基于有限元技术的片剂压制过程研究

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摘要

片剂是使用最为广泛的剂型之一，因为其携带方便、易于服用。但片剂生产

过程中时常会出现裂片、松片、溶出度不稳定等问题，影响片剂质量。本文采用

有限元模拟与实验研究相结合的方法，探讨粉末在不同条件压片过程下片剂内部

密度分布、应力分布、片剂重量、硬度、孔隙率等指标。主要研究内容和结论如

下：

1、采用有限元模拟的方法，选用 Drucker-Prager/Cap 模型对不同压片方式、

不同片剂形状、不同摩擦情况、不同上下冲加压速度的压片过程进行了分析，讨

论了片剂内密度分布、等效应力分布和轴向位移量等指标。结果显示，加压时片

剂顶部径向上外端的密度始终比中心区域高；解压时片剂会发生弹性回复的现象，

使得片剂出现膨胀，顶部通常比底部弹性回复的程度更高；双向压片的相对密度

差比单向压片小，均匀性更好；模具润滑不足时，粉末与中模内壁间产生较大摩

擦，阻碍了粉末顺畅地流动；片剂内部相对密度差随着上下冲加压速度增大而增

大。

2、采用实验研究的方法，制得直径为 9.0mm、目标片厚为 3.2mm 和3.0mm

的平面圆片，得到转台转速分别为 10、20、30、35rpm 时的片重差异、硬度等指

标。另外制得直径为 9.5mm、目标片厚为 4.3mm 和3.8mm 的标准形凹面圆片，得

到转台转速分别为 25、30、35rpm 时的片重差异、硬度等指标。实验结果显示平

面圆片的片剂重量和硬度均随着转台转速的递增而减小，标准形凹面圆片的片剂

重量和硬度与转台转速暂未发现直接关系。对转台转速 25、35rpm 时压制的标准

形凹面圆片和转台转速为 20、30rpm 时压制的平面圆片进行 Micro-CT 扫描及二维

重构，得到了扫描图像及各截面的重构图像，但区别不明显，再取上中下三个截

面进行比较。实验表明：不同转台转速下所得片剂内部孔隙率不同。并初步判断

为：降低转台转速有助于减少片剂的孔隙率。

转台转速的增加也就意味着上下冲加压解压速度增加，因此将有限元模拟和

实验研究联系起来，初步得出以下结论：转台转速越大，则片剂相对密度差值越

大，粉末内密度分布均匀性降低，片剂硬度降低，各截面孔隙率增大，片剂的综

合性能降低，因此有限元模拟和实验结果具有一致性。实际生产中既要保证一定

的生产效率，也要采用合理的转台转速。

关键词：转台转速 Drucker-Prager/Cap 模型密度分布硬度

ABSTRACT

The tablet is one of the most common and popular dosage form in the

pharmaceutical industry. Tablets are convenient for patients since they are portable and

easy to be administered. But some defects, i.e. cracks and fracture of powder compacts

and unstable drug release, are likely to be induced in tablet processing, which affects

tablet quality. Thus, the objective of this study is to provide a fundamental

understanding of the mechanical behavior of pharmaceutical powders during

compaction, such as internal density distribution, stress distribution, tablet weight,

crashing strength and porosity. Again, a combined investigation including experimental

and numerical analyses has been carrid out. Following work has been carried out:

Compaction tests of Drucker-Prager/Cap model for lactose powder were simulated

by finite element method (FEM) to get the information of density distribution, mises

distribution and particles displacement under different conditions, which included

different compaction profiles, different tablet shapes, different lubrication conditions

and different compaction speeds. The numerical analysis results showed that during

decompression, the compaction pressure dropped quickly as the distance between the

two punches increased, and some of the elastic strain induced during compression

recovered. This was accompanied by an increase in the volume of the powder bed and a

consequent decrease in the relative density; Double-ended compaction was better than

single-ended compaction to get more uniform compacts; The lubrication condition

could reduce the adverse effects caused by the particles displacement lag effect induced

by the die wall friction; The higher compaction speed was easy to get a powder compact

with more uneven density distribution.

In experiments, two shapes of tablets were produced by two kinds of rotary tablet

presses. The operational parameters were 10,20,30,35rpm of die table rotational speeds

for 9.0mm flat-faced tablets and 25,30,35rpm of die table rotational speeds for 9.5mm

standard convex tablets. The experiments results suggested that the weight and crashing

strength of the flat-faced tablets were decreasing with the increasing die table rotational

speed. But the changing of weight and crashing strength of standard convex tablets were

not founded to be related to die table rotational speed. The inner microstructural

characteristics of tablets were discussed deeply using Micro-CT technique. Tablets were

taken as samples for Micro-CT scanning and cross-section images were obtained with

scanning images by reconstructing. The difference among those samples weren't distinct

comparatively. The porosity under different compaction speeds were obtained. Tablet

slices with various shapes (flat-faced and standard convex tablets) were produced under

different die table rotational speeds respectively, then the porosity were obtained in the

same method. The experimental results demonstrated that a distinctive variety in

porosity was found according to different die table rotational speeds. It was initially

estimated that the quicker die table rotational speeds were, the bigger porosity existed.

Actually the quicker die table rotational speeds, the faster compaction speed of

upper and lower punch. When die table rotational speed was improving, tablet relative

density difference was more obvious and density distribution became nonuniform. The

crashing strength of tables were lower, the porosity were bigger, which influenced the

performance of the tablets. So the results of experiments and numerical simulations

were consistent. It is necessary to guarantee both certain efficiency and reasonable die

table rotational speed.

Key Words: die table rotational speed, Drucker-Prager/Cap model,

density distribution , crashing strength

中文摘要

ABSTRACT

第一章绪论 .............................................................................................................1

§1.1 引言 ..............................................................................................................1

§1.2 粉末压片工艺研究现状 ...............................................................................2

§1.2.1 国外研究进展 ......................................................................................2

§1.2.2 国内研究进展 ......................................................................................4

§1.3 粉末压片数值模拟研究 ...............................................................................4

§1.4 Micro-CT 技术扫描技术及其应用 ................................................................5

§1.5 研究的主要内容及意义 ...............................................................................6

第二章粉末压片的理论分析 ..................................................................................8

§2.1 粉末压片成形过程分析 ...............................................................................8

§2.2 材料模型分析 ...............................................................................................8

§2.2.1 金属塑性力学方法 ..............................................................................9

§2.2.2 广义塑性力学方法 ..............................................................................9

§2.3 Drucker-Prager/Cap 模型 ............................................................................. 10

§2.3.1 剪切屈服面 ........................................................................................ 10

§2.3.2 帽子屈服面 ........................................................................................ 11

§2.3.3 流动法则 ............................................................................................ 12

§2.3.4 模型参数的获取 ................................................................................ 12

§2.4 本章小结................................................................................................... 13

第三章粉末压片有限元模拟技术研究 ................................................................. 14

§3.1 ABAQUS 软件及模拟过程简介 .................................................................. 14

§3.1.1 ABAQUS 软件简介 .......................................................................... 14

§3.1.2 ABAQUS 软件使用步骤 ................................................................... 15

§3.2 建模、材料定义及网格划分 .................................................................... 16

§3.3 接触分析................................................................................................... 17

§3.4 粉末与模壁间的摩擦分析 ........................................................................ 18

§3.5 边界条件与载荷 ....................................................................................... 19

§3.6 本章小结................................................................................................... 19

第四章粉末压片过程模拟 .................................................................................... 20

§4.1 相对密度分析 ........................................................................................... 20

§4.2 弹性回复分析 ........................................................................................... 22

§4.3 不同压片方式下的粉末压片 .................................................................... 24

§4.4 不同片剂形状的粉末压片 ........................................................................ 25

§4.5 不同摩擦状况下的粉末压片 .................................................................... 26

§4.6 不同压片速度的粉末压片 ........................................................................ 28

§4.7 本章小结................................................................................................... 30

第五章压片过程实验研究 .................................................................................... 31

§5.1 实验理论基础 ........................................................................................... 31

§5.1.1 重量差异 ............................................................................................ 31

§5.1.2 片剂硬度 ............................................................................................ 31

§5.1.3 灰度值 ................................................................................................ 31

§5.1.4 孔隙率 ................................................................................................ 32

§5.2 实验设备 ................................................................................................... 32

§5.2.1 压片机 ................................................................................................ 32

§5.2.2 Micro-CT ........................................................................................... 34

§5.3 实验材料 ................................................................................................... 36

§5.4 实验方法 ................................................................................................... 36

§5.4.1 压片机压片 ........................................................................................ 36

§5.4.2 片剂的 Micro-CT 扫描 ...................................................................... 37

§5.5 实验结果 ................................................................................................... 39

§5.5.1 片重差异 ............................................................................................ 39

§5.5.2 硬度 ................................................................................................... 40

§5.5.3 Micro-CT 扫描结果 ............................................................................ 42

§5.6 本章小结 ................................................................................................... 44

第六章总结与展望 ................................................................................................ 46

参考文献 ................................................................................................................. 48

在读期间公开发表的论文和承担科研项目及取得成果 ....................................... 52

致谢 ......................................................................................................................... 53

第一章绪论

压片技术已经在很多领域被广泛地应用。比如加工金属和陶瓷材料第一步通

常是由粉末先压片制成生坯体，然后再经高温烧结成形。在化学制品领域，洗衣

用的片状洗涤剂由干粉压片而成。在制药行业，每天超过十亿的片剂都在压片机

中制成[1]。药用剂型中最常见的一种剂型就是片剂[2]。和其他剂型相比较，片剂具

有成本低廉、便于服用者较长时间保存、不容易受到温度和湿度的影响、服用方

便等诸多优势。在压片过程中，经常会遇到裂片、粘片、松片、迭片、粘冲、冲

模断裂、片重差异等问题。这些问题不仅影响到片剂的外观形状，而且还直接影

响到内在质量，因而药物粉末压片技术吸引了广大研究人员和生产者的关注。由

于粉末压片成形过程非常复杂，所以详细了解片剂制备时粉末致密化、密度变化

与分布规律、粉末变形特征成为一个难题，而有限元数值模拟技术的发展和应用

为进一步了解粉末压片成形过程提供了有效和快速的工具。

§1.1 引言

制药工业中，片剂的制备工艺主要有干法制粒压片、湿法制粒压片和粉末直

接压片等几种。前两者均是将制得的颗粒进行压片，后者是不经过制粒直接把药

物和辅料混合物进行压片的方法。目前国内使用最广泛的是湿法制粒压片，其机

理为在药物和辅料粉末中加入黏合液制成软材，再将湿颗粒烘干去湿后制成干颗

粒送入压片机压片。该工艺优点为颗粒质量好、外形美观、压缩成型性好。缺点

是制造过程比较复杂，步骤较多，生产效率较低。干法制粒是将药物与辅料的混

合粉末用较大压力压缩制较大粒状或片状物后，再粉碎成所需大小的颗粒并对其

进行压片。该工艺优点是能制造对湿热敏感的药物，但是仍旧避免不了制粒过程[3]。

粉末直接压片法是将药物的粉末与适宜的辅料分别经过筛选、混合后直接压缩成

片。使用这种方法的优点是制作过程无需制粒，因此节能省时，尤其适合对湿热

敏感的药物制备，但缺点是存在粉末流动性差、片重差异大、易裂片等问题，使

得该工艺的应用受到一定限制。目前在国外应用较多，国内较难推广，原因是优

质辅料的缺乏，导致生产中粉尘较多，国产压片机精度不够理想，容易产生漏粉

等。

对于片剂生产中产生的一些裂片、松片、片重差异不合要求等问题，Han[4]在

文中指出 Burlinson 和Long 等研究人员用较简单的理论定性分析了它们产生的原

因。在计算机技术应用以前，除大量的实验研究外，其理论分析是将问题做一定

的简化、假设，最后归结为在给定边界条件下求解其控制方程（常微分方程或偏

微分方程）。对于这些方程若用解析的方法进行求解，只有在极少数的特殊情况下

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摘要：

摘要片剂是使用最为广泛的剂型之一，因为其携带方便、易于服用。但片剂生产过程中时常会出现裂片、松片、溶出度不稳定等问题，影响片剂质量。本文采用有限元模拟与实验研究相结合的方法，探讨粉末在不同条件压片过程下片剂内部密度分布、应力分布、片剂重量、硬度、孔隙率等指标。主要研究内容和结论如下：1、采用有限元模拟的方法，选用Drucker-Prager/Cap模型对不同压片方式、不同片剂形状、不同摩擦情况、不同上下冲加压速度的压片过程进行了分析，讨论了片剂内密度分布、等效应力分布和轴向位移量等指标。结果显示，加压时片剂顶部径向上外端的密度始终比中心区域高；解压时片剂会发生弹性回复的现象，使得片剂出现膨胀，...

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