Particle Dissolution Rate Research Articles

Supercritical CO2 assisted bioMOF drug encapsulation and functionalization for delivery with a synergetic therapeutic value

Despite the impressive characteristics of biological metal organic frameworks (bioMOFs) for their use as drug delivery systems (DDs), there are still some parameters related to their structural stability and processing routes that have decelerated their realistic application in this field. Both drawbacks are unraveled in this work for the microporous bioMOF CaSyr-1 by using supercritical CO2 (scCO2) to load the bioMOF with the anti-tubercular isoniazid (INH) drug, and functionalize its external surface with a hydrophobic protective layer of stearate (S). The hydrophobicized CaSyr-1(INH)/S vehicle is further coated with a neutral surfactant (PS60) to enhance the wettability of the system. In vitro tests, related to drug carrier biocompatibility and drug release in body simulated fluids, are performed to demonstrate potential prospective of the designed DDs in pharmacy. The synthetized product displayed total biocompatibility even at high concentrations, and the particle size and dissolution rate showed to be adequate for pulmonary administration.

Modeling and Parametric Study of Spent Refractory Material Dissolution in an Aluminum Reduction Cell

Utilizing spent refractory material (SRM), generated after the overhaul of aluminum electrolytic cells, as a raw material for producing Al-Si alloys presents an efficient approach towards achieving full resource utilization of SRM. However, a bottleneck restricting this technology has become the dissolution of SRM. Based on the heat and mass transfer mechanism, the shrinkage core model of SRM particle dissolution was established. The effects of alumina concentration, silica concentration, electrolyte superheat, particle temperature, and turbulent kinetic energy dissipation rate on the mass dissolution rate and dissolution time of SRM particles were investigated. Calculation results and experimental data were compared to confirm the accuracy of the established model. The results show that by maintaining low alumina and silica concentrations, increasing the electrolyte superheat and particle preheating temperature, and increasing the electrolyte turbulent kinetic energy dissipation rate, SRM particles can dissolve faster. The dissolution of agglomerated particles is greatly influenced by the turbulent kinetic energy dissipation rate and superheat. The present research provides promising guidance for practical application in predicting particle dissolution time, controlling process parameters, and accelerating the dissolution of SRM particles.

The Particle Drifting Effect: A Combined Function of Colloidal and Drug Properties.

The particle drifting effect, where nanosized colloidal drug particles overcome the diffusional resistance of the aqueous boundary layer adjacent to the intestinal wall and increase drug absorption rates, is drawing increasing attention in pharmaceutical research. However, mechanistic understanding and accurate prediction of the particle drifting effect remain lacking. In this study, we systematically evaluated the extent of the particle drifting effect affected by drug and colloidal properties, including the size, number, and type of the moving species using biphasic diffusion experiments combined with computational fluid dynamics simulations and mass transport analyses. The results showed that the particle drifting effect is a sequential reaction of particle dissolution/dissociation in the diffusional boundary layer, followed by absorption of the free drug. Therefore, factors affecting the rate-limiting step, which can be either process or both under different circumstances, alter the particle drifting effect. Experimental results also agree with the theory that the particle dissolution rate is dependent on particle size, concentration, and drug solubility. In addition, rapid bile micelle dissociation and bile salt absorption facilitated drug absorption by the particle drifting effect. Our findings explain the highly dynamic nature of the particle drifting effect and will contribute to rational formulation development and better bioavailability prediction for formulations containing colloidal particles.

Deep learning revealed statistics of the MgO particles dissolution rate in a CaO–Al2O3–SiO2–MgO slag

Accelerated material development for refractory ceramics triggers possibilities in context to enhanced energy efficiency for industrial processes. Here, the gathering of comprehensive material data is essential. High temperature-confocal laser scanning microscopy (HT-CLSM) displays a highly suitable in-situ method to study the underlying dissolution kinetics in the slag over time. A major drawback concerns the efficient and accurate processing of the collected image data. Here, we introduce an attention encoder–decoder convolutional neural network enabling the fully automated evaluation of the particle dissolution rate with a precision of 99.1%. The presented approach provides accurate and efficient analysis capabilities with high statistical gain and is highly resilient to image quality changes. The prediction model allows an automated diameter evaluation of the MgO particles' dissolution in the silicate slag for different temperature settings and various HT-CLSM data sets. Moreover, it is not limited to HT-CLSM image data and can be applied to various domains.

CFD-DEM modeling of particle dissolution behavior in stirred tanks

A CFD-DEM particle dissolution model was established to study the particle dissolution process in a stirred tank. Firstly, the model's accuracy in simulating particle size and solute concentration was validated against experimental results, the errors were 6.13% and 12.5%, respectively. Secondly, the study delved into the mechanism of mass transfer dissolution from three dimensions: solute concentration distribution, particles spatial distribution, and energy dissipation rate of particles. It was found that the larger the concentration gradient, the better the dissolution of particles. As the dissolution progresses, the coupling force between the fluid and the particles weakens, and smaller particles are more easily suspended. Lastly, the dissolution behavior of particles at different rotation speeds was investigated. Stirring speed can significantly improve the dissolution rate of particles in the particle suspension and dispersion stage, but the difference of different rotational speeds on the dissolution rate becomes smaller in the particle circulation flow stage.

Evaluation of Individual and Crystal Population Dissolution Rates by Time-Resolved X-ray Microtomography.

The intrinsic dissolution rate (IDR) is an important parameter in pharmaceutical science that measures the rate at which a pure crystalline active pharmaceutical ingredient dissolves in the absence of diffusion limitations. Traditional IDR measurement techniques do not capture the complex interplay between particle morphology, fluid flow, and dissolution dynamics. The dissolution rate of individual particles can differ from the population average because of factors such as particle size, surface roughness, or exposure of individual crystal facets to the dissolution medium. The aim of this work was to apply time-resolved X-ray microtomography imaging and simultaneously measure the individual dissolution characteristics of a large population of crystalline particles placed in a packed bed perfused by the dissolution medium. Using NaCl crystals in three different size fractions as a model, time-resolved microtomography made it possible to visualize the dissolution process in a custom-built flow cell. Subsequent 3D image analysis was used to evaluate changes in the shape, size, and surface area of individual particles by tracking them as they are dissolved. Information about the particle population statistics and intrabatch variability provided a deeper insight into the dissolution process that can complement established IDR measurements.

Numerical study of solid-state oxygen control bypass performance and corrosion distribution in a LBE flow loop

Liquid lead–bismuth solid-state oxygen control technology is considered to be one of the effective means to inhibit corrosion of structural materials. The dissolution rate of PbO particles in the mass exchanger (MX) is a crucial factor influencing the effectiveness of solid-state oxygen control. To enhance the oxygen control efficiency of the MX, a PbO particle dissolution model based on the UPBEAT (Universal lead(Pb) bismuth(Bi) Eutectic Advanced Test loop) was established. This model aims to determine the impact of temperature, LBE flow rate, operating time, and initial oxygen concentration on the dissolution rate of PbO particles and the steady-state time in the MX. The obtained insights inform the design and operational aspects of the MX. Simultaneously, a loop corrosion precipitation model was developed to simulate loop corrosion in both oxygen-free and solid-state oxygen control states. While the corrosion precipitation distribution in the loop remains consistent between oxygen-free and oxygen-controlled states, solid-state oxygen control effectively enhances the corrosion resistance of the loop.

Dissolution mechanism and computational model for controlling dissolution rate of alumina particles in CaO–SiO2–Al2O3–MgO slag

In present study, a high-efficiency CaO–SiO2–Al2O3–MgO slag was designed to dissolve alumina particles, and the in situ observation for alumina particles dissolution by CSLM instrument equipped with color fast CCD camera was conducted, which broke through the limitations of the original CSLM equipment. The dynamic measurements showed that the dissolution behavior of alumina particles was controlled by diffusion. Moreover, the mechanism of dissolution of alumina particles was illustrated by combining SEM-EDS detection and thermodynamic calculations. It was found that there was an about 3 μm distinct interface layer when alumina particles were dissolved in slag, and the formation order of products of the interface layer was closely related to its thermodynamics. In addition, the apparent activation energy of reaction between Al2O3 and CaO was used to calculate the reaction time of alumina particles with different particle size, and the viscosity values of the all slags obtained by the Factsage 8.2 thermodynamic software and Stocks-Einstein theory were used to calculate the time required for diffusion of alumina particles with different particle sizes. Compared the total time of chemical reaction and the diffusion mass transfer, it is found that when the radius of alumina particles is greater than 2.5 μm, the dissolutions of alumina particles in all CaO–SiO2–Al2O3–MgO slag composition points are controlled by diffusion.

Preparation of glyburide nanocrystals with improved dissolution properties by dry-ball- and wet-bead- milling: Systematic comparison by experimental design of the performance of the two methods

The effectiveness of dry-ball and wet-bead nano-milling methods in producing nanocrystals of glyburide with increased dissolution rate has been compared. A full factorial design was applied to both methods to systematically evaluate the effect of the most critical factors (milling time, milling speed, ball/bead volume, drug amount) on the responses to be optimized (particle size and dissolution rate). Different experimental conditions were found to obtain the best results: the dry-method required to increase frequency and milling time and reduce ball volume and drug amount, while the wet-method to increase milling rate and drug amount and reduce bead volume and milling time. The results obtained under the respective optimal conditions evidenced a similar performance in nanocrystal production (120 and 180 nm for dry-ball and wet-bead milling, respectively) while a higher % dissolved at 10 min (28 vs 14 %) was found for the wet-method, principally ascribed to the presence, in this case, of the solubilizing polymer P188, added as stabilizer. Differently from the wet-method, the dry-method showed no direct relationship between particle size reduction and drug dissolution rate increase. Solid-state studies evidenced a role of the drug crystallinity loss, caused by the dry-milling, in affecting dissolution rate and proved the stability of the drug under both the milling processes.

Modeling of the Aqueous Solubility of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazine-3-carboxamide: From Micronization to Creation of Amorphous-Crystalline Composites with a Polymer.

N-butyl-N-methyl-1-phenylpyrrole[1,2-a] pyrazine-3-carboxamide (GML-3) is a potential candidate for combination drug therapy due to its anxiolytic and antidepressant activity. The anxiolytic activity of GML-3 is comparable to diazepam. The antidepressant activity of GML-3 is comparable to amitriptyline. GML-3 is an 18 kDa mitochondrial translocator protein (TSPO) ligand and is devoid of most of the side effects of diazepam, which makes the research on the creation of drugs based on it promising. However, its low water solubility and tendency to agglomerate prevented its release. This research aimed to study the effect of dry grinding, the rapid expansion of a supercritical solution (RESS), and the eutectic mixture (composite) of GML-3 with polyvinylpyrrolidone (PVP) on the particle size, dissolution rate, and lattice retention of GML-3. The use of supercritical CO2 in the RESS method was promising in terms of particle size reduction, resulting in a reduction in the particle size of GML-3 to 20-40 nm with a 430-fold increase in dissolution rate. However, in addition to particle size reduction after RESS, GML-3 began to show signs of a polymorphism phenomenon, which was also studied in this article. It was found that coarse grinding reduced particle size by a factor of 2 but did not significantly affect solubility or crystal structure. Co-milling with the polymer made it possible to level the effect of the appearance of a residual electrostatic charge on the particles, as in the case of grinding, and the increased solubility in the resulting mechanical mixtures of GML-3 with the polymer may also indicate the dissolving properties of polymers (an increase in 400-800 times). The best result in terms of GML-3 solubility was demonstrated by the resulting GML-3:PVP composite at a ratio of 1:4, which made it possible to achieve a solubility of about 80% active pharmaceutical ingredient (API) within an hour with an increase in the dissolution rate by 1600 times. Thus, the creation of composites is the most effective method for improving the solubility of GML-3, superior to micronization.

Activation Energy of Alumina Dissolution in FeO-Bearing Slags

The dissolution of Al2O3 non-metallic inclusions in slag containing FeO was investigated in this study. The slag system used in the experiments was a quaternary system of CaO-SiO2-Al2O3-FeO. The composition of the slag was studied by fixing the basicity (CaO/SiO2 ratio) to 1 and varying the FeO content to 10 and 20 wt%. In addition, the experimental temperature was varied to 1550 °C, 1575 °C, and 1600 °C to study the effect of temperature on the Al2O3 dissolution behavior. The experimental equipment used was a single hot thermocouple apparatus. The dissolution rate of Al2O3 particles increased linearly with increasing temperature and FeO content. In addition, the mass transfer activation energy of Al2O3 dissolution in FeO 10 wt% and FeO 20 wt% was calculated through an Arrhenius-type analysis. The obtained mass transfer activation energies were 159 and 189 kJ/mole, respectively.

Behavior and Kinetic Mechanism Analysis of Dissolution of Iron Ore Particles in HIsmelt Process Based on High-temperature Confocal Microscopy

In this study, high-temperature confocal microscopy (HTCM) was used to perform in situ observations of the dissolution of iron ore particles in slag at different temperatures. Moreover, the shrinking core model (SCM) is used to explain the kinetic mechanism of the dissolution of iron ore particles. The area of the undissolved fraction of iron ore particles was used to analyze the dissolution rate of iron ore particles. The results show that the kinetic mechanism of dissolution of iron ore particles can be well explained by the SCM. The dissolution of iron ore particles is controlled by the diffusion of iron ore fractions in the boundary layer. The dissolution temperature, the concentration difference of iron ore fraction at the two ends of the boundary layer, and the initial particle size of iron ore particles affect the dissolution rate of iron ore particles. The dissolution rate constant was fitted by introducing a dissolution mechanism. The activation energy of iron ore dissolved in the CaO–SiO2–MgO–Al2O3–FeO slag system is 679.13 kJ/mol. The equation for the dissolution rate constant of iron ore in HIsmelt slag is summarized.

Formulation study of duloxetine hydrochloride enteric-coated tablets

During storage, duloxetine hydrochloride may have an unexpected cross reaction with enteric coated acrylic resin, which may affect the product quality. Solve the problem of cross-reaction between the Duloxetine enteric-coated tablets core and coated enteric materials and improve the quality of the products. Duloxetine enteric-coated tablets’ core formulation and isolation layer prescription were designed and compared with duloxetine enteric-coated tablets sold on the market. Then, we measured the dissolution rate, content, and releasing rate of prepared duloxetine enteric-coated tablets. In the formulation of tablets core, prescription 3 had advantages in particle mobility, disintegration time, and dissolution rate. Prescription 5 was stable during the coating process, and the dissolution residue in the cup was relatively good, showing obvious dissolution advantages. Thus, prescription 5 was selected as the isolation layer prescription. The most suitable adhesive for the preparation of Duloxetine hydrochloride enteric-coated tablets was povione K30 dissolved in ethanol solution with 1/2 of the prescription amount. When 1.3 g colloidal silica was added to the prescription and the dosage of magnesium stearate was 1.48 g, the dissolution rate of the drug could be relatively improved. The ratio of sucrose and talc was 138/8.7, which could effectively configure the coating solution with a solid content of 15–20% to make the coating smooth.

Assessing the effect of moderately increasing medium viscosity on the intrinsic dissolution rate and diffusion coefficient of ibuprofen particles

This study investigated the effects of moderately increasing medium viscosity through two viscosity enhancing agents (VEA) (HPMC and sucrose) on the intrinsic dissolution of a BCS class II drug (ibuprofen). The differences in intrinsic dissolution were characterized through the estimation of a diffusion coefficient (D) of ibuprofen in different media with the Levich equation. Increasing viscosity decreased the intrinsic dissolution rate of ibuprofen with both VEAs. The calculated D from intrinsic dissolution data overestimated the experimental value, but the results suggest that intrinsic dissolution could be used as a tool to estimate a relative change in D in different viscosities. 

The effect of FexO content on dissolution behavior of an alumina inclusion in CaO–Al2O3–SiO2–FexO slag by a single hot thermocouple technique

The dissolution behavior between CaO–SiO2–Al2O3–FexO slag and Al2O3 particles was studied by the Single Hot Thermocouple technique (SHTT) at 1550 °C. The FexO content in the slag with a fixed basicity (CaO/SiO2 ratio) of 1 varied from 10 to 30%. The dissolution behavior between slag with transition metal oxides and Al2O3 particles was investigated through a new research method of the Single Hot Thermocouple Technique (SHTT), which is a fast quenching method. The conditions under which the SHTT is possible were derived as a stability diagram. The results of the experiment revealed that the dissolution rate of the Al2O3 particles increased with an increasing FexO content in the range of 0–20% FexO content of slag, but the dissolution rate of Al2O3 particles did not increase when the FexO content was 30%. It was found that the Ca(Al, Fe)12O19 phase was formed in the slag with 30% FexO content.

Determination of Alteration in Micromeritic Properties of a Solid Dispersion: Brunauer-Emmett-Teller Based Adsorption and Other Structured Approaches.

The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3rd generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m2/g and 8.2757 m2/g, respectively.Graphical

Pembuatan dan Karakterisasi Self Emulsifying Drug Delivery Systems(SEDDS) Ibuprofen Secara Oral

Self emulsifying drug delivery systems (SEDDS) dikembangkan sebagai metode untuk meningkatkan kelarutan obat lipofilik seperti ibuprofen, serta untuk meningkatkan absorpsi dan laju disolusi obat. Oleh karena itu penelitian ini bertujuan untuk mengembangkan formulasi SEDDS ibuprofen yang memenuhi syarat secara farmasetik dan meningkatkan bioavailabilitas ibuprofen. Formula SEDDS diperoleh dari uji kelarutan ibuprofen dan optimasi formula pada berbagai konsentrasi minyak, surfaktan dan kosurfaktan. Asam oleat, cremophor RH 40 dan propilenglikol masing-masing terpilih sebagai minyak, surfaktan dan kosurfaktan dengan perbandingan fase minyak : (surfaktan + kosurfaktan) 1:9 dan pebandingan surfaktan : kosurfaktan (3:2). Formula SEDDS optimum dievaluasi meliputi pengukuran persen transmitan, pengujian dispersibilitas, pengujian robustness, pengujian stabilitas (sentrifugasi, heating cooling cycle, freeze thaw cycle), penentuan ukuran partikel dan uji laju disolusi. Formula SEDDS ibuprofen terbaik memenuhi persyaratan persen transmitan (99,7% ± 0,872), waktu dispersibilitas (41,48 detik ± 1,3), stabil pada pengujian robustness, tidak terjadi pemisahan fasa pada pengujian stabilitas, serta memiliki ukuran globul dalam kisaran mikrometer yaitu 114,7 ± 0,692 nm. Hasil uji laju disolusi in vitro pada menit ke-10 menunjukkan bahwa sediaan SEDDS ibuprofen lebih tinggi dibandingkan dengan serbuk ibuprofen murni, yaitu masing-masing sebesar 90,04 ± 1,764% dan 59,30 ± 1,638%.

Effect of Particulate Properties of Inhaled Dry Powder Formulation on Bioavailability, Dissolution Rate of Drug Particles and Rate of Drug Removal from the Body

Introduction: The use of pulmonary drug delivery as a non-invasive drug delivery system for the systemic treatment of diseases as well as the topical treatment of respiratory diseases is increasing. Among the various inhaled formulations, inhaled dry powders show advantages over the other forms of inhaled medicines due to high stability, bioavailability and ease of use. The effect of particle properties on the rate of drug delivery to the lungs in inhaled dry powders has been investigated in previous papers.
 Conclusion: Since the physicochemical properties of particles of dry powder inhalation formulations such as particle size, surface and particle shape, as well as the electrical charge of the particles play a decisive role in drug pharmacokinetics, in the present review article we intended to discuss the effect of these parameters of inhaled dry powder formulations on bioavailability, dissolution rate of drug particles and the rate of drug clearance from the body.

Study of Structural and Optical Properties of Electrodeposited Silicon Films on Graphite Substrates.

Silicon (Si) films were deposited on low-cost graphite substrates by the electrochemical reduction of silicon dioxide nanoparticles (nano-SiO2) in calcium chloride (CaCl2), melted at 855 °C. Cyclic voltammetry (CV) was used to analyze the electrochemical reduction mechanism of SiO2 to form Si deposits on the graphite substrate. X-ray diffraction (XRD) along with Raman and photoluminescence (PL) results show that the crystallinity of the electrodeposited Si-films was improved with an increase of the applied reduction potential during the electrochemical process. Scanning electron microscopy (SEM) reveals that the size, shape, and morphology of the Si-layers can be controlled from Si nanowires to the microcrystalline Si particles by controlling the reduction potentials. In addition, the morphology of the obtained Si-layers seems to be correlated with both the substrate materials and particle size of the feed materials. Thus, the difference in the electron transfer rate at substrate/nano-SiO2 interface due to different applied reduction potentials along with the dissolution rate of SiO2 particles during the electrochemical reduction process were found to be crucial in determining the microstructural properties of the Si-films.

Mass transfer intensification by means of resonance oscillations in a pulsation apparatus with a central tube with and without nozzles

An experimental study of resonance and non-resonance oscillations in a pulsating apparatus with a central tube was performed. Pulsating apparatus in two configurations was thoroughly investigated in the following way: (i) pulsating resonance apparatus with central tube, without nozzles and (ii) pulsating resonance apparatus with central tube, an additional tube, and nozzles. The following parameters were investigated as criteria for the onset of resonance: the liquid surface oscillations amplitude, the gas pressure oscillations amplitude in a gas-filled elastic element, the solid particles dissolution rate. A comparative analysis showed that the resonance frequencies, determined by the maximum amplitude of the liquid surface oscillations, by the gas pressure fluctuations and the dissolution rate of solid particles, are in good agreement with each other and with the theoretical value. The pressure pulsations were found as an easy and reliable for resonance identification. The dissolution rate of KOH particles increases up to 4–6 times at resonance frequency. At the same energy dissipation rate possesses approximately 10 times larger values of the liquid-solid mass transfer coefficient compared to the stirred tanks. With a decrease in the volume of a gas-filled elastic element, the amplitude of the oscillations at resonance increases, which is consistent with theory.