nm.Experiments with flow rates varying by a factor of 2.5(from 0.6 to 1.5 L/min)resulted in a final size decrease of 43%(from 3.2 to 1.8μm),and experimental results of outlet particle size distributions were equivalent with theoretical analysis as the operating temperature was changed.展开更多
Lithium-sulfur(Li-S)batteries have attracted extensive attention due to ultrahigh theoretical energy density of 2600 Wh kg^(-1).Liquid-solid deposition from dissolved lithium polysulfides(LiPSs)to solid lithium sulfid...Lithium-sulfur(Li-S)batteries have attracted extensive attention due to ultrahigh theoretical energy density of 2600 Wh kg^(-1).Liquid-solid deposition from dissolved lithium polysulfides(LiPSs)to solid lithium sulfide(Li_(2)S)largely determines the actual battery performances.Herein,a premature liquidsolid deposition process of LiPSs is revealed at higher thermodynamic potential than Li_(2)S deposition in Li-S batteries.The premature solid deposit exhibits higher chemical state and hemispherical morphology in comparison with Li_(2)S,and the premature deposition process is slower in kinetics and higher in deposition dimension.Accordingly,a supersaturation deposition mechanism is proposed to rationalize the above findings based on thermodynamic simulation.This work demonstrates a unique premature liquid-solid deposition process of Li-S batteries.展开更多
Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes ...Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities.Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.Methods: All relevant literature up to October 2020,listed in PubMed is reviewed.Results: Clinical guidelines endorse the use of evidence-based medications,such as alkaline agents and thiazides,to reduce urinary mineral supersaturation and recurrence.However,there may be additional steps during stone pathogenesis where medications could moderate stone risk.Idiopathic calcium oxalate stones grow attached to Randall’s plaques or plugs.Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs.The renin-angiotensin-aldosterone system(RAAS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,mitochondria,and NOD-like receptor pyrin domain containing-3(NLRP3)inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.Conclusion: In addition to supersaturation-reducing therapies,the use of anti-oxidants,free radical scavengers,and inhibitors of NADPH oxidase,NLRP3 inflammasome,and RAAS may prove beneficial for stone prevention.Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats.Although clinical evidence for their use in stone prevention in humans is limited,experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.展开更多
This experiment examined the fluctuations in nitrogen gas supersaturation throughout the day in three karst springs (upper, side, and lower) at McNenny State Fish Hatchery, rural Spearfish, Lawrence County, South Dako...This experiment examined the fluctuations in nitrogen gas supersaturation throughout the day in three karst springs (upper, side, and lower) at McNenny State Fish Hatchery, rural Spearfish, Lawrence County, South Dakota, USA. Total gas pressures, oxygen percent saturation, and nitrogen percent saturation were recorded six times/day on eight days over a 26-day period in each of the three springs. Total gas pressure did not vary significantly throughout the day in any of the springs. However, percent oxygen and nitrogen saturation were significantly different throughout the day in all three springs. The highest mean (SE) nitrogen supersaturation value of 118.5 (1.1)% was observed in the lower spring at 07:00. The lowest mean nitrogen supersaturation values were 114.5 (1.1)% at 13:00 in the upper spring, and 114.2 (0.2)% and 113.1 (0.7)% at 15:00 in the side and lower spring, respectively. At 118% nitrogen supersaturation, gas bubble disease is likely to occur in fish, resulting in potentially high levels of mortality if untreated spring water was used for fish production. The results of this study indicate the importance of recording nitrogen gas levels at sunrise or early in the morning, when nitrogen is highest and oxygen is lowest, to obtain accurate and reproducible data.展开更多
Methanol synthesis catalysts based on Cu, Zn and Al were prepared by three methods and subsequently mixed with H-ferrierite zeolite in an aqueous suspension to disperse the catalysts over the support. These materials ...Methanol synthesis catalysts based on Cu, Zn and Al were prepared by three methods and subsequently mixed with H-ferrierite zeolite in an aqueous suspension to disperse the catalysts over the support. These materials were characterized by X-ray diffraction, N2 adsorption, transmission electron microscopy, temperature programmed reduction, NH3 and H2 temperature-programmed desorption, and X-ray photoelectron spectroscopy. They were also applied to the CO hydrogenation reaction to produce dimethyl ether and hydrocarbons. The catalysts were prepared by coprecipitation under low and high supersaturation conditions and by a homogeneous precipitation method. The preparation technique was found to affect the precursor structural characteristics, such as purity and crystallinity, as well as the particle size distribution of the resulting catalyst. Low supersaturation conditions favored high dispersion of the Cu species, increasing the methanol synthesis catalyst＇s metallic surface area and resulting in a homogeneous particle size distribution. These effects in turn were found to modify the zeolite properties, promoting both a low micropore volume and blockage of the zeolite acid sites. The effect of the methanol synthesis catalyst on the reaction was verified by the correlation between the Cu surface area and the CO conversion rate.展开更多
The effect of mixing on the precipitation of barium sulfate in a continuous stirred tank is simulated numerically with different feeding location, feed concentration, impeller speed and residence time through solving ...The effect of mixing on the precipitation of barium sulfate in a continuous stirred tank is simulated numerically with different feeding location, feed concentration, impeller speed and residence time through solving the standard momentum and mass transport equations in combination with the moment equations for crystal population balance. The numerical method was validated with the literature data. The simulation results including the distribution of the local supersaturation ratio distribution in the precipitator, mean crystal size and coefficient of variation under different operating conditions compared well with experimental data in the literature. The effect of the presence of a draft tube on precipitation were also investigated, and it is suggested that the installation of a draft tube increased the mean crystal size, in general agreement with experimental work in the literature.展开更多
The recrystallization process of a rapidly solidified Cu-Cr-Zr-Mg alloy during its aging was investigate experimentally. It was found that (1) upon aging, the precipitation process takes place prior to recrystallizati...The recrystallization process of a rapidly solidified Cu-Cr-Zr-Mg alloy during its aging was investigate experimentally. It was found that (1) upon aging, the precipitation process takes place prior to recrystallization for the cold-deformed Cu-Cr-Zr-Mg alloy produced by rapid solidification, and the precipitates have a restrained effect on the following recrystallization process; (2) the hindrance of the dispersed fine precipitates to the common recrystallization leads to the simultaneous in situ and discontinuous recrystallization; (3) the resolution of the precipitates in the front of migrating grain boundaries takes place during the nucleation and growth of recrystallization, which results in a supersaturation in the recrystallized zones, while the re-precipitation of the supersaturated solute atoms in vacancies further increases the dispersion hardening effect.展开更多
Cellulose derivatives have gained immense popularity as stabilizers for amorphous solid dispersion owing to their diverse physicochemical properties. More than 20 amorphous solid dispersion-based products that have be...Cellulose derivatives have gained immense popularity as stabilizers for amorphous solid dispersion owing to their diverse physicochemical properties. More than 20 amorphous solid dispersion-based products that have been approved for marketing consist of cellulose derivatives as stabilizers, thus highlighting their importance in generation of amorphous solid dispersions. These polymers offer numerous advantages like drug solubilization, crystallization inhibition and improvement in release patterns of drugs. Exploring their potential and exploiting their chemistry and p H responsive behaviour have led to the synthesis of new derivatives that has broadened the scope of the use of cellulose derivatives in amorphous formulation development. The present review aims to provide an overview of different mechanisms by which these cellulose derivatives inhibit the crystallization of drugs in the solid state and from supersaturated solution. A summary of different categories of cellulose derivatives along with the newly explored polymers has been provided. A special segment on strengths, weaknesses, opportunities, and threats(SWOT) analysis and critical quality attributes(CQAs) which affect the performance of the cellulose based amorphous solid dispersion will aid the researchers in identifying the major challenges in the development of cellulose based solid dispersion and serve as a guide for further formulation development.展开更多
基金the National Natural Science Foundation of China(NSFC 81102399).
文摘To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole(ITZ)/Soluplus~? solid dispersion. Solid dispersions prepared by hot melt extrusion (HME) were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM). Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox~? in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus~? micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox~?, ITZ tablets exhibited a 2.50-fold increase in the AUC (0–96) of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OHITZ) in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus~? enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer(ABL), resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus~?, which can induce supersaturation by micelleformation, may be of great assistance to the successful development of poorly watersoluble drugs.
基金supported by the Major National Science and Technology Projects (No. 2017ZX07402003)Major National Scientifi c Instrument Development Project (No. 21527812)
文摘Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalexin and controlled by solution feeding rate and seeding conditions. UV and Morphologi G3 were used to measure supersaturation and aspect ratio. Experimental results demonstrated that burst nucleation occurred and the products were needle-like at high supersaturation;meanwhile, the products were plate-like and had high aspect ratio at low supersaturation. Analysis of the measured supersaturation profi les and corresponding aspect ratio explained the mechanisms governing the aspect ratio. The optimized operating parameters were also proposed (seeding supersaturation is equal to 1.3, seed mass ratio 8% and feeding rate 368 μL/min).
基金supported by the National Natural Science Foundation of China (Grant No. 50979063)
文摘More and more high dams have been constructed and operated in China. The total dissolved gas （TDG） supersaturation caused by dam discharge leads to gas bubble disease or even death of fish, Through a series of experiments, the conditions and requirements of supersaturated TDG generation were examined in this study. The results show that pressure （water depth）, aeration, and bubble dissolution time are required for supersaturated TDG generation, and the air-water contact area and turbulence intensity are the main factors that affect the generation rate of supersaturated TDG. The TDG supersaturation levels can be reduced by discharging water to shallow shoals downstream of the dam or using negative pressure pipelines. Furthermore, the TDG supersaturation levels in stilling basins have no direct relationship with those in reservoirs. These results are of great importance for further research on the prediction of supersaturated TDG generation caused by dam discharge and aquatic protection.
文摘Ice nuclei-supersaturation spectra in the form of a Power Law ( Ni=RSir; B and y are empirical constants) have been expressed since 1973 when the curve was first introduced independentally by Gagin and Huffman. Experiments performed with a thermal gradient diffusion chamber in order to investigate the validity of the power curve. The results show that a linear curve fit to the data is as good as the power curve. The linear curve has the coefficients of correlation between 0.75 and 0.93 whereas the power curve fit to the same data has the coefficients between 0.82 and 0.93. The data reported by other workers, Zamurs and Jiusto and Zamurs et al., exhibit the same trend.
基金by the National Natural Science Foundation of China(No.82173765)the Science Foundation for Outstanding Youth of Liaoning Province(2021-YQ-08)+5 种基金Ningxia Key Research and Invention Program(No.2021BEG02039)Basic Research Projects of Liaoning Provincial Department of Education(2020LFW01)the Career Development Program for Young Teachers in Shenyang Pharmaceutical University(ZQN2019003)the Outstanding Youth Lifting Program in Shenyang Pharmaceutical University(YQ202115)the Natural Science Foundation of Liaoning Province(2020-MS-074)Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(Dalian Minzu University),Ministry of Education(KF2022005),China.
文摘Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.
文摘AIM To demonstrate that urinary supersaturation per se is not a reliable diagnostic measure of the risk for stone formation.METHODS Available physical and chemical data for calcium oxalate monohydrate(COM) and calcium hydrogen phosphate dihydrate(brushite, BRU), and urinary supersaturations with respect to COM and BRU in healthy individuals and stone formers, were obtained from the literature. Classical theory of nucleation was used for calculations.RESULTS It was found that the rate of homogeneous nucleation(unaided by substrates) of COM and BRU is nil at all conceivable supersaturations of urine. Consequently spontaneous formation of crystals in urine requires the presence of nucleation substrates for(heteronuclei).CONCLUSION Urinary supersaturation with respect to lithiatic compounds is a necessary, but not a sufficient condition for nephrolithiasis. The absence of crystallization inhibitors and the presence of efficient nucleation promoters(heteronuclei) in urine are further necessary conditions of urolithiasis occurrence. Urinary supersaturation per se is not a reliable diagnostic measure of the risk of kidney stone formation.
基金the financial contribution from Central Guidance on Local Science and Technology Development Fund of Liaoning Province(grant No.2023JH6/100100004)National Key Research and Development Program of China(grant No.2021YFC2901300)+3 种基金National Natural Science Foundation of China(grant No.22021005,22378041)Fundamental Research Funds for the Central Universities(grant No.DUT22YG208,DUT22LAB603)Key Research and Development Projects in Shandong Province(grant No.2022CXGC010303)acknowledge the assistance of Dalian University of Technology Instrumental Analysis Center.
文摘Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and bioavailability.The growth mechanism of drug spherulite is of great importance for the preparation and regulation of spherulites.Herein,ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to acetone.Online observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to spherulites.As the supersaturation of the crystallization system was adjusted,the ceftriaxone sodium crystals transformed from amorphous form to spherulites.In the process of antisolvent crystallization with acetone as antisolvent,when the theoretical supersaturation degree S was higher than 2.62,the crystallization system tended to appear amorphous form;when S was between 2.57 and 2.62,the amorphous form transformed into clustered spherulites;when S was less than 2.57,the surface of spherulites will be covered with flaky crystal,which transformed into urchin-like type.With the understanding of the spherical growth mechanism,the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone,and the flowability was significantly improved.
基金the Korea Evaluation Institute of Industrial Technology(KEIT,No.20009956)the Korea Institute for Advancement of Technology(KIAT,No.P0023676,HRD Program for Industrial Innovation)+1 种基金funded by the Ministry of Trade,Industry and Energy(MOTIE),Koreathe Swedish Foundation for International Cooperation in Research and Higher Education(STINT)for supporting the collaboration between KTH(Sweden)and Hanyang University(Korea)。
文摘In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrMoCoB heat-resistant steel and CaF_(2)–CaO–Al_(2)O_(3)–SiO_(2)–B_(2)O_(3)electroslag remelting(ESR)-type slag in an 80-t industrial ESR furnace.The main types of NMI in the consumable electrode comprised pure alumina,a multiphase oxide consisting of an Al_(2)O_(3)core and liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO shell,and M_(23)C_(6)carbides with an MnS core.The Al_(2)O_(3)and MnS inclusions had higher precipitation temperatures than the M_(23)C_(6)-type carbide under equilibrium and nonequilibrium solidification processes.Therefore,inclusions can act as nucleation sites for carbide layer precipitation.The ESR process completely removed the liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO oxide and MnS inclusion with a carbide shell,and only the Al_(2)O_(3)inclusions and Al_(2)O_(3)core with a carbide shell occupied the remelted ingot.The M_(23)C_(6)-type carbides in steel were determined as Cr_(23)C_(6)based on the analysis of transmission electron microscopy results.The substitution of Cr with W,Fe,or/and Mo in the Cr_(23)C_(6)lattice caused slight changes in the lattice parameter of the Cr_(23)C_(6)carbide.Therefore,Cr_(21.34)Fe_(1.66)C_(6),(Cr_(19)W_(4)C_(6),Cr_(18.4)Mo_(4.6)C_(6),and Cr_(16)Fe_(5)Mo_(2)C_(6)can match the fraction pattern of Cr_(23)C_(6)carbide.The Al_(2)O_(3)inclusions in the remelted ingot formed due to the reduction of CaO,SiO_(2),and MnO components in the liquid inclusion.The increased Al content in liquid steel or the higher supersaturation degree of Al_(2)O_(3)precipitation in the remelted ingot than that in the electrode can be attributed to the evaporation of CaF_(2)and the increase in CaO content in the ESR-type slag.
基金supported by the National Natural Science Foundation of China (Grant No.50979063)
文摘One of the possible negative environmental effects of hydropower stations is the supersaturation of total dissolved gas (TDG) downstream of high-dams,which can lead to gas bubble disease or even death of fish. By taking the TDG as the main study object,the paper launched the TDG field observations on Zipingpu,Three Gorges,Ertan,Manwan,Dachaoshan,Gongzui and Ertan dams in China. The factors affecting TDG generation and dissipation were explored. Energy dissipation structures,spill rates and operation patterns were the main factors causing TDG supersaturation. TDG saturations are essentially the same in the hydro-electric tail water and in the upper reaches,so hydro-electric tail water can be less TDG supersaturated through mixing downstream. The main factors affecting the dissipation process of the supersaturated TDG were tributary convergence,water depth and turbulence. TDG supersaturation was unevenly distributed in both the vertical and transverse directions. This study is important because it adds to the accumulating experience of TDG field observations of dam projects in China,and because it objectively and impartially evaluates the impacts of supersaturated TDG. The study also provides field data and references for future studies of TDG supersaturation caused by high-dams.
基金Project (No. 50979063) supported by the National Natural Science Foundation of China
文摘Laboratory experiments were conducted to determine the effects of total dissolved gas （TDG） supersaturation on acute lethality and avoidance responses in juvenile rock carp （Procypris rabaudi Tchang）. The juvenile rock carp were exposed to water with different levels of supersaturation （105%, 115%, 120%, 125%, 130%, 135%, 140%, and 145%） and depth of 0.20 m at 25℃ for 60 h. Median lethal time （LT50） was used to assess the lethal responses corresponding to different levels of gas supersaturation. The results show that half of the juvenile rock carp died at the 120%, 125%, 130%, 135%, 140%, and 145% levels of supersaturation, and the LT50 corresponding to different levels of supersaturation was 18.7, 15.4, 8.2, 6.6, 3.5, and 1.7 h. When the level of supersaturated water is below 115%, the mortality is negligible. Avoidance responses were observed 5 min after the fish were put into equilibrated water （99%, 0.08 m deep） and water with different supersaturated levels （105%, 115%, 125%, 135%, and 145%, 0.08 m deep） at 25 ℃. The fish exhibited strong avoidance responses in supersaturated water when the gas supersaturation was above 135%. However, they exhibited an obvious preference to supersaturated water when the gas supersaturation was below 115%. Thus, the juvenile rock carp can likely survive in water with a supersaturated level of 115%.
基金supported by the National Key Research and Development Program of China (2016YFA0204000)the National Natural Science Foundation of China (U1632118, 21571129)+2 种基金Shanghai Tech Start-Up Funding1000 Young Talent program,Science and Technology Commission of Shanghai Municipality (16JC1402100, 16520720700)
文摘Controlling the nucleation and growth of organic-inorganic hybrids perovskite is of key importance to improve the morphology and crystallinity of perovskite films. However, the growth mechanism of perovskite films based on classical crystallization theory is not fully understood. Here, we develop a supersaturation controlled strategy(SCS) to balance the nucleation and crystal growth speeds. By this strategy, we are able to find an ideal supersaturation region to realize a balance of nucleation and crystal growth, which yields highly crystallized perovskite films with micrometer-scale grains. Besides, we provide a thoughtful analysis of nucleation and growth based on the fabrication of the perovskite films. As a result, the highest photovoltaic power conversion efficiencies(PCE) of 19.70% and 20.31% are obtained for the planar and the meso-superstructured devices, respectively. This strategy sheds some light for understanding the film growth mechanism of high quality perovskite film, and it provides a facile strategy to fabricate high efficiency perovskite solar cells.
基金This work was financially supported by grants from the National Natural Science Foundation of China(grant Nos.22068002 and 22178054)Natural Science Foundation of Jiangxi Province(grant No.20202BABL203020)。
文摘Swift cooling crystallization of vanillin was investigated in water,ethanol,isopropanol and ethyl acetate.Morphology and polymorph evolution of vanillin were discussed in terms of solvent,supersaturation ratio and silica template.PXRD,DSC,FTIR and microscope were used to identify polymorphs of vanillin.Results showed that the nucleated polymorphs of vanillin depended largely on the solvent,supersaturation ratio and silica template.Low supersaturation ratios favor the nucleation of stable form I in water,and high supersaturation ratio exceeds 7 generating 100%metastable form II.However,if the supersaturation ratio is too high(S>8),liquid-liquid phase separation will occur,and no crystals could be obtained.In other solvents such as ethanol,isopropanol and ethyl acetate,only form I was obtained.However,it should be noted that the morphology of form I prepared in ethanol,isopropanol and ethyl acetate is distinct from that obtained in water,the former is flake-like and the latter is rod-like.The nucleation of vanillin from different solution was also studied with the presence of SiO_(2),SiO_(2)-NH_(2)and SiO_(2)−COOH templates,which did not change the nucleated polymorph of vanillin,but changed the nucleation and growth rate of stable form I.
基金supported by Natural Science Foundation of China(No.91544218)the National Key Research and Development Program of China(No.2016YFC0201001)+2 种基金the Science and Technological Fund of Anhui Province for Outstanding Youth(1808085J19)the Science and Technological Fund of Anhui Province(1908085MD114)The CASHIPS Director’s Fund,Grant NO.YZJJ2019QN1
文摘In order to realize accurate dynamic control of supersaturation and to study condensation growth characteristics of nanoparticles through different levels of super saturation,a series of parametric analyses and systematic comparisons between two-stage and three-stage operating temperature designs were simulated with COMSOL Multiphysics.The simulation results showed that the three-stage operating temperature did not change peak supersaturation compared with two operating temperatures,and the three-stage operating temperature was superior in decreasing the amount of water vapor and the temperature,thus lowering particle loss and variation in detection and collection.The peak supersaturation level increased by 0.3 as the flow rate increased from 0.6 to 2.0 L/min,but the supersaturation peak moved from 0.0027 z0 to 0.08 z0(i.e.,the growth time and the final size decreased by 40%).Peak supersaturation increased as the temperature difference increased or the temperature difference window was shifting left,and minimum activation size decreased.Shifting the 70℃temperature difference window from 9℃,79℃-1℃,71℃for the condenser and initiator temperatures resulted in peak supersaturation in the centerline being above 5.8,and the activation size changed as low as 1 nm.Experiments with flow rates varying by a factor of 2.5(from 0.6 to 1.5 L/min)resulted in a final size decrease of 43%(from 3.2 to 1.8μm),and experimental results of outlet particle size distributions were equivalent with theoretical analysis as the operating temperature was changed.
基金supported by the National Key Research and Development Program(2021YFB2400300)the Beijing Natural Science Foundation(JQ20004)+1 种基金the National Natural Science Foundation of China(22109007,22109011)the Beijing Institute of Technology Research Fund Program for Young Scholars。
文摘Lithium-sulfur(Li-S)batteries have attracted extensive attention due to ultrahigh theoretical energy density of 2600 Wh kg^(-1).Liquid-solid deposition from dissolved lithium polysulfides(LiPSs)to solid lithium sulfide(Li_(2)S)largely determines the actual battery performances.Herein,a premature liquidsolid deposition process of LiPSs is revealed at higher thermodynamic potential than Li_(2)S deposition in Li-S batteries.The premature solid deposit exhibits higher chemical state and hemispherical morphology in comparison with Li_(2)S,and the premature deposition process is slower in kinetics and higher in deposition dimension.Accordingly,a supersaturation deposition mechanism is proposed to rationalize the above findings based on thermodynamic simulation.This work demonstrates a unique premature liquid-solid deposition process of Li-S batteries.
文摘Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities.Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.Methods: All relevant literature up to October 2020,listed in PubMed is reviewed.Results: Clinical guidelines endorse the use of evidence-based medications,such as alkaline agents and thiazides,to reduce urinary mineral supersaturation and recurrence.However,there may be additional steps during stone pathogenesis where medications could moderate stone risk.Idiopathic calcium oxalate stones grow attached to Randall’s plaques or plugs.Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs.The renin-angiotensin-aldosterone system(RAAS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,mitochondria,and NOD-like receptor pyrin domain containing-3(NLRP3)inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.Conclusion: In addition to supersaturation-reducing therapies,the use of anti-oxidants,free radical scavengers,and inhibitors of NADPH oxidase,NLRP3 inflammasome,and RAAS may prove beneficial for stone prevention.Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats.Although clinical evidence for their use in stone prevention in humans is limited,experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.
文摘This experiment examined the fluctuations in nitrogen gas supersaturation throughout the day in three karst springs (upper, side, and lower) at McNenny State Fish Hatchery, rural Spearfish, Lawrence County, South Dakota, USA. Total gas pressures, oxygen percent saturation, and nitrogen percent saturation were recorded six times/day on eight days over a 26-day period in each of the three springs. Total gas pressure did not vary significantly throughout the day in any of the springs. However, percent oxygen and nitrogen saturation were significantly different throughout the day in all three springs. The highest mean (SE) nitrogen supersaturation value of 118.5 (1.1)% was observed in the lower spring at 07:00. The lowest mean nitrogen supersaturation values were 114.5 (1.1)% at 13:00 in the upper spring, and 114.2 (0.2)% and 113.1 (0.7)% at 15:00 in the side and lower spring, respectively. At 118% nitrogen supersaturation, gas bubble disease is likely to occur in fish, resulting in potentially high levels of mortality if untreated spring water was used for fish production. The results of this study indicate the importance of recording nitrogen gas levels at sunrise or early in the morning, when nitrogen is highest and oxygen is lowest, to obtain accurate and reproducible data.
文摘Methanol synthesis catalysts based on Cu, Zn and Al were prepared by three methods and subsequently mixed with H-ferrierite zeolite in an aqueous suspension to disperse the catalysts over the support. These materials were characterized by X-ray diffraction, N2 adsorption, transmission electron microscopy, temperature programmed reduction, NH3 and H2 temperature-programmed desorption, and X-ray photoelectron spectroscopy. They were also applied to the CO hydrogenation reaction to produce dimethyl ether and hydrocarbons. The catalysts were prepared by coprecipitation under low and high supersaturation conditions and by a homogeneous precipitation method. The preparation technique was found to affect the precursor structural characteristics, such as purity and crystallinity, as well as the particle size distribution of the resulting catalyst. Low supersaturation conditions favored high dispersion of the Cu species, increasing the methanol synthesis catalyst＇s metallic surface area and resulting in a homogeneous particle size distribution. These effects in turn were found to modify the zeolite properties, promoting both a low micropore volume and blockage of the zeolite acid sites. The effect of the methanol synthesis catalyst on the reaction was verified by the correlation between the Cu surface area and the CO conversion rate.
基金Supported by the National Natural Science Foundation of China (Nos.20236050, 50134020) and the Special Funds for Major State Basic Research Program of China (973 Program, 2004CB217604).
文摘The effect of mixing on the precipitation of barium sulfate in a continuous stirred tank is simulated numerically with different feeding location, feed concentration, impeller speed and residence time through solving the standard momentum and mass transport equations in combination with the moment equations for crystal population balance. The numerical method was validated with the literature data. The simulation results including the distribution of the local supersaturation ratio distribution in the precipitator, mean crystal size and coefficient of variation under different operating conditions compared well with experimental data in the literature. The effect of the presence of a draft tube on precipitation were also investigated, and it is suggested that the installation of a draft tube increased the mean crystal size, in general agreement with experimental work in the literature.
文摘The recrystallization process of a rapidly solidified Cu-Cr-Zr-Mg alloy during its aging was investigate experimentally. It was found that (1) upon aging, the precipitation process takes place prior to recrystallization for the cold-deformed Cu-Cr-Zr-Mg alloy produced by rapid solidification, and the precipitates have a restrained effect on the following recrystallization process; (2) the hindrance of the dispersed fine precipitates to the common recrystallization leads to the simultaneous in situ and discontinuous recrystallization; (3) the resolution of the precipitates in the front of migrating grain boundaries takes place during the nucleation and growth of recrystallization, which results in a supersaturation in the recrystallized zones, while the re-precipitation of the supersaturated solute atoms in vacancies further increases the dispersion hardening effect.
基金financial support from the De-partment of Pharmaceuticals(Do P),Ministry of Chemicals and Fertilizers,Govt.of India
文摘Cellulose derivatives have gained immense popularity as stabilizers for amorphous solid dispersion owing to their diverse physicochemical properties. More than 20 amorphous solid dispersion-based products that have been approved for marketing consist of cellulose derivatives as stabilizers, thus highlighting their importance in generation of amorphous solid dispersions. These polymers offer numerous advantages like drug solubilization, crystallization inhibition and improvement in release patterns of drugs. Exploring their potential and exploiting their chemistry and p H responsive behaviour have led to the synthesis of new derivatives that has broadened the scope of the use of cellulose derivatives in amorphous formulation development. The present review aims to provide an overview of different mechanisms by which these cellulose derivatives inhibit the crystallization of drugs in the solid state and from supersaturated solution. A summary of different categories of cellulose derivatives along with the newly explored polymers has been provided. A special segment on strengths, weaknesses, opportunities, and threats(SWOT) analysis and critical quality attributes(CQAs) which affect the performance of the cellulose based amorphous solid dispersion will aid the researchers in identifying the major challenges in the development of cellulose based solid dispersion and serve as a guide for further formulation development.
