Power of experimental design studies for the validation of pharmaceutical processes: case study of a multilayer tablet manufacturing process

Experimental design studies (EDS) are already widely used in the pharmaceutical industry for drug formulation or process optimization. Rare are the situations in which this methodology is applied for validation purposes. The power of this statistical tool, key element of a global validation strategy, is demonstrated for a multilayer tablet manufacturing process. Applied to the Geomatrix® system generally composed of one compression and three granulation processes, time and strictness gains are non-negligible. Experimental design studies are not used in this work for modeling. Introduced at each important step of the process development, they allow for the evaluation of process ruggedness at pilot scale and specifications for full production. A demonstration of the complete control of key process parameters is given, identified throughout preliminary studies.     

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.     

Using an Experimental Design to Identify and Quantify the Effects of Environment Related Test Parameters on the In Vitro Mucoadhesivity Testing of a Propanolol Buccal Tablet

ABSTRACT

This study sought to identify and quantify the effects of environmental test parameters on the mucoadhesivity of a propranolol tablet. Their effects on Maximum Detachment Force (MDF) measurements were evaluated using a Box-Behnken design matrix. Prehydration time (PT) had a statistically significant negative main effect while contact force (CF) had no significant effect on in vitro MDF measurements. While contact time (CT) had no significant main or quadratic effects, it had a positive interaction effect with PT. The mathematical model was statistically validated and a PT of 3.5 min and a CT of 5 min was proposed for mucoadhesion testing by the tensile method during formulation optimization.     

Multivariate Methods in the Development of a New Tablet Formulation: Optimization and Validation

In a previous study of the development of a tablet formulation approximately 100 excipients were characterized in screening experiments using multivariate design. Acceptable values for important responses were obtained with some of the formulations. The relationships between the properties of the excipients and the responses were evaluated using PLS. In this study additional experiments were performed in order to validate models obtained from the screening study and to find a formulation of suitable composition with desired tablet properties. A formulation with the desired disintegration time was found with the additional experiments and the agreement between observed and predicted values was fair for the tablets that did disintegrate. A limitation of this study was that tablets from four experiments did not disintegrate within the set time limit. The lack of agreement between observed and predicted values of these four experiments was probably due to the nature of one of the factors in the design. Considering the reduced experimental design the results are still encouraging.     

论探寻平板电脑设计机会的方法

从目前市场上平板电脑存在的定位模糊问题出发,指出在设计之初对特定人群开展针对其生活形态及行为等分析研究的必要性,并基于群体文化学理论,探讨其在模糊前期对寻找产品机会缺口的意义,提出了运用群体文化学原理在平板电脑开发设计前期的具体应用程序与方法,为相关新产品机会缺口的寻找及产品定位,提供了可操作的方法和步骤。     

A Model for the Design Process Gene Based on the Extensible Basic-element and the Mutation of the Design Process Gene

In this paper a method is developed to model the design process gene based on the extensible basic-element with the purpose of design process optimization and reuse. First, the principle of genetic engineering based design process optimization and reuse is put forward and analyzed. Second, the extensible basic-element model of the design process gene is established based on the models of the design process base and the base pair through analyzing the concept and structure of the design process gene and the extensible basic-element as well as its extensibility. Third, the features of divergence and scalability of the extensible basic-element model of the design process gene are discussed for carrying out the extension translation to the design process gene by way of inserting, deleting and updating design process bases. Finally, an example of building extensible basic-element models for the design process base, base pair and design process gene in mechanical product design and the mutation process of the design process gene in airplane design is presented which demonstrates the application of the method proposed in this paper.     

某产品定位套加工制造工艺改进

对某产品定位套加工工艺方式进行了分析和论证,并制定了相应的改进措施和加工工艺流程,通过实践证明,工艺改进后产品质量稳定,减少了废品损失,降低了生产成本,具有可观的经济效益。     

无石棉胶乳抄取纸的均匀配方设计及性能研究——密度

无石棉胶乳抄取纸制备过程中,有效可行的配方设计方案是密封材料性能的重要保证.设计和拟合了U12(124×3×42)均匀设计表,确定7个自变量以及在自变量范围内的12个水平的配方试验方案,对制备得到的抄取纸进行了密度性能测试,并用多元线性回归方法考察了密度与配方组分的关系.结果表明,有机纤维,特别是芳纶浆粕对拉伸强度的影响很大,芳纶浆粕含量的增加有助于密度的增大;填料对密度的作用较小;在其他组分固定时,过分增加白炭黑含量,反而使密度有所降低.同时利用得到的回归方程对试样的配方进行了性能预测,且预测值与实测值比较接近.     

内接头锻件成形工艺分析与模具设计

提出了采用预成形和正反挤成形生产内接头新工艺,通过有限元模拟和分析确定了合理的预制坯形状和尺寸,设计了内接头预成形和正反挤成形模具。     

统计过程控制在微电脑控制器生产中的应用:案例研究

以某电子集团生产的某类型控制器的实际生产为例,采用因果分析法对其生产过程中造成质量缺陷的原因从5M1E(人、机、料、法、测、环)方面进行综合分析.通过对其测量系统进行监控,在其稳定可靠的情况下采集数据.运用SPC技术对波峰焊工序进行控制图监控,对失控原因进行分析并在线调整.有效地保证了控制器的质量,为其质量改善指明了方向.     

Quality of Information Flow in the Backend of a Product Development Process: a Case Study

The increasing need for products that are able to reliably deliver complex functionality with a high degree of innovation presents a major challenge to the modern day product creation processes. In order to be able to use information on the field behaviour of previous products in the design of new products, increasingly detailed information needs to be retrieved from the market in an increasingly shorter time. The purpose of this study is to analyse, in a typical case in the consumer electronics industry, whether the underlying business process is able to generate this information with adequate quality sufficiently quickly. Information models of the company's service centre and call centre were developed using the concepts of maturity index on reliability. The results showed that the structure of the information handling process resulted in a massive data loss (up to 60% of the data gathered by the service centres) and also in serious data quality degradation. Would this information have not been lost, it could have been used by development teams for preventive and corrective actions. Copyright © 2004 John Wiley & Sons, Ltd.     

Improving the Quality of Information Flows in the Backend of a Product Development Process: a Case Study

Considerable research has gone into designing effective product development processes. This, coupled with the increasing need for products that are able to deliver reliable, complex functionality with a high degree of innovation, presents a major challenge to modern day industries in the business of developing products. In order to incorporate relevant field experience in the design and manufacturing of new products, increasingly detailed information needs to be retrieved from the market in a very short amount of time. In one particular consumer electronics industry, business process models describing the information flow in the backend of the product development process indicated massive data loss and also serious data quality degradation. This paper attempts to show how such losses can be mitigated and also proposes a business model that can adequately capture information of a higher quality and in a more structured manner. The end result will be a product development process that provides better feedback on current product performance and is more responsive to future market needs. Copyright © 2005 John Wiley & Sons, Ltd.     

IE理论在营业厅固网业务流程优化中的应用

针对营业厅固网业务服务流程繁琐、服务不及时、客户长时间排队等待的现状,基于工业工程(IE)理论,重新定义IE理论图表技术符号,应用“5W1H”提问技术分析现状,确定需要优化的项目;应用“ECRS”4大原则优化固网业务流程。以某市营业厅固网业务流程为例,优化后客户平均移动距离由69 m缩短至34 m、高峰期平均停留时间由58 min缩短至29 min,说明使用该方法优化固网业务流程效果明显。这对于提高客户满意度、提升服务质量和效率以及企业竞争实力具有指导作用。     

An Object-Oriented Modeling Approach in Materials Processing: Case Study of the Acheson and Carburizing Processes

Numerical results can be conveyed effectively to any one using an object-oriented framework. Therefore, it becomes essential to couple the object-oriented approach with numerical analysis. A simple object-oriented methodology for creating a graphical user interface (GUI) as a framework is presented. This work tries to fill a gap between scientific computer code written in a noninteractive way and interactive programming in materials processing. The GUI interface framework has been created in such a way that at any point of time one need not create a new GUI framework. The user only needs to create the process object and attach it to the framework. Two examples have been presented involving interactive finite volume-based gas carburizing and interactive finite difference-based Acheson process (used for the production of silicon carbide).     

火力发电机组蒸汽喷射式抽真空系统节能特性试验研究与分析

蒸汽喷射泵具有抽吸量稳定的特点,使其成为火力发电机组抽真空系统节能改造的一个重要技术方案,本文以某台同时安装了蒸汽喷射式抽真空系统和水环式真空泵的机组为例,详细测量和分析在各种实际运行工况(不同的机组负荷、凝汽器严密性、循环水进水温度)下,与水环式真空泵相比,蒸汽喷射式抽真空系统的节能收益以及对凝汽器换热系数的影响。试验结果表明:当凝汽器严密性非优秀时,与水环式真空泵组相比,蒸汽喷射式抽真空系统能产生一定的节能收益;该收益随凝汽器严密性变差、机组负荷率降低、循环水进水温度升高而增大。蒸汽喷射式抽真空系统改造方案并非适合所有机组,实施前应根据凝汽器抽真空系统实际运行状态核算投资回报周期。     

Studies on the Reduction of Coefficient of Variation: A Case Study

In a spinning mill, yarn is the final product. Linear density expressed in terms of count is one of the important characteristics of yarn. Because variability of textile strands increases as the linear density increases, the variability in the count is often measured in terms of coefficient of variation (CV)%. The yarn with a high CV% of count leads to a higher end breakage rate during the spinning and subsequent weaving/knitting operations, and consequently, results in lesser productivity and poorer appearance quality of the woven/knitted fabric. When this woven/knitted fabric is dyed, uneven shades are generated. Because the production of yarn involves processing of raw cotton in multimachines at multistages, possible sources that lead to a high CV% of count are many. Enrick's (1960) analysis procedure, which is based on the modification of the range method for analysis of variance, is used conventionally for detecting the stages where excessive “between-machine” differences are present. When the CV% of count is inflated due to the generation of systematic variation in any machine or introduction of high variability by any machine, this inflation remains undetected when using Enrick's procedure. The case study presented here demonstrates that a step-by-step analysis of linear densities of different stage-outputs starting from yarn to card sliver, using appropriate nested design models along with Duncan's multiple range test, is very useful in detecting all possible sources of a high CV% of count of yarn.     

基于HTCPN的分段生产物流系统建模与仿真:案例研究

船舶分段生产物流系统是一个典型的资源约束下的多项目调度复杂系统。根据S企业分段生产流程和资源的配置情况,利用层次赋时有色佩特里网(HTCP-net),结合提出的一种适合多项目调度的启发式规则,建立了分段生产物流系统模型。通过CPN tools进行仿真,验证了模型的正确性,发现了流程中的瓶颈,提出了合理的资源配置数量,通过对比证明了本启发式规则较适合船厂的多项目调度。文中的研究方法对复杂的造船流程的建模、仿真和分析具有一定参考价值。     

焊装作业时间标准的制定和生产线再设计:案例研究

对某汽车企业的焊装工艺过程进行了分析,借助模特法建立了焊装作业时间标准。然后通过重新安排各工位的操作对生产线进行了再设计。结果,提高了生产线的平衡度和生产率。例如,其中一条生产线在没有增加操作人员的条件下,生产率提高了36％。     

EEG-BCI实验范式交互界面设计综述研究

随着人工智能在神经科学和人机交互等领域的深度交叉融合,脑-机接口(BCI)再次引起了国内外智能交互领域学者的关注.目的 为了提高脑-机接口系统效率,运用交互设计思维呈现符合被试心理预期的界面形式,减少被试视觉疲劳,更加高效、准确的获取实验数据.方法 对目前基于事件相关电位(ERP)、视觉稳态诱发电位(SSVEP)和运动想象(MI)等EEG-BCI实验范式的交互界面设计进行了详细地梳理和归纳.结论 通过综述为脑-机接口实验范式设计研究提供参考,改善目前EEG-BCI在交互控制领域的应用局限性,提高BCI系统可用性、易用性.更有助于促进工效学、设计学科、认知神经科学、信息科学等多学科的交叉融合,为基于脑-机交互的人工智能发展提供新方向和新思路.