The Quantitative Evaluation of a Granulation Milling Process III. Prediction of Output Particle Size

Abstract

Regression analysis was performed using comminution data from the previously presented Comil®G/aspirin granulation characterization study. Polynomial models were constructed using mill speed, output screen size and impeller shape as independent variables. The models were used to predict the mean particle size (µ_d) and geometric standard deviation (σ_d) of particle size distributions resulting from the comminution of aspirin using the Comil®G. The predictions were found to compare well with observed values.     

The Quantitative Evaluation of a Granulation Milling Process I. Algebraic Method for Particle Size Analysis

A method is presented which may be used to mathematically express particle size distributions of pharmaceutical granulations.

The method utilizes expresses of particle size and probability evaluated using a weighted linear regression technique. This method is suggested whenever particle size determinations are used in conjunction with statistical analysis, optimization techniques or any time a purely quantitative approach is needed.     

The Quantitative Evaluation of a Granulation Milling Process II. Effect of Ouput Screen Size, Mill Speed and Impeller Shape

The processing variables associated with the comminution of pharmaceutical granulations were investigated. The three variables chosen were mill speed, output screen size and impeller shape. Experiments were performed on an aspirin granulation using proper techniques of experimental design. Analysis showed that the three mill variables cannot be considered independently but rather at the level of combinations. A complete characterization of the mill output according to particle size distribution is then possible based upon these combinations of mill variables.     

The effect of Mill Variables on a Granulation Milling Process

An instrumented mill was used to evaluate the milling of a pharmaceutical granulation. The effects of changing mill speed, screen hole size, impeller type, and impeller-screen clearance on milling time and work, as well as particle size reduction were investigated. Screen hole size had the largest effect on milling time and work as well as particle size reduction, while impeller type had the largest effect on overall milling performance. A new impeller design was tested and found to enhance milling efficiency by improving both particle size reduction and mill output rate.     

The effect of Mill Variables on a Granulation Milling Process

Abstract

An instrumented mill was used to evaluate the milling of a pharmaceutical granulation. The effects of changing mill speed, screen hole size, impeller type, and impeller-screen clearance on milling time and work, as well as particle size reduction were investigated. Screen hole size had the largest effect on milling time and work as well as particle size reduction, while impeller type had the largest effect on overall milling performance. A new impeller design was tested and found to enhance milling efficiency by improving both particle size reduction and mill output rate.     

球磨工艺对钡铁氧体浆料粒径和磁性能的影响

研究钡铁氧体永磁材料制备过程中,球磨时间和分级球磨等球磨工艺对浆料粒度的影响,以及浆料粒度对钡铁氧体磁性能的影响。结果表明:在高能球磨过程中,浆料粒径随球磨时间增加呈减小趋势,当球磨时间超过其极限值后基本保持不变。采用分级球磨后浆料粒径明显减小,且颗粒粒径分布均匀,但只有采用合适的球磨工艺才能达到最好的分散效果。钡铁氧体永磁材料的取向度、剩余磁化强度随颗粒粒径的减小呈增大趋势。     

An Evaluation of Process Variables in wet Granulation

Abstract

In wet granulation, determining the process variables which play an essential role in granule quality is crucial for optimizing the manufacturing process. An L16(2⁵) fractional factorial experimental design using the table of orthogonal arrays was employed in order to estimate the relative intensity of the influences of five process variables on granule quality in wet granulation using a high-speed mixer granulator. Total volume and formulation of binder solution, blade rotation speed, granulation time, and amount of powder supplied into the granulator were selected as decisive process variables in the formation of granules. Granule yield, geometrical mean granule size and uniformity of granule size were evaluated as representative properties of granule quality. Experimental results were analyzed according to the analysis of variance (ANOVA).

The results of significance test and contribution ratio in ANOVA indicated that, within the experimental region, only binder solution had a critical effect on the three physical properties of the obtained granules. The effects of other variables were found to be minimal. Further, the contribution of sampling error to total variance was quite small.     

Particle Size Determination of a Three-Component Suspension Using a Laser-Scattering Particle Size Distribution Analyzer

In this study, a rapid and accurate particle size determination method using a light-scattering particle size analyzer was developed to measure the particle size and size distribution of a suspension containing three solid components: clotrimazole, triamcinolone, and sarafloxacin, which have different refractive indices. To ensure that data represent the size distribution of the primary particles of the suspension, the optimal sonication prior to and during measurement was detemined. It was found that the results obtained using the average relative refractive index (RRI) of the three components agreed with the results obtained using three individual RRIs. In addition, the results from two analysts demonstrated good reproducibility of this method. The size distribution data of the suspension were also compared to those of the bulk drugs. The results showed that the median particle size of this three-component suspension is relatively close to that of clotrimazole, which accounts for 80% of solid particles in the suspension. Furthermore, the results obtained using the light-scattering technique were comparable to those obtained using a polarized light microscope equipped with an image analyzer, indicating acceptable accuracy of this technique.     

激光粒度仪颗粒联测的结果与评价

为了解不同激光粒度仪的硬件、软件等方面差异对粒度测量结果的影响,用4种颗粒形状不同的粉末在不同公司生产的激光粒度仪上进行测试。结果表明:激光粒度仪测试结果重复性很好;对于球形粉末和形状较规则的粉末,大部分激光粒度仪测得的中位径值之间可以比较;而粒径范围较宽和不规则形状粉末,个别仪器测量的中位径值有差异。     

激光粒度分析仪粒径示值误差的测量结果不确定度评定

本文详细介绍激光粒度分析仪颗粒平均粒径示值误差的测量不确定度来源及合成、扩展不确定度的评定方法。     

化学法镀膜过程中溶胶颗粒特性的研究

溶胶-凝胶法制备的光学薄膜具有优良的物理化学特性和广阔的应用前景。通过对整个化学法镀膜过程的分析，发现溶胶中胶体颗粒粒径的大小决定胶体颗粒之间的搭接，从而直接决定着所镀薄膜表面形貌和平整度。采用激光粒度仪对氧化锆溶胶的颗粒特性进行了为期28天的观测，发现氧化锆胶体平均粒径保持在10nm左右，有逐渐增大的趋势，溶胶保存时间在20天以内较为适合镀膜。用原子力显微镜观测薄膜的表面相貌，所镀薄膜均匀，平整度小于5nm。可见采用激光粒度仪对溶胶颗粒粒径变化进行监控，能有效提高所镀薄膜的成膜特性，对溶胶镀膜的大规模生产和工艺成熟有一定的指导意义。     

化学法镀膜过程中溶胶颗粒特性的研究

溶胶-凝胶法制备的光学薄膜具有优良的物理化学特性和广阔的应用前景.通过对整个化学法镀膜过程的分析,发现溶胶中胶体颗粒粒径的大小决定胶体颗粒之间的搭接,从而直接决定着所镀薄膜表面形貌和平整度.采用激光粒度仪对氧化锆溶胶的颗粒特性进行了为期28天的观测,发现氧化锆胶体平均粒径保持在10 nm左右,有逐渐增大的趋势,溶胶保存时间在20天以内较为适合镀膜.用原子力显微镜观测薄膜的表面相貌,所镀薄膜均匀,平整度小于5nm.可见采用激光粒度仪对溶胶颗粒粒径变化进行监控,能有效提高所镀薄膜的成膜特性,对溶胶镀膜的大规模生产和工艺成熟有一定的指导意义.     

颗粒计数仪在氧化铝生产种分过程中的应用

通过对现代粒度分析方法的分类和比较,根据氧化铝生产种分过程中粒度分析的特点,认为电阻颗粒计数法是比较适合应用于氧化铝生产种分过程的粒度分析方法.对Elzone5382颗粒计数仪的原理及其在氧化铝生产中的应用进行了介绍,并对应用该粒度仪进行粒度测试过程中的影响因素进行了初步探讨.     

显微图像法测量颗粒粒径的不确定度评定

采用显微图像法测量某球形玻璃微珠颗粒的平均粒径,从测试重复性、显微图像内标法粒径测量等方面对影响颗粒粒径测量结果的不确定度进行分析和阐述,并对各不确定度分量进行计算和合成,最终给出颗粒粒径测量的不确定度报告。结果表明,当采用扫描电镜内标法在放大倍率为200时,球形玻璃微珠颗粒的数量平均粒径的扩展不确定度为5.3%,有效自由度为96。     

The Effect of the Wet Granulation Process on Drug Dissolution

Abstract

Wet granulation can be an important processing step for pharmaceutical solid dosage forms. In this investigation emphasis was directed towards the influence of a “simple” wet granulation process on drug release from granules and their resulting tablets. Direct compression blends of the same materials were used as controls. Binary mixtures containing a 5% level of either theophylline, hydrochlorothiazide or chlorpheniramine maleate in microcrystalline cellulose or lactose were granulated with water. Experimentally, the powders were dry blended in a planetary mixer, wet granulated, and subsequently wet milled and dried. No dry milling step was included. Granule characterization consisted of particle size, density, porosity, compression and dissolution testing. Dissolution results varied with the drug, as expected, and dissolution at 10 minutes ranged from 35 to 95 % release. In general, however, the results indicate that dissolution from granules and the corresponding direct compression blend are similar. Although differences in compressibility were observed in the systems studied, granulation was not found to be detrimental to drug release.     

Evaluation of Particle Size Distribution and Specific Surface Area of Magnesium Stearate

The geometric mean diameter and several other particle size distribution parameters of nine lots of magnesium stearate from Mallinckrodt Inc. and one lot from Witco Corporation were determined using a light scattering particle size analyzer. Similarly, the specific surface area of these lots was also determined using both single and multi-point B.E.T. methods. A regression analysis of the data indicated that there was a good correlation between the specific surface area and the geometric mean diameter of the various samples. Also, the volume mean diameter, the sauter mean diameter, the 10th, 50th and 90th percentile points, and the span values were consistent with the geometric mean diameter data. The results of this study indicate that the use of a light scattering particle size analyzer provides a quick, simple and reliable technique for evaluating the batch-to-batch variability in magnesium stearate.     

Simultaneaus Optimization of Several Response Variables in a Granulation Process

Wet granulation of lactose and corn starch in a 10 litre high shear mixer was examined. The optimal combination of three indipendendent variables (moisture level, impeller speed and granulation time) on four properties of the granules was investigated by simultaneaus optimization method.

The optimun zone determined in 10 litre high shear mixer was analyzed for scaling-up study. The same product was manufacted at 50 L scale and optimum theoretical results were obtained for the four response variables and are comparable with the experimental results.     

气流磨生产过程中喂料速率对粒度的影响

为在流化床式气流磨进行生产时合理选择喂料速率,以获得较好的产品,通过小型气流磨加工滑石粉实验,分析不同分级轮转速下磨腔料位、产品中位径与喂料速率之间的关系,以及喂料速率对产品粒度的影响。结果表明,提高分级轮转速,可以很明显地减小产品中位径;当物料粉碎过程进入稳定状态以后,分级轮的每一个转速都对应一个喂料速率的临界值,在一定的分级轮转速下,把喂料速率调整到最佳值,可以获得粒度更细、分布更窄的产品;喂料速度控制不好将引起分级轮电机过载,产品粒度不稳定,设备产能降低。     

Integrated Population Balance Model Development and Validation of a Granulation Process

This study is concerned with the development of an integrated three-dimensional population balance model (PBM) that describes the combined effect of key granulation mechanisms that occur during the course of a granulation process. Results demonstrate the importance of simulating the different mechanisms within a population balance model framework to elucidate realistic granulation dynamics. The incorporation of liquid addition in the model also aids in demarcating the dynamics in different regimes such as premixing, granulation (during liquid addition) and wet massing (after liquid addition). For the first time, the effect of primary particle size distributions and mode of binder addition on key granule properties was studied using an integrated PBM. Experimental data confirms the validity of the overall model as compared to traditional models in the literature that do not integrate the different granulation mechanisms.