Optimization of the process variables of roller compaction,on the basis of granules characteristics (flow,mechanical strength,and disintegration behavior): an application of SeDeM-ODT expert system

The objective of the study was application of SeDeM-ODT expert system for optimization of process variables for roller compaction and for the preparation of granules with better flow, compressibility, and disintegration behavior. In the present study, granules were prepared at pre-determined (on the basis of factorial design) process variables and characterized using SeDeM-ODT expert system. Compatibility of ribavirin with excipients (microcrystalline cellulose, tablettose-80, cross carmellose sodium, and magnesium stearate) was evaluated by binary mixture approach, using FTIR. According to the SeDeM-ODT expert system, granules were characterized for various parameters related to flow, compressibility and disintegration behavior and Index of Good Compressibility and Buccodispersibility (IGCB) was calculated. The process variables resulting in highest IGCB value were considered as optimum. Ribavirin was found compatible with all the excipients used in the study and characteristics peaks were present in FTIR spectra after subjecting to stress conditions (75% relative humidity at 45?±?5?°C) for 30?days. Both Ribavirin powder and Ribavirin containing powder blend had poor flow and compressibility while disintegration behavior was good due to higher water solubility. Screw speed of 35?rpm and roller speed at 12?rpm resulted in granules with acceptable characteristics. The IGCB value (5.63) of the granules was highest of all, indicating its better characteristics. SeDeM-ODT expert system presents a more practical picture of the granules and also predicts the mechanical strength and disintegration behavior of the tablets prepared from the granules. By proper optimization of screw and roller speed, efficiency of the process can be improved.     

温压技术中的致密化机制

根据聚合物的流动特性和粉末成形特点 ,试验研究了温压条件下金属粉末的塑性变形 ,理论分析了温压技术中的聚合物膜的成形和致密化机制。结果表明 :在压制初期 ,聚合物良好的流动性和较低的摩擦因数改善了金属粉末的充填行为。在压制末期 ,聚合物在金属表面形成一层微米或亚微米级薄膜。这层薄膜与基体结合牢固 ,将金属粉末与粉末隔离开来 ,促进粉末的塑性变形。     

温压技术及其致密化机制的研究进展

综合评述了国内外温压技术的研究进展,并对其致密化机制进行了探讨。在此基础上,对今后的研究方向提出了几点建议。     

Is the adjustment of the impeller speed a reliable attempt to influence granule size in continuous dry granulation?

As the field of continuous manufacturing of solid pharmaceutics is developing, the interest in implementing continuous granulation methods is growing. Process analytical technology tools should be integrated to ensure the monitoring of the product quality and therefore enforce control strategies.Three single materials which are often used in dry granulation and additionally two formulations, one containing ibuprofen and the other acetaminophen were processed at various process parameters. They all differed in their compaction and fracture behavior. A statistical analysis of the influence of process parameters was executed, to work out which parameters could be used for a granule size control approach in continuous dry granulation. Thereby, the specific compaction force and the impeller speed were found to be significant factors in each design of experiment. However, the impeller speed was evaluated as the only suitable parameter to control granule size, as an impact on granule density is unlikely. Nevertheless, some restrictions such as an upper impeller speed limitation to avoid excessive fines and a lower speed limitation to impede a downturn of the throughput, have to be considered. Furthermore, a decreasing median granule size was observed at higher throughputs for plastically deforming materials and formulations.     

An Analytical Model for Explosive Compaction of Powder to Cylindrical Billets through Axial Detonation

An analytical model, describing an explosive compaction process performed axially on a powder assembly of cylindrical geometry, is discussed. The powder is encapsulated in a cylindrical metal container surrounded by an explosive pad, which is detonated parallel to the major axis of the compact. The pressure generated in the powder is a function of the nature and the thickness of the explosive material as well as the powder characteristics. The model is based on the principle of shock propagation in powder aggregate and, the detonation as well as the refraction wave characteristics of the explosives. For the purpose of validation and illustration, this investigation considers the explosive compaction of aluminium powder particles for different explosive pad thicknesses. The model brings-out a closed-form solution for densification of powders. The density of the final powder compact depends on the pad thickness. Inadequate pad thickness leads to under compacted core, while higher pad thickness leads to melting at the core leading to over all low density. The optimum pad thickness of the explosive to produce the highest densification is thus determined using the model. The densification depends on the size of the powder particles also, since; the heat generated by the high pressure shock wave melts the surface of the powder particles depending on the specific heat, thermal conductivity and the latent heat of the powder material. The study essentially covers the effect of the explosive pad thickness and the particle size of the powder on densification. The analytical results are compared with a few experimental data and the comparison is found to be satisfactory.     

A novel method for estimating solid fraction of roller-compacted ribbons

A simple method has been developed to estimate solid fraction or relative density of compacts using the weight of ribbons produced during roller compaction. The method provides an alternative to the commonly used dimensional measurement, especially for formulations not amenable to forming quality ribbons. Surface texture of the compaction rolls has been taken into consideration in our mathematical treatment along with correction for ribbon relaxation. Ribbon relaxation occurring upon ribbon exiting the compaction zone is estimated using roll geometry, roll gap, and ribbon thickness. Detailed experimental runs have been carried out to confirm the validity of the proposed theory. The predicted solid fraction was found comparable to that from actual dimensional measurement by caliper. In the case of the microcrystalline cellulose/dicalcium phosphate one:one formulation, the predicted solid fraction had an error sum of squares (SSE) of 2.64E-03 when compared to the dimensional method. When relaxation was included, the SSE decreased by four folds. Similarly, for the microcrystalline cellulose/lactose monohydrate 2:1 formulation, the SSE decreased twelfth folds when relaxation was taken into consideration. These results further confirm the utility of the proposed throughput method for estimating the solid fraction of ribbons.     

A Novel Method for Estimating Solid Fraction of Roller-Compacted Ribbons

A simple method has been developed to estimate solid fraction or relative density of compacts using the weight of ribbons produced during roller compaction. The method provides an alternative to the commonly used dimensional measurement, especially for formulations not amenable to forming quality ribbons. Surface texture of the compaction rolls has been taken into consideration in our mathematical treatment along with correction for ribbon relaxation. Ribbon relaxation occurring upon ribbon exiting the compaction zone is estimated using roll geometry, roll gap, and ribbon thickness. Detailed experimental runs have been carried out to confirm the validity of the proposed theory. The predicted solid fraction was found comparable to that from actual dimensional measurement by caliper. In the case of the microcrystalline cellulose/dicalcium phosphate one:one formulation, the predicted solid fraction had an error sum of squares (SSE) of 2.64E-03 when compared to the dimensional method. When relaxation was included, the SSE decreased by four folds. Similarly, for the microcrystalline cellulose/lactose monohydrate 2:1 formulation, the SSE decreased twelfth folds when relaxation was taken into consideration. These results further confirm the utility of the proposed throughput method for estimating the solid fraction of ribbons.     

工艺因素对C/C复合材料ICVI致密化的影响

以2D针刺碳毡为预制体、丙烯为前驱气体、氮气为稀释气体,在常压条件下研究了沉积温度、滞留时间和丙烯分压等工艺因素对致密化速度的影响。结果表明,三个工艺参数协同作用,对致密化具有相似的影响：参数取值较高时初期致密化速度也较快,结果导致预制体表层气孔的过早填充,不利于进一步的沉积,反之,则致密化速度较慢,但有利于预制体内部的沉积。     

A numerical model for the cyclic deterioration of railway tracks

An elasto‐plastic material model is proposed that can be used to simulate the cyclic deterioration of railway tracks. The model describes the envelope of the irreversible, plastic material response generated during a cyclic loading process, thereby distinguishing the mechanisms of frictional sliding and volumetric compaction. The reversible response is represented by a pressure‐dependent, hypo‐elastic material law. After the numerical integration of the model is specified, the model is calibrated on laboratory experiments and employed in a finite‐element case study of the long‐term settlement behaviour of a railway track. The main features of the model are illustrated by comparing the computed response with the response obtained by in situ track measurements. Copyright © 2003 John Wiley & Sons, Ltd.     

多元耦合场CVI法快速致密化炭/炭复合材料研究

以液化石油气为碳源气体,采用多元耦合场CVI工艺方法快速制备了炭/炭复合材料.在自制冷壁CVI炉中,使用普通炭毡作为炭纤维预制体,设置特殊的导电发热层,沉积温度为650～1050℃,系统的气氛压力为0.1～30kPa,流量为0.1～0.5m3/h,沉积时间12h的条件下可将预制体一次性快速增密至1.75g/cm3.XRD分析表明:该材料经过2300℃,2h高温石墨化处理,其石墨化度(g)可达到61.3%,晶粒尺寸达到16.1nm.PLM分析表明所得材料偏光形貌表现为光滑层(SL)结构,SEM形貌照片测算可知热解炭沉积速率在6.6μm/h以上.分析了炭/炭致密化的过程和热解炭的沉积机理,说明多元耦合场加速了热解炭的沉积,缩短了致密化时间,降低了成本.     

Application of Fluidized Hot-Melt Granulation (FHMG) for the Preparation of Granules for Tableting; Properties of Granules and Tablets Prepared by FHMG

ABSTRACT

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.     

Multiphase versus Single Pot Granulation Process: Influence of Process and Granulation Parameters on Granules Properties

ABSTRACT

High-shear wet granulation is widely used for the production of pharmaceutical dosage forms. Different equipment is available for high-shear granulation and drying. This review focuses on two main processes for granules production: multiphase consisting of high-shear granulation followed by drying in a separate apparatus, and single pot granulation/drying. At present, formulas are specifically developed with regard to the production equipment, which raises many problems when different industrial manufacturing equipment is used. Indeed, final granules properties are likely to depend on equipment design, process, and formulation parameters. Therefore, a good understanding of these parameters is essential to facilitate equipment changes.

The aim of this review is to present the influence of equipment, process, and formulation parameters on granules properties, considering both the granulation and the drying steps of multiphase and single pot processes.     

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.     

Tablet formulation of an active pharmaceutical ingredient with a sticking and filming problem: direct compression and dry granulation evaluations

Objective: To develop a tablet formulation for an active pharmaceutical ingredient for which sticking and filming problems occurred during tablet punching.

Methods: Direct compression and dry granulation tableting techniques were evaluated using factorial experimental design. The effects of chrome-coated punch tips, filler types and active percent in the tablet formulation by direct compression were evaluated. Similarly, for dry granulation using the roller compaction technique, three formulation factors – roller compaction pressure, intragranular filler percent and filler type – were studied. Tablets prepared by both techniques were characterized in regard to their compressibility index, tablet hardness, disintegration time, friability index and stickiness-filming index (an arbitrary index). Ten formulations were prepared by each technique. Using multiple response optimizations and estimated response surface plots, the data were analyzed to identify optimum levels for the formulation factors.

Results: Compressibility index values for all the formulations prepared by direct compression exceeded 25%, unlike the blends prepared by dry granulation. Both tablet hardness and disintegration time for direct compression formulations were significantly lower than for dry granulation formulations. The friability index values were significantly higher for direct compression formulations than for dry granulation formulations. All the direct compression formulations, unlike the dry granulation formulations, had a high stickiness-filming index.

Conclusion: Statistical analysis helped in identifying the optimum levels of formulation factors, as well as the method for eliminating sticking and filming. Unlike the direct compression technique, dry granulation yielded tablets for which sticking and filming were completely eliminated.     

Multiphase versus single pot granulation process: influence of process and granulation parameters on granules properties

High-shear wet granulation is widely used for the production of pharmaceutical dosage forms. Different equipment is available for high-shear granulation and drying. This review focuses on two main processes for granules production: multiphase consisting of high-shear granulation followed by drying in a separate apparatus, and single pot granulation/drying. At present, formulas are specifically developed with regard to the production equipment, which raises many problems when different industrial manufacturing equipment is used. Indeed, final granules properties are likely to depend on equipment design, process, and formulation parameters. Therefore, a good understanding of these parameters is essential to facilitate equipment changes.

The aim of this review is to present the influence of equipment, process, and formulation parameters on granules properties, considering both the granulation and the drying steps of multiphase and single pot processes.     

中厚板轧机支承辊中心疏松压实过程的有限元模拟研究

基于 Gleeble 热模拟压缩实验和 Arrhenius 方程建立了 70 Cr3Mo 的本构模型,运用 Deform-3 D 软件对支承辊的多工步锻造过程进行了有限元模拟,得到了镦粗和拔长过程中压下量和中心疏松密度的关系,对比研究了平板镦粗和锥板镦粗对中心压实的影响。     

The performance of HPMC matrix tablets using various agglomeration manufacturing processes

Context: The flow and compaction properties of a compaction mixture or powder and the drug-release profile of final tablets are important critical quality attributes (CQAs) that have an impact on the overall performance of hydrophilic matrix tablets. The selection of granulation method can importantly affect these CQAs.

Objective: This study investigates various agglomeration methods of sustained-release formulation using HPMC K4M as a release polymer with various wet- and dry-granulation techniques.

Materials and methods: Flow properties were determined using flow time, angle of response, and the Carr index. Compaction properties were evaluated using “out of die” Heckel model. Release of carvedilol was tested as 12-h drug-dissolution profile.

Results and conclusion: Compression mixtures made using the wet-granulation method exhibit better flow and compression properties than compression mixtures made using the dry-granulation method. The direct compression method proved to be the least appropriate manufacturing method because the compression mixture has very poor flow and the lowest compressibility/compactibility index. The choice of granulation technique significantly influences the swelling behavior and drug-dissolution profile of the final matrix tablets, also resulting in dissimilar release profiles. The choice of granulation method has the greatest influence on the drug-release profile. The direct compression method provides tablets with the fastest drug-release profile, followed by the dry-granulation and wet-granulation methods. The particle size of granules and porosity of tablets play an important role, contributing to differences in drug-release profiles.     

粉末冶金温压工艺的技术特点及其新发展

本文概述了温压工艺的特点及其最新的发展,如流动温压、热模压制等,重点讨论了热模压制工艺的技术特点与应用,并指出以AncorMax D为代表的热模压制工艺由于工序比常规温压工艺更简单,压制温度更低,因此在将来很有可能取代常规温压工艺,成为高密度粉末冶金零件的一种非常有应用前景的方法.