Prolonged release Matrix Pellets Prepared by Melt Pelletization I. Process Variables

Abstract

A melt pelletization process was investigated in an 8 litre laboratory scale high shear mixer using a formulation with paracetamol, glyceryl monostearate 40–50, and microcrystalline wax. The effects of jacket temperature, product temperature during massing, product load, massing time and impeller speed were investigated by means of factorially designed experiments. The maximum yield of pellets in the range of 500–1400μm was found to approx. 90%. For process conditions preventing deposition of moist mass, the process was found to be reproducible. Impeller speed and massing time were found to be important process variables. Remarkably low in vitro drug release rates were observed in USP-dissolution tests.     

New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach

The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X₁), impeller speed (X₂), wet massing time (X₃), and water addition rate (X₄) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p?相似文献   

Melt Granulation in A Laboratory Scale High Shear Mixer

The applicability of a 10 litre high shear mixer for melt granulation of dicalcium phosphate and lactose is examined. Polyethylene glycol (PEG) 3000 and 6000 were used as melting binders in concentrations of 15-20% w/w. The effects of binder concentration, massing time, impeller speed, and particle size of the PEG 6000 on granule size, granule size distribution and intragranular porosity are investigated.

It is shown that pellets of a narrow size distribution can be produced by the use of a high impeller speed. Granule size and size distribution are markedly influenced by binder concentration and massing time. The particle size of the PEG has only a minor effect on the granule growth. Granule growth mechanisms by melt granulation are discussed on the basis of the liquid saturations and the amounts of binder liquid and are compared with previous results on wet granulation.     

Melt Granulation in A Laboratory Scale High Shear Mixer

Abstract

The applicability of a 10 litre high shear mixer for melt granulation of dicalcium phosphate and lactose is examined. Polyethylene glycol (PEG) 3000 and 6000 were used as melting binders in concentrations of 15-20% w/w. The effects of binder concentration, massing time, impeller speed, and particle size of the PEG 6000 on granule size, granule size distribution and intragranular porosity are investigated.

It is shown that pellets of a narrow size distribution can be produced by the use of a high impeller speed. Granule size and size distribution are markedly influenced by binder concentration and massing time. The particle size of the PEG has only a minor effect on the granule growth. Granule growth mechanisms by melt granulation are discussed on the basis of the liquid saturations and the amounts of binder liquid and are compared with previous results on wet granulation.     

High shear wet granulation: Improved understanding of the effects of process variables on granule and tablet properties of a high-dose,high-hydrophobicity API based on quality by design and multivariate analysis approaches

High shear wet granulation (HSWG), as a widely used granulation technology, has been studied extensively. However, for the HSWG of formulations containing hydrophobic components, the influence of process variables on the properties of granules and tablets has not been reported. In the present study, based on a combination of quality by design and multivariate analysis (MVA) approaches, quercetin with high-dose and high-hydrophobicity was used to study the relationship between process variables, granule properties, and tablet properties in HSWG systematically. Control and response variables were determined using risk assessment. The optimal fitting empirical models established by Box-Behnken design showed that the liquid to solid ratio and impeller speed were the most important factors, which affected all product properties except Carr’s index and yield pressure. Instead, the influence of wet massing time was relatively small (only the effects on yield, granule size, granule hardness, and compression ratio were significant). Then, the process design space was obtained by limiting the related critical quality attributes, which was verified effectively. Scanning electron microscope images showed that smooth granules were produced using higher process parameters, whereas rough and porous granules resulted at lower process parameters. Furthermore, the MVA results demonstrated that increasing the granule hardness led to an increase in the compression ratio and a decrease in tensile strength of the tablets. Tablet fragility and disintegration time were mainly affected by granule density and bulk density, respectively, and both were negatively correlated. The established research paradigm is not only conducive to the successful development of quercetin products, but also provides valuable guidance for improving HSWG–based product development with such formulation characteristics.     

Effective utilization of waste ash from MSW and coal co-combustion power plant: Zeolite synthesis

The solid by-product from power plant fueled with municipal solid waste and coal was used as a raw material to synthesize zeolite by fusion-hydrothermal process in order to effectively use this type of waste material. The effects of treatment conditions, including NaOH/ash ratio, operating temperature and hydrothermal reaction time, were investigated, and the product was applied to simulated wastewater treatment. The optimal conditions for zeolite X synthesis were: NaOH/ash ratio=1.2:1, fusion temperature=550 degrees C, crystallization time=6-10 h and crystallization temperature=90 degrees C. In the synthesis process, it was found that zeolite X tended to transform into zeolite HS when NaOH/ash ratio was 1.8 or higher, crystallization time was 14-18 h, operating temperature was 130 degrees C or higher. The CEC value, BET surface area and pore volume for the synthesized product at optimal conditions were 250 cmol kg(-1), 249 m(2) g(-1) and 0.46 cm(3) g(-1) respectively, higher than coal fly ash based zeolite. Furthermore, when applied to Zn(2+) contaminated wastewater treatment, the synthesized product presented larger adsorption capacity and bond energy than coal fly ash based zeolite, and the adsorption isotherm data could be well described by Langmuir and Freundlich isotherm models. These results demonstrated that the special type of co-combustion ash from power plant is suitable for synthesizing high quality zeolite, and the products are suitable for heavy metal removal from wastewater.     

The Granulation of Lactose and Starch in a Recording High-Speed Mixer,Diosna P25

Abstract

Lactose 100 mesh was granulated faster than the 350 mesh quality.

Corn starch required large volumes of granulating solution. When agglomerating pure corn starch, its loss on drying influenced the process.

Suitable limits for the end-point determination when granulating a mixture of 2/3 of lactose 100 mesh and 1/3 of corn starch, with povidone as binder, were determined for the liquid addition under controlled conditions.

In a 1/2 ? 2₆ factorial experiment, the influence of the process variables on the response variables was studied. The former are the main impeller and chopper speed; the method of fluid addition; the way of adding the binder; the volume of granulating liquid added, and the wet massing time. The response variables concerned are the fraction <0.150 or >2.00 mm; the granule median diameter; the change in the rotation rate of the impeller shaft; and heat production in the mass. The impeller and chopper speed, the way of adding the binder, and the volume of granulating solution that was added, influenced all the response variables significantly. However, the dominating variables were the volume of solution and the impeller rate. Besides, the granule median diameter was influenced by the method of fluid addition. Also, the heat production during granulation was influenced by the method of fluid addition as well as by the wet massing time.     

Etude des facteurs d'intensification de l'échange de chaleur dans le refroidissement des fruits et légumesInvestigating the factors for intensifying fruit and vegetable cooling

Increasing the rate of fruit and vegetable cooling is of economic significance for the following reasons: biochemical and microbiological processes are quickly suppressed; surface mass-exchange with ambient air is slowed down; power consumption is reduced, and the freezing output of cooling equipment and installations is increased.It was assumed that the fruits and vegetables in crates were arranged regularly and covered with thin paper of a negligible small thermal resistance in order to eliminate the infiltration of cold air within the layers. Crates were arranged on a pallet so that they touched horizontally. Thus, the packages form plates above and below the cooling air flow. Heat-exchange with a one-dimensional temperature field is established.It was found that intensification of cooling can be achieved by increasing the speed of cooling air as well as by stopping the process at a higher final temperature. Increasing the speed up to 5 m s^?1 shortens the time of the process by a factor of two compared with the low speeds (0.3–0.5 m s^?1) which are normally used. The product can be cooled until the temperature in the layer centre reaches 5°C, and the surface temperature about 2°C, which is low enough. Afterwards the cooled product is transferred to a freezing chamber or to a van-freezer. This factor results in a further halving of the cooling time. The combined effect of the two factors shortens the duration of the process by about 75% and increases the output of the cooling equipment from 3.5 to 4 times.     

Preparation and characterization of zinc sulfide nanoparticles under high-gravity environment

Nanosized ZnS particles were prepared under high-gravity environment generated by the rotating packed bed reactor (RPBR) using zinc nitrate solution and hydrogen sulfide gas as raw materials. The effects of experimental conditions such as reactant concentration, reaction temperature, rotating speed of the RPBR and aging time, on the preparation of nanosized ZnS particles were investigated. A set of suitable operating parameters (the aging time of 48 h, concentration of zinc nitrate of 0.1 mol/l, reaction temperature of 45 °C and rotating speed of the RPBR of 1500-1800 rotation/min) for the preparation of nanosized ZnS were recommended. Under these optimum conditions, well-dispersed ZnS nanoparticles was obtained. The crystal structure, optical properties, size and morphology of the product were also characterized by XRD, UV-Vis spectrophotometer, and TEM, respectively. Results indicate that the prepared ZnS has a good absorption for light in the wavelength range of 200-330 nm. XRD analysis also shows the prepared ZnS is in a sphalerite crystal phase. The process has great potential of commercialization.     

Batch sorption dynamics and equilibrium for the removal of cadmium ions from aqueous phase using wheat bran

Studies on a batch sorption process using wheat bran as a low cost sorbent was investigated to remove cadmium ions from aqueous solution. The influence of operational conditions such as contact time, cadmium initial concentration, sorbent mass, temperature, solution initial pH, agitation speed and ionic strength on the sorption kinetics of cadmium was studied. Pseudo-second-order model was evaluated using the six linear forms as well as the non-linear curve fitting analysis method. Modeling of kinetic results shows that sorption process is best described by the pseudo-second-order model using the non-linear method. The sorption of cadmium was found to be dependent on initial concentration, sorbent mass, solution pH, agitation speed, temperature, ionic strength and contact time. The value of activation energy (12.38 kJ mol(-1)) indicates that sorption has a low potential barrier corresponding to a physical process. Sorption equilibrium isotherms at different temperatures was determined and correlated with common isotherm equations such as Langmuir and Freundlich models. It was found that the Langmuir model appears to well fit the isotherm data but a worse correlation was obtained by the Freundlich model. The five Langmuir linear equations as well as the non-linear curve fitting analysis method were discussed. Results show that the non-linear method may be a better way to obtain the Langmuir parameters. Thermodynamic parameters such as DeltaH degrees, DeltaS degrees and DeltaG degrees were calculated. These parameters indicate that the sorption of cadmium by wheat bran is a spontaneous process and physical in nature involving weak forces of attraction and is also endothermic.     

稀土异戊橡胶螺杆挤压脱水膨胀干燥一步法

采用螺杆挤压脱水膨胀干燥一步法干燥稀土异戊橡胶,考察了模头温度、机筒温度、模头压力和螺杆转速对产品质量和生产能力的影响,优化了稀土异戊橡胶干燥一步法工艺参数.在优化工艺条件下获得了较好的干燥效果,门尼黏度和挥发份满足产品的应用要求.     

Synthesis of nanocrystalline SiC at ambient temperature through high energy reaction milling

This study investigated the in-situ synthesis of nanosized crystalline SiC powders at room temperature through high energy ball milling of elemental silicon and carbon mixtures. Milling conditions including the mill design, the milling speed, the milling time and the ball-to-powder weight ratio (i.e. the charge ratio) necessary for the in-situ synthesis were studied. It was found that uniform formation of nanosized crystalline SiC powders within the powder charge could be achieved with a correctly designed attritor and the contamination could be minimized with proper selections of milling conditions. The crystalline β-SiC powders synthesized were themselves in nanosize scale, quite different from many previous studies which have shown that it is the internal grain structure of milled powders that is the “nanocrystalline” component of the powders (typically 5–20 nm), while the powders are themselves typically 0.1 μm to > 1 μm in size. Furthermore, it was found that the product structures generated by high energy reaction milling depended strongly on the milling speed, the charge ratio and the milling time.     

A Factorial Approach to High Dose Product Development by an Extrusion/Spheronization Process

Extrusion/spheronization technology has been used for preparing high drug-loaded pellets. Typical formulations include 40-60% microcrystalline cellulose (MCC) to impart the plastic characteristics required for this process. Studies have suggested that pellets containing greater than 80% drug are difficult to process and require special grades of MCC. Most of these studies focused on either the process or formulation aspects of the product and failed to explore the interactions of process and product. Statistical experimental designs are well suited for exploring both process and product variables and their interactions with each other. This study addresses pelletization of a high dose drug with low density. A Nica® radial (basket-type) extruder was used in extrudate preparation, followed by spheronization on a serrated plate spheronizer. A Plackett-Burman screening design was employed to investigate product and process parameters affecting final pellet drug content, density and roundness. MCC type and concentration, water concentration, spheronizer speed and residence time and extruder screen size were found to be statistically significant in imparting desirable attributes to the final product. Wet mixing time, extruder feed rate and extrusion rate did not significantly affect pellet properties     

Optimization of a Granulation Procedure for a Hydrophilic Matrix Tablet Using Experimental Design

An experimental design was used in order to optimize a granulation procedure in a high-shear mixer for a hydrophilic matrix tablet formulation. The parameters tested were the amount of water in the hydroalcoholic granulation liquid, the amount of granulation liquid, and the massing time. The amount of granulation liquid was the most important parameter, followed by the amount of water in the granulation liquid. The influence of the massing time was negligible. A granule with a friability below 20% was obtained.     

放电等离子快速烧结纳米3Y-TZP材

本文采用放电等离子烧结技术（ＳＰＳ）快速烧结结纳米３Ｙ－ＴＺＰ材料,利用ＳＰＳ技术快速烧结,可制备出完整、致密的３Ｙ－ＴＺＰ材料,在烧结温度为１３００℃,保温３ｍｉｎ条件下,相对密度达９８．２％,晶粒仅１００￣１３０ｎｍ,研究发现,材料的密度随烧结温度的变化趋势与一般快速烧结有明显区别;材料的晶粒随烧结温度的提高而长大,但长大幅度小于其他一些烧结方法所得的３Ｙ－ＴＺＰ材料,本研究对这些现象进行了理     

Etude des facteurs d'intensification de l'échange de chaleur dans le refroidissement des fruits et légumes

Increasing the rate of fruit and vegetable cooling is of economic significance for the following reasons: biochemical and microbiological processes are quickly suppressed; surface mass-exchange with ambient air is slowed down; power consumption is reduced, and the freezing output of cooling equipment and installations is increased.It was assumed that the fruits and vegetables in crates were arranged regularly and covered with thin paper of a negligible small thermal resistance in order to eliminate the infiltration of cold air within the layers. Crates were arranged on a pallet so that they touched horizontally. Thus, the packages form plates above and below the cooling air flow. Heat-exchange with a one-dimensional temperature field is established.It was found that intensification of cooling can be achieved by increasing the speed of cooling air as well as by stopping the process at a higher final temperature. Increasing the speed up to 5 m s⁻¹ shortens the time of the process by a factor of two compared with the low speeds (0.3–0.5 m s⁻¹) which are normally used. The product can be cooled until the temperature in the layer centre reaches 5°C, and the surface temperature about 2°C, which is low enough. Afterwards the cooled product is transferred to a freezing chamber or to a van-freezer. This factor results in a further halving of the cooling time. The combined effect of the two factors shortens the duration of the process by about 75% and increases the output of the cooling equipment from 3.5 to 4 times.     

水性胃溶型丙烯酸树脂的制备

利用乳液聚合的方法制备水性胃溶型药物包衣用丙烯酸树脂,此法制备的水性药物包衣材料性能稳定,无污染,成本低,包衣效率高.分别考察了相比、乳化剂及其用量、引发剂及其用量、搅拌速度、加料方式、反应温度等对实验结果的影响.     

室外环境参数对空气源热泵翅片管蒸发器动态结霜特性的影响

对一台空气源热泵空调器在不同环境条件下室外换热器的动态结霜性能进行了实验研究，分析了进风温、湿度对热泵空调器结霜量及霜层厚度的影响。实验中考虑了结霜引起的热泵系统蒸发温度及风机流量的变化，采用显微照相法测量翅片表面霜层厚度，结霜量则通过测量蒸发器进出口含湿量的方法来获得。实验结果表明，室外换热器结霜量随时间线性增长，而翅片表面霜层厚度则分为初始段、匀速增长段和快速增长段三个阶段；在结霜循环的最后20％～30％的快速增长段内霜层生长速率大大加快，可达匀速生长段霜层生长速率的2．4，3．3倍。对于不同的工况，蒸发器均在进风温度0～3℃附近时结霜最为严重，且相对湿度对霜层厚度的影响要大于对结霜量的影响。