Disintegration Mechanisms Research Articles

Exploring the performance-controlling tablet disintegration mechanisms for direct compression formulations

The design and manufacture of tablets is a challenging process due to the complex interrelationships between raw material properties, the manufacturing settings and the tablet properties. An important factor in formulation and process design is the fact that raw material and tablet properties drive the disintegration and dissolution performance of the final drug product. This study aimed to identify the mechanisms which control tablet disintegration for 16 different immediate-release placebo formulations based on raw material and tablet properties. Each formulation consisted of two fillers (47% each), one disintegrant and a lubricant. Tablets were manufactured by direct compression using four different combinations of the fillers microcrystalline cellulose (MCC), mannitol, lactose and dibasic calcium phosphate anhydrous (DCPA). The disintegration mechanism was primarily driven by the filler combination, where MCC/lactose tablets were identified as wettability controlled, MCC/mannitol tablets as dissolution controlled and DCPA-based tablets (MCC/DCPA and lactose/DCPA) as swelling controlled. A change of 2% in porosity for the wettability controlled tablets (MCC/lactose) caused a significant acceleration of the disintegration process (77% reduction of disintegration time), whereas for swelling controlled tablets (MCC/DCPA) the same porosity change did not considerably impact the disintegration process (3% change in disintegration time). By classifying these formulations, critical formulation and manufacturing properties can be identified to allow tablet performance to be optimised.

Ion Track Etching Revisited: IV. Thermal annealing of fresh swift heavy ion-irradiated PET in different environments

ABSTRACT Many studies have already been performed on the thermal annealing of fresh and aged swift heavy ion-irradiated polymers in a vacuum. In this paper we examine the influence of different environments on annealing behaviour. The basic tool for this study is current/voltage spectroscopy with the alternating voltage applied across the etched tracks. In previous work of this series it was shown for etching of previously annealed aged swift heavy ion-irradiated polyethylene terephthalate foils in dry air that at ∼ 50°C, a dip overlapped the expected Arrhenius correlation in the Arrhenius plot of the etchant breakthrough times. We had attributed that dip tentatively to the etching of the swift heavy ion track core material, as the latter had been subjected to extremely high radiation-damage and thus differs strongly in its composition from pristine bulk material. Repetition of this experiment under different annealing environments enables us to draw conclusions about the competition between the different polymeric disintegration and healing mechanisms in swift heavy ion tracks. These results should be useful for better estimation of the polymeric durability in different environments. First tests with polyimide reveals that a similar dip structure also shows up here, indicating that this finding may be a general effect for annealing of ion-irradiated polymers.

Nanoscale disintegration kinetics of mesoglobules in aqueous poly(N-isopropylacrylamide) solutions revealed by small-angle neutron scattering and pressure jumps.

Identification and control of the disintegration mechanism of polymer nanoparticles are essential for applications in transport and release including polymer delivery systems. Structural changes during the disintegration of poly(N-isopropylacrylamide) (PNIPAM) mesoglobules in aqueous solution are studied in situ and in real time using kinetic small-angle neutron scattering with a time resolution of 50 ms. Simultaneously length scales between 1 and 100 nm are resolved. By initiating phase separation through fast pressure jumps across the coexistence line, 3 wt% PNIPAM solutions are rapidly brought into the one-phase state. Starting at the same temperature (35.1 °C) and pressure (17 MPa) the target pressure is varied over the range 25-48 MPa, allowing to systematically alter the osmotic pressure of the solvent within the mesoglobules. Initially, the mesoglobules have a radius of gyration of about 80 nm and contain a small amount of water. Two disintegration mechanisms are identified: (i) for target pressures close to the coexistence line, single polymers are released from the surface of the mesoglobules, and the mesoglobules decrease in size, which takes ∼30 s. (ii) For target pressures more distant from the coexistence line, the mesoglobules are swollen by water, and subsequently the chains become more and more loosely associated. In this case, disintegration proceeds within less than 10 s, controlled by the osmotic pressure of the solvent.

Optimal Design, Characterization and Preliminary Safety Evaluation of an Edible Orodispersible Formulation for Pediatric Tuberculosis Pharmacotherapy.

The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug–excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.

Fenomen brexitu w rozważaniach szkoły prawa i ekonomii

The Phenomenon of Brexit in the Considerations of the School of Law and Economics The article addresses the issue of Brexit in the context of economic analysis of law using a qualitative method, namely the textual analysis of selected papers devoted to both the process of secession of Great Britain from the European Union and the aforementioned research school. The hypothesis of this work is as follows: economic analysis of law reveals limited applicability to the exegesis of the Community disintegration mechanisms, including Brexit, which is one of the symptoms of these processes. According to the author, it reveals certain shortcomings in the research procedures regarding the phenomenon of EU decomposition, although, on the other hand, some of its components still remain valid.

Splashing of fuel drops impacting on heated solid surfaces

Liquid drop impact on dry, solid surfaces has been studied to elucidate the role of control parameters, such as drop size, impact velocity, liquid properties, surface roughness, and wettability, on the mechanism of splashing phenomenon. It has been shown more recently that ambient gas plays a pivotal role in initiating the disintegration mechanisms leading to the ejection of secondary droplets from an impacting drop. Through systematic experiments, the role of target surface temperature in altering the morphology of a splash outcome of impacting fuel drops is investigated in the present work. It is observed that at elevated surface temperatures, the heated air film present very close to the hot surface suppresses splashing and consequently raises the splash threshold Weber number of the impacting fuel drop. For a given Weber number, the morphology of the impacting drop shifts from splashing to spreading with a rise in the surface temperature through an intermediate transition regime, characterized by the tendency of the liquid sheet to recontact the drop lamella without ejecting any secondary droplets. The experimental observations are compared with theoretical model predictions reported in the literature, and fair agreement is found in terms of both the observed splash suppression and the underlying mechanisms that govern the identified morphological regimes.

Mineral raw material disintegration mechanisms in ball mills and distribution of grinding energy between sequential stages

The studies were carried out under the contracts with the company CJSC “Zapolyarny filial Norilsk Nickel” (Russian Federation), Zangezur Mining and Processing Plant (Republic of Armenia) and Almalyk Mining and Metallurgical Plant (Republic of Uzbekistan). The authors are grateful to Prof. Ciril O’Connor, President of the International Minerals Processing Congress, Center for Minerals Research, University of Cape Town (South Africa), Academician of RAS, Prof. V.A. Chanturia, for the comprehensive support of the scientific research related to the intensification of the processes associated with ore preparation for concentration. The authors extend their thanks to NPK “Mekhanobr-tekhnika” and LLC “Resurs” for the provided base and assistance in organizing experimental studies, as well as to all employees of the above mentioned organizations, who had participated in implementation of the studies at enterprises of the industry.

Brexit a liberalna teoria stosunków międzynarodowych.

Hereby paper is dedicated to the issue of Brexit in the context of liberal theory of international relations, mainly by adoption of the qualitative method of textual examination of selected works, devoted to the abovementioned paradigm. The hypothesis of this article is a statement that liberal approach has a limited applicability to description of community disintegration mechanisms, including Brexit as their unquestionable syndrome. Existing theories of European integration, of which liberalism is one of the most influential theoretical schemes, reveal several malfunctions in exploration of Union’s decomposition processes, however, on the other hand, some of their specific components still remain valid. The above issue exposes a demand for investigating new tools and researching methods to scrutinize current trends in the European Union that would allow to review the present state of this organization in a more adequate manner.

Quantifying contributions of slaking and mechanical breakdown of soil aggregates to splash erosion for different soils from the Loess plateau of China

The information of aggregate disintegration mechanisms during splash erosion is scant. This study was conducted to quantify contributions of the mechanisms of aggregate disintegration to splash erosion. Six soils with five soil textures were used. Soil aggregate stability was determined by the Le Bissonnais (LB) method. Deionized water was used to simulate the combined effect of slaking and mechanical disaggregation, while ethanol was used to estimate the sole contribution of the mechanical breakdown. Simulated rainfall with intensity of 60 mm h−1 was applied at five fall heights (0.5 m, 1 m, 1.5 m, 2 m and 2.5 m) to achieve different levels of rainfall kinetic energy. The results indicated that slaking caused the most severe aggregate breakdown, and followed by mechanical breakdown, while chemical dispersion in slow wetting with deionized water was the weakest breakdown mechanism. The splash erosion rates due to the effects of slaking and mechanical breakdown increased with an increase in rainfall kinetic energy. The contributions of the slaking (mechanical breakdown) to splash erosion decreased (increased) as rainfall kinetic energy increased. The contribution of mechanical breakdown had a power function relation with rainfall kinetic energy, and had the most significant correlation with RSI (relative slaking index)/RMI (relative mechanical breakdown index). A power and a linear function could be used to describe the relationships between the contributions of mechanical breakdown with rainfall kinetic energy and RSI/RMI, respectively, which could be used to estimate the contribution of mechanical breakdown. The results of this research would be helpful to improving the soil erosion prediction models.

Spectrophotometric analysis of disintegration mechanisms (abrasion and crushing) of agglomerates during the disc granulation of dolomite

The analysis of mechanisms which affect the formation of agglomerates and determine the granulation process in a broad sense encounters difficulties related to the many ways of the formation of granules. The aim of the study was to perform a qualitative and quantitative analysis of granulation mechanisms with special reference to agglomerates’ disintegration in the disc granulation process. This paper contains an analysis of disintegration mechanisms (abrasion and crushing) of agglomerates during the disc granulation of dolomite. The analysis of the mechanisms taking place during the process concerns the granulation stage after wetting. During the research, each time after the wetting stage, the size fraction 10–12.5 mm was substituted with an analogous fraction wetted by means of an aqueous solution of a coloring agent and the process was continued. After the specified time of granulation, the obtained product was sieved through laboratory sieves and then the content of the provided coloring agent in different size fractions was analyzed by means of a spectrophotometer. Measuring the absorbance of the analyzed samples and granulometric composition of the bed, the level and cause of the migration of material of the tested fraction into other size classes were determined, and at the same time, the occurring granulation mechanisms were analyzed. The proposed model and measurement method consisting of determining the absorbance of the tested granulometric fraction enable the qualitative and quantitative analysis of granulation mechanisms are encountered during the carrying-out of the process after wetting the bed.

Metal Ion-Loaded Nanofibre Matrices for Calcification Inhibition in Polyurethane Implants.

Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg2+ ions in human body, and the anti-calcification effect of Fe3+ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe3+ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg2+ ions are more promising candidates than Fe3+ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix.

Chitin’s Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure “Py” shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation.

동축형 다공성재 분사기의 분열 메커니즘

동축형 다공성재 분사기에서는 기체가 분사기 중심을 지나는 액체 제트 주위를 둘러싼 다공성재를 통해 액체 제트를 향해 분사된다. 분사 방법의 차이로 인한 전단동축 분사기와 동축형 다공성재 분사기의 분열 메커니즘 차이를 살펴보기 위해, 전단동축 분사기와 동축형 다공성재 분사기를 사용하여 수류시험과 2-D 축대칭 수치해석을 진행하였다. 같은 유량조건에서의 가시화 이미지와 분무 평균입경을 비교하였으며, 수치해석을 통해 분사기 내부에서의 속도 분포가 액체 제트에 어떤 영향을 끼치는지 고찰하였다. 결과적으로, 기체의 유량이 늘어날수록 분사기 내부 속도가 낮음에도 동축형 다공성재 분사기의 미립화 및 혼합 성능이 전단동축 분사기에 비해 유리함을 확인할 수 있었다. In a coaxial porous injector, a gas propellant is injected through the porous cylinder surface to the liquid jet which is encircled by a porous cylinder. In this study, to observe the differences in disintegration mechanisms between a shear coaxial injector and a coaxial porous injector, cold-flow tests and 2-D axisymmetric numerical analysis have been carried out. The shadowgraph images and Sauter mean diameters were compared in similar experimental conditions, and the effects of velocity distributions at the inner injector region on the disintegration of liquid jet were investigated through the numerical calculations. As a result, in high air mass flow rate condition, the disintegration performance of coaxial porous injector is better than shear coaxial injector, in spite of a lower velocity at the inner injector region.

Evidence of Meteoroid Fragmentation in Specular Trail Echoes Observed Using Gadanki MST Radar

Meteoroids are responsible for deposition of thousands of kilograms of annual mass flux in the Earth’s upper atmosphere but the disintegration mechanisms of these bodies, and hence their composition, still remains a subject of debate in the meteor radar community. The role and significance of fragmentation as a meteoroid disintegration mechanism has been of particular interest in the past few years but in contrast to the head echoes, relatively little work has been done to study the effect and extent of fragmentation on trail echoes observed by the high power large aperture radars. Using the 53 MHz Gadanki MST radar, we present examples of radar meteor trails whose evolution cannot be explained with just the aid of classical meteor ablation theory. These examples are analyzed and discussed on a case-by-case basis and it is reported that the evolution of these trails can be explained with the help of fragmentation. This study will form the basis for future modeling efforts of fragmenting meteor trails and has important implications on the form in which the meteoroid mass is deposited in the upper atmosphere.

Advances in the theoretical and molecular simulation studies of the ion chemistry in droplets

We review recent theoretical and computational advances in the understanding of ejection mechanisms of solvated ions and macromolecular ions (macroions) from highly charged nanodrops. The excess charge is carried by simple ions or macroions. On the one hand, the principal factors that lead to the instability of a droplet due to its high charge are captured by fundamental theories. These theories consider the competition between the electrostatic interactions between ions of the same sign that tend to fragment the droplet and the surface tension that tends to keep the droplet connected. On the other hand, a detailed description of the molecular mechanism of the fragmentation in these complex systems has still not been developed. Development of a comprehensive model for the droplet fragmentation is further complicated by chemical modifications of the macromolecule by binding to alkali ions, divalent ions or protons in a constantly changing droplet environment. We describe our major findings in understanding the disintegration mechanisms of charged droplets. For droplets containing simple ions, we utilise computational methodology for activated processes to describe the ejection of solvated ions. We found that the transition state involves bottle-neck configurations where the ions leave a droplet by shape fluctuations that are similar to “Taylor” cones or string formations of the solvent. In the presence of macromolecular ions, due to the connectivity of the charge along the macromolecular backbone, droplets take different shapes from those that contain simple ions. By using molecular dynamics simulations we classified these droplet states as contiguous extrusion of the macroion from a droplet, drying-out, star-like formation of solvent surrounding a macroion and pearl formation along the macromolecular chain. Quantitative analysis of each of the droplet states calls for its own theoretical description to generalise the simulation findings. Using a combination of analytical theory and molecular simulations we proposed a theoretical model for the contiguous extrusion of a macromolecule from a droplet.

Disintegration of periodate–chlorite oxidized hardwood pulp fibres to cellulose microfibrils: kinetics and charge threshold

Periodate–chlorite oxidized bleached hardwood kraft pulp fibre samples with six levels of charge densities ranging from 0.5 to 1.8 mmol/g were gradually disintegrated to microfibrils using a high-shear homogenizer. The disintegration kinetics and mechanisms were studied by a flow fractionation method, and the properties of the resulting particles were determined using low shear viscosity and transmittance measurements. The particles formed during the disintegration were visualized with a charge-coupled device camera and by field-emission scanning electron microscopy. The result showed that cellulose fibres with a low charge density disintegrated at a low rate and produced ragged fibres and bunches of microfibrils via bursting of the fibre walls, whereas those with a higher charge density broke down at a high rate and microfibrils were formed through swelling and the creation of balloon structures. A carboxyl content of 1.2 mmol/g was found to be the threshold value for the efficient formation of high aspect ratio microfibrils and also for the change in the disintegration mechanism in the high-shear homogenizer.

Systematic classification of tablet disintegrants by water uptake and force development kinetics.

Water uptake and force development of disintegrating tablets provide a high degree of information about the disintegration mechanisms and process itself. An apparatus for the simultaneous measurement of water uptake and force development of tablets is presented, and the gathered data are analysed. Flat faced, 10 mm, dibasic calcium phosphate tablets containing 2% disintegrant are investigated with the newly constructed apparatus. The force is determined with a texture analyser, whereas the water uptake is recorded by a balance. Different measurement regimes are compared with each other. Measured curves are analysed according to their shape and fitted with a modified Hill equation. Known disintegration mechanisms can be confirmed with the newly constructed apparatus - swelling for sodium starch glycolate and croscarmellose sodium, and shape recovery for crospovidone disintegrants. Different brands of polacrilin potassium act by different mechanisms. All curves could be fitted successfully with a modified Hill equation. A novel classification to facilitate the appropriate disintegrant selection is presented on basis of the fit parameters. The new apparatus allows the acquisition of water uptake and force data simultaneously. Parameters calculated with the modified Hill equation provide a simple way to classify disintegrants according to their behaviour.

Formulasi dan Evaluasi Tablet Alprazolam 1 mg

Alprazolam is benzodiazepines drug which used to manage short-term anxiety disorder, also used for the treatment of panic disorder, with or without agographobia. Many factors can affect drug dissolution rates from tablets, hence possibly drug bioavailability- including the crystal size of the drug, tablet disintegration mechanisms and rates, the method of granulation, type and amount of granulating agent employed, type, amount and method of incorporation of disintegrants and lubricants and other formulation and processing factors. The aim of the study was to prepare and evaluate alprazolam tablets with dosage strengths 1 mg, with wet granulation method, as an adjuvant used: corn starch and lactosa sebagai filler, sodium lauril sulfat as solubilizer, sodium starch glycolat as desintegrant, Erytrocin CI 45430 as colloring, polivinyl pirolidon K 30 as binder with variatrion concentration, ethanol 95% as wetting agent, talc, silicon dioksida coloidal and magnesium stearat as glidant and antiadherent, test for the granule are particle distribution, water content, angle of repose, bulk density, taped density, apparent density (compressibility), and test for the tablet dosage are description of tablet, wight uniformity, hardness, desintegration time, content uniformity, disolution, for the selected formula tested the comparison of disolution and bioequivalence to 1 mg Alprazolam tablet innovator , the results obtained, that the tablet alprazolam 1 mg, are meet the requirements. Keywords : Alprazolam, bioequivalence test, dissolution comparison test

Disintegration mechanisms of charged nanodroplets: novel systems for applying methods of activated processes

We review recent advances in the understanding of ejection mechanisms of solvated ions and charged macromolecules from highly charged nanodroplets. While the physical basis for the instability leading to droplet fragmentation is relatively well understood, a description of molecular mechanism of the fragmentation in complex systems is still missing. Development of a comprehensive model for the droplet fragmentation is further complicated by chemical modifications of the charged macromolecules (macroions) in a changing droplet environment. We highlight several different molecular simulation techniques used to study fragmentation of charged droplets with different solutes. Ejection of simple ions is analysed using theory of activated processes and transfer reaction coordinate (TRC). The TRC was shown to adequately represent complex rearrangement of solvent molecules in the course of evaporation. The critical value of the square of the charge to volume ratio for spontaneous ejection of simple solvated ions from aqueous droplets is found to be very close to that predicted by Rayleigh's model. On the contrary, the presence of macromolecules adds a level of complexity into the system where the charge-induced instabilities cannot be described by a conventional theory such as Rayleigh or ion-evaporation mechanism. Additional charge–charge interactions between charged sites on a macromolecule dramatically change the macroion ejection mechanism. Molecular dynamics simulations reveal a number of distinct scenarios: contiguous extrusion, drying-out, star-like formation of solvent surrounding a macroion and pearl formation along the macromolecular chain.

CARACTERIZAÇÃO METALÚRGICA DO PRODUTO GRANULADO DE MANGANÊS DE URUCUM

This work proposes a study about important metallurgic parameters of Urucum manganese lump ore, which are: cold and hot particle disintegration mechanisms, heat decompositions and the pre-reduction behavior. A tone of the studied ore was received and representative samples were collected for characterization procedures. Aiming to study ore heat decompositions, it was proposed a quantitative index named Evolution of Heat Decomposition (EHD). Using this index, the chemical and mineralogical characterization data, it was possible to determine the main reactions of mineral decomposition. Two quantitative parameters were proposed to describe the ore solid state reduction; these indexes were named Pre-reduction Efficiency (PE) and Pre-reduction Instantaneous Rate (PIR). Applying these parameters it was possible to conclude that Urucum lump ore has a great pre-reduction behavior. The characterization of particle disintegration was performed using three new indexes for manganese ores, which were: Cold Disintegration Index (CDI), Decrepitation Index (DI) and Hot Disintegration Index (HDI). These indexes showed that the studied ore did not presents significant cold particle disintegration, but it is susceptive to decrepitation and hot particle disintegration