Statistical comparison of high-shear versus low-shear granulation using a common formulation

Experimental combinations from the ranges assigned to the independent factors were studied using both a low-shear (planetary) mixer and a high-shear mixer for granulation. The independent factors studied were X₁ calcium phosphate/mannitol ratio, X₂ pregelatinized starch, X₃ magnesium stearate, X₄ mixer type, and X₅ compression pressure. To optimize the tablet properties fully, the experimental range was varied from -2 to +2 experimental units, with the exception of X₄, which was assigned -1 for the planetary mixer and +1 for the high-shear mixer. Drug dissolution did not seem to be affected by mixer type, but tablet hardness was affected by mixer type.     

An extended cell-average technique for a multi-dimensional population balance of granulation describing aggregation and breakage

This paper focuses on obtaining the numerical solution to a three-dimensional population balance model (PBM) of granulation using the cell-average technique first proposed by [22]. Conventionally, linear grids are used for the solution of PBMs, but the ability to incorporate non-linear grids would be more advantageous given that a larger size range can be covered using fewer number of grids, thus reducing computational overhead. Furthermore, the use of linear representation of grids in PBMs to represent industrial granulation processes that span a wide granule size range is computationally prohibitive and results show that a non-linear grid representation is computationally more efficient with comparable accuracy. Parallelization of the PBM via a multi-core strategy has also been incorporated in order to reduce the simulation time of the model. Incorporating the cell average technique along with parallelization of the overall model lends credence to the overall use of the model for effective granulation process design and analysis.     

Use of experimental designs to optimize fluidized bed granulation of maltodextrin

The goal of this study was to use the experimental design approach in order to determine which process parameters are the most influent to granules properties. The agglomeration process was performed with a fluidized bed processor equipped with a top-spray tilted nozzle. The granules were obtained by binding fluidized particles of maltodextrin (DE 12) with an aqueous solution of maltodextrin. The variables considered in the experimental design were fluidization air flow rate, drying air temperature, spraying pressure and binder flow rate. The physical properties of the granules were evaluated in terms of granule size, particle size distribution, dissolution time and flowability. Moreover, the amount of binder for each experiment was noted. The statistical analysis performed with Statgraphics® Centurion version XVI software indicated that the best operating conditions were found for low fluidization air flow rate, high drying air temperature, high spraying pressure and high binder flow rate. The study also revealed the difficult task of acquiring all the optimum properties at the same time.     

Modelling effects of processing parameters on granule porosity in high-shear granulation

When trying to meet final product specifications for porosity of granules made using high-shear granulation there are many choices for the formulation recipe and processing conditions. This paper presents the concept of a Critical Packing State of the primary particles forming a granule and the associated Limiting Binder Ratio, which allows granule consolidation to be modelled. The effect on consolidation of varying the following processing parameters is explained: Mixing intensity, mixing time and binder addition method. The effects of varying the following aspects of the formulation recipe are explained: Primary particle type, shape and size distribution, binder type and binder: solid ratio.     

Influence of process variable and physicochemical properties on the granulation mechanism of mannitol in a fluid bed top spray granulator

This study investigated the influence of specific process variables, including the hydroxypropyl cellulose (HPC) binder solution atomization, on the fluidized bed top spray granulation of mannitol. Special attention was given to the relationship between wetting and the granule growth profile. The atomization of the HPC binder solution using a binary nozzle arrangement produced droplets of decreasing size as the atomization pressure was increased, while changes in the spray rate had little effect on the mean droplet size. Increasing the HPC binder concentration from 2 to 8% w/w increased the binder droplet size and was most likely attributed to higher solution viscosity. The top spray granulation of mannitol showed induction type growth behavior. Process conditions like high spray rate, low fluidizing air velocity and binder solution concentration that promote the availability of HPC binder solution at the surface of the particles appeared to be key in enhancing nucleation and growth of the granules. Increasing the bed moisture level, up to a certain value, reduced the contribution of attrition to the overall growth profile of the granule and, more significantly, produced less granule breakage on drying. It was observed that the mean granule size could be reduced as much as 40% between the end of granulation and the end of drying for lower initial bed moisture level despite a shorter drying phase. High atomization pressure, especially when maintained during the drying phase, contributed substantially to granule breakage.     

Using experimental design to optimize the process parameters in fluidized bed granulation

In this study many parameters were screened for a small-scale granulation process for their effect on the yield of granules between 75 and 500 μm and the geometrical granule mean size (d50). First a Plackett-Burman design was applied to screen the inlet air temperature, the inlet flow rate, the spray rate, the nozzle air pressure, the nozzle spray diameter, and the nozzle position. The Plackett-Burman design showed that the key process parameters were the inlet flow rate and the spray rate and probably also the inlet air temperature. Afterward a fractional factorial design (2^5-2) was applied to screen the remaining parameters plus the nozzle aircap position and the spraying time interval. The fractional factorial design showed that the nozzle air pressure was also important. As the target values for the granule yield (between 75 and 500 μm) and the geometric mean granule size (between 300 and 500 μm) were reached during the screening experiments, further optimization was not considered necessary.     

Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors

Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (q(max)) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).     

90m高造粒塔控制爆破拆除

造粒塔高径比大且剪力墙结构楼梯间位于倒塌中心线上,为避免塔体爆而不倒,使其安全顺利倒塌,通过提高爆破切口高度,对部分塔体采取适当的预处理,并根据试爆效果确定合理的爆破参数,采用孔内延时、孔外接力的复式闭合双回路延时起爆网路,在倒塌区域铺设缓冲垫层、周边开挖减振沟以及对被保护物采取近体防护等相应措施,确保了造粒塔按照方案设计方向倒塌,取得了良好的爆破效果,达到了安全、精细爆破拆除的目的。可为同类爆破工程提供参考。     

90m高造粒塔控制爆破拆除

造粒塔高径比大且剪力墙结构楼梯间位于倒塌中心线上,为避免塔体爆而不倒,使其安全顺利倒塌,通过提高爆破切口高度,对部分塔体采取适当的预处理,并根据试爆效果确定合理的爆破参数,采用孔内延时、孔外接力的复式闭合双回路延时起爆网路,在倒塌区域铺设缓冲垫层、周边开挖减振沟以及对被保护物采取近体防护等相应措施,确保了造粒塔按照方案设计方向倒塌,取得了良好的爆破效果,达到了安全、精细爆破拆除的目的。可为同类爆破工程提供参考。     

Analytical methods for thorium determination: a journey from conventional methods to novel applications

Thorium may be determined using a variety of analytical methods. These may be based on chemical or physical principles or may make use of the radioactive decay of the individual thorium isotopes. The method to be used for a certain analytical purpose is selected as a function of the matrix of the sample and of the concentration of thorium. The present paper describes different methodologies, their range of application and discusses selected results. The methods described cover a concentration range of more than twelve orders of magnitude, i.e. from concentrated solutions to micrometre-sized particles. Emphasis is given to active radiometric techniques, chemical and instrumental analysis.     

Evaluation of migrational behaviour of plastic food-contact materials: a comparison of methods

PVC was selected as the plastic to be used in these experiments. The study was performed in two different modes, representing static and dynamic conditions. The latter represented transport simulation and this was one of our major objectives: to evaluate the effects of vibrations on migration phenomena. Our assessment of UV and GC techniques revealed that both are valuable procedures depending on the requirements of the analysis. The results obtained by the UV methodology clearly show that the change of migration per unit of time in the case of dynamic conditions is higher when compared into static conditions by a factor of 21.5. Nearly the same relationship came to light in the GC analysis of the specific migration of 2-ethylhexanoic acid into water. Copyright © 1998 John Wiley & Sons, Ltd.     

Evaluation and comparison of estimation methods for failure rates and probabilities

An updated parametric robust empirical Bayes (PREB) estimation methodology is presented as an alternative to several two-stage Bayesian methods used to assimilate failure data from multiple units or plants. PREB is based on prior-moment matching and avoids multi-dimensional numerical integrations. The PREB method is presented for failure-truncated and time-truncated data. Erlangian and Poisson likelihoods with gamma prior are used for failure rate estimation, and Binomial data with beta prior are used for failure probability per demand estimation. Combined models and assessment uncertainties are accounted for. One objective is to compare several methods with numerical examples and show that PREB works as well if not better than the alternative more complex methods, especially in demanding problems of small samples, identical data and zero failures. False claims and misconceptions are straightened out, and practical applications in risk studies are presented.     

Distribution of moist and dry pores in a moist porous material (a probability model)

We propose a model and a method for the calculation of the concentrations of completely fluid-filled, partially moist, and dry pores in a moist porous material. The method is based on the probability approach in which the distribution of fluid in pores is accomplished by means of scattering through the pores in random fashion of quantities of fluid whose volume is dependent on the wetting angle.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 59, No. 2, pp. 255–259, August, 1990.     

Evaluation of non-crystalline cellulose as a novel excipient in solid dose products

Objective: The objective of this study was to evaluate non-crystalline cellulose (NCC) as a novel tablet excipient in solid oral dosage forms in comparison with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (Prosolv®, SMCC).

Significance: MCC, although a widely used tablet excipient, has diasdvantages in terms of its low dilution potential for potent drugs, and sensitivity to lubricant and moisture. SMCC, a modified version of MCC, has improved tablet compression properties. However, SMCC is expensive and also affects the moisture sorption and particle deformation during compression leading to increased tensile strength and tablet hardness. NCC was found to be similar to SMCC in its performance as a tablet excipient and thus can serve as a cheaper alternative to SMCC.

Methods: Scanning electron microscopy (SEM), X-ray diffrectometry (XRD), and differential scanning calorimetry (DSC) analyses were performed on NCC, MCC, and SMCC. Further, out-of-the die Heckel, Kawakita compact densification and stress-strain analyses were performed to evaluate their compaction and compressibility properties. Various compendial and non-compendial tests were performed to to determine the flow properties of materials. Dissolution studies were performed using amlodipine besylate as a marker drug.

Results: It was found that NCC has similar or even better flow properties and compactibility than MCC due to its porous and amorphous structure whereas it had similar properties as SMCC.

Conclusions: Based on the data, it can be concluded that NCC can serve as a cheaper and better alternative to MCC as excipient in solid dosage forms.     

Speciation of heavy metals in sediment by conventional, ultrasound and microwave assisted single extraction methods: a comparison with modified sequential extraction procedure

Sequential extraction procedure proposed by the European Standards, Measurements and Testing (SM&T) Program, formerly the Community Bureau of Reference (BCR), has been applied for the heavy metals (HMs) partitioning in fresh water lake sediment samples. The results obtained by conventional sequential extraction BCR method (SEB) for Cd, Cu, Cr, Ni, Pb and Zn were compared with those estimated from three alternative single extractions, conventional (CSE), ultrasonic (USE) and microwave assisted (MSE), using identical operating conditions applied in each individual BCR fraction and validated by the CRM BCR 701. Extractable HMs contents obtained by all compared methodologies were measured by atomic absorption spectrometery. With the use of compromised sonication and microwave conditions, steps 1-3 of the sequential extraction (excluding the hydrogen peroxide digestion in step 3) could be completed between 15-30 min using ultrasonic bath, while 60-120 s were required for MSE. The total extractable metal contents obtained by three single extractions ranged from 75.1% to 114.0% except Cr in first step, which was extracted (125.3%) by MSE method as compared to those obtained by SEB procedure. The precision of the proposed BCR single extraction methods (expressed as RSD%) was found in the range of (3.99-9.6%) for all metals.     

Application of fluidized hot-melt granulation (FHMG) for the preparation of granules for tableting; properties of granules and tablets prepared by FHMG

The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.     

Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique

Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 µm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage.     

A comparison of theoretical and experimental methods of calibrating the electrical potential drop technique for crack length determination

The calibration of the do pd technique for determining crack length in compact tension, corner notched and fin cracked test pieces is described. Good agreement is shown between finite element, conducting paper and specimen beach marking methods.

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Résumé On décrit le calibrage d'une technique PD (Potential Drop) en courant continu pour déterminer la longueur d'une fissure dans des éprouvettes de traction compactes comportant un entaillage sur un coin ou une nervure fissurée. On trouve un bon agrément entre les méthodes par élément fini, par papier conducteur, et par repérage des plages de propagation de fissure après rupture.

     

Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study

Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.     

Evaluation of processing methods for a calcia-yttria-alumina-silica glass-ceramic

A glass-ceramic in the calcia-yttria-alumina-silica system was prepared through the melt, sinter, sol-gel and solution routes. The development of a calcium yttrium silicate phase was found to depend significantly on the method of processing the glass. This is attributed to the strong influence of the surface/interface on reactivity. X-ray diffraction and Fourier transform infrared techniques were used for identification. The processing methods were also evaluated and compared for product quality and economy in cost.