Pharmaceutical Blending and Mixing E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 990

Veröffentlichungsjahr: 2015

Beschreibung

Written in four parts, this book provides a dedicated and in-depth reference for blending within the pharmaceutical manufacturing industry. It links the science of blending with regulatory requirements associated with pharmaceutical manufacture. The contributors are a combination of leading academic and industrial experts, who provide an informed and industrially relevant perspective of the topic. This is an essential book for the pharmaceutical manufacturing industry, and related academic researchers in pharmaceutical science and chemical and mechanical engineering.

Leseprobe

CONTENTS

Cover

Title page

Contributor List

Preface

Pharmaceutical Blending and Mixing: Role, Challenges and Trends

Part I: Fundamentals of Mixing

1 Mixing Theory

1.1 Introduction

1.2 Describing Mixtures

1.3 Scale of Scrutiny

1.4 Quantifying Mixedness for Coarse and Fine-Grained Mixtures

1.5

Determining the End-Point of Mixing:

Comparison of Mixing Indices

1.6 Continuous Flow Mixers

References

2 Turbulent Mixing Fundamentals

2.1 Introduction

2.2 The Velocity Field and Turbulence

2.3 Circulation and Macro-Mixing

2.4 Fully Turbulent Limits and the Scaling of Turbulence

2.5 The Spectrum of Turbulent Length Scales, Injection of a Scalar (Either Reagent or Additive) and the Macro-, Meso- and Micro-Scales of Mixing

2.6 Turbulence and Mixing of Solids, Liquids, and Gases

2.7 Specifying Mixing Requirements for a Process

2.8 Conclusions

Notation

References

3 Laminar Mixing Fundamentals

3.1 Laminar Flows

3.2 Mixing in Laminar Flows

3.3 Recent Advances

References

4 Sampling and Determination of Adequacy of Mixing

4.1 Introduction, Process Understanding, and Regulations

4.2 Theory of Sampling

4.3 Sampling of Pharmaceutical Powder Blends

4.4 Stratified Sampling Approach

4.5 Testing

4.6 Process Knowledge/Process Analytical Technology

4.7 Real Time Spectroscopic Monitoring of Powder Blending

4.8 Looking Forward, Recommendations

4.9 Conclusion

4.10 Acknowledgments

References

Part II: Applications

5 Particles and Blending

5.1 Introduction

5.2 Particle Geometry

5.3 Particle Interactions

5.4 Empirical Investigations of Particles and Blending

5.5 Simulation Techniques

References

6 Continuous Powder Mixing

6.1 Introduction

6.2 Overview

6.3 Theoretical Characterization

6.4 Experimental Characterization

6.5 Continuous Mixing Efficiency

6.6 Effects of Process Parameters on Mixing Behavior and Performance

6.7 Mixing Performance

6.8 Conclusions and Continuing Efforts

References

7 Dispersion of Fine Powders in Liquids: Particle Incorporation and Size Reduction

7.1 Particle Incorporation into Liquids

7.2 Break Up of Fine Powder Clusters in Liquids

References

8 Wet Granulation and Mixing

8.1 Introduction

8.2 Nucleation

8.3 Consolidation and Growth

8.4 Breakage

8.5 Endpoint Control

References

9 Emulsions

9.1 Introduction

9.2 Properties of Emulsions

9.3 Emulsion Stability and Surface Forces

9.4 Principles of Emulsion Formation

9.5 Emulsification Equipment

9.6 Concluding Remarks

Nomenclature

Greek symbols

References

10 Mixing of Pharmaceutical Solid-Liquid Suspensions

10.1 Introduction

10.2 Scale-Up of Operations Involving Solid Suspensions

10.3 General Principles of Solid-Liquid Suspensions

10.4 Solids Charging

10.5 Solid Suspension

10.6 Solid Distribution

10.7 Blending in Solid-Liquid Systems

10.8 Mass Transfer

10.9 Size Reduction, Deagglomeration and Attrition

Nomenclature

Greek symbols

Abbreviations

References

Part III: Equipment

11 Powder Blending Equipment

11.1 Introduction

11.2 Blending Mechanisms

11.3 Blend Time

11.4 Fill Level

11.5 Segregation

11.6 Powder Processing Difficulties

11.7 Blender Classification

11.8 Continuous Blenders

11.9 Blender Selection

11.10 Equipment Specifications

References

12 Fluid Mixing Equipment Design

12.1 Introduction

12.2 Equipment Description

12.3 Measurements

12.4 Mixing Classifications

12.5 Mechanical Design

12.6 Static Mixers

12.7 Challenges and Troubleshooting

Nomenclature

Greek

References

13 Scale-Up

13.1 Introduction

13.2 Similarity and Scale-Up Concepts

13.3 Testing Methods

13.4 Observation and Measurement

13.5 Scale-Up Methods

13.6 Summary

Nomenclature

Greek

References

14 Equipment Qualification, Process and Cleaning Validation

14.1 Introduction

14.2 Blending Equipment Commissioning and Qualification

14.3 Blending and Mixing Validation

14.4 Blending Cleaning Validation

14.5 Conclusion

14.6 Acknowledgements

References

Part IV: Optimization and Control

15 Process Analytical Technology for Blending

15.1 Introduction

15.2 Chemometrics and Data Management

15.3 Near-Infrared Spectroscopy (NIRS)

15.4 Raman Spectroscopy (RS)

15.5 Image Analysis

15.6 LIF Spectroscopy

15.7 Effusivity

15.8 Other Potential Sensor Technologies

15.9 Comments on PAT in Liquid Formulation Mixing

References

16 Imaging Fluid Mixing

16.1 Introduction

16.2 Point Measurement Techniques

16.3 Photographic Imaging

16.4 Digital Particle Image Velocimetry

16.5 Magnetic Resonance Imaging

16.6 Positron Emission Particle Tracking Imaging

16.7 Electrical Process Tomography

References

17 Discrete Element Method (DEM) Simulation of Powder Mixing Process

17.1 Introduction to DEM and its Application in Pharmaceutical Powder Processing

17.2 DEM Simulation of Powder Mixing

17.3 Validation and Comparison with the Experiments

17.4 Concluding Remarks

References

Index

End User License Agreement

List of Tables

Chapter 01

Table 1.1 Definitions of mixing indices from the literature for use with particulate systems

Chapter 03

Table 3.1 Advanced approaches to track particles and visualize mixing and segregation of granular material

Chapter 04

Table 4.1 Description of 2 kg lot mass prepared before mass reductions to get either 100 or 125 g in the final sample, depending on the nature of the method or device [9]

Table 4.2 Requirements for dosage units obtained from stratified sampling locations. All results are weight corrected

Chapter 08

Table 8.1 Summary of granule attributes

Chapter 09

Table 9.1 Volumetric drop size distributions calculated according to the algorithm in equations 9.5–9.8

Table 9.2 Different definitions of mean drop size

Chapter 10

Table 10.1 An overview of equipment used in drug substance processing across a range of scales

Table 10.2 Common solid-liquid mixing duties and their scale-up rules (the scale-up rules are explained in more detail in subsequent sections)

Table 10.3 Typical solid liquid operations and their relevant duties

Table 10.4 Illustration of power requirement for different suspension criteria and settling velocities (adapted from Oldshue, 1983)

Table 10.5 Definition of Kolmogorov scales and typical values in turbulent water

Table 10.6 Turbulent forces on particles in water

Table 10.7 Values of the Zwietering constant S for different impellers and mixer configurations

Chapter 11

Table 11.1 Bulk densities of some powders

Chapter 12

Table 12.1 Metal alloy compositions (percentages)

Table 12.2 Surface finishes before and after electropolishing

Table 12.3 Standard motor sizes (metric and horsepower)

Table 12.4 Number of static mixer elements

Chapter 13

Table 13.1 Scale-exponents

Table 13.2 Geometric similarity scale-up example

Table 13.3 Non-geometric scale-up example – single impeller steps

Table 13.4 Non-geometric scale-up example – dual impeller steps

Table 13.5 Non-geometric scale-up example – alternate impeller design

Chapter 15

Table 15.1 PAT realistic opportunities in pharmaceutical production “unit operations”

Table 15.2 Comparative study of NIR blend analysis. Reprinted with permission from EPR, Real-Time NIR Monitoring of Pharmaceutical Blending Process with Multivariate Quantitative Models by N. Abatzoglou et al., 5, 57–67. Copyright (2005) Russell Publishing Co.

Chapter 17

Table 17.1 The modelling conditions for the sensitivity analysis on size using DEM simulation (Hassanpour et al., 2011)

List of Illustrations

Chapter 01

Figure 1.1 Idealized mixtures of 50% white and 50% black particles (a) non-random perfect mixture, (b) number of white particles in each 4 × 4 sample of the non-random mixture (c) random mixture and (d) number of white particles in each 4 × 4 sample of the random mixture

Figure 1.2 The effect of decreasing the scale of scrutiny on the perceived quality of the mixture

Figure 1.3 (a) a coarse-grained mixture and (b) a fine-grained mixture

Figure 1.4 The effects of changing scale and intensity of segregation on the quality of the mixture

Figure 1.5 An illustration of the calculation of the autocorrelation function for a mixture

Figure 1.6 The autocorrelation function for a mixture showing the definition of the length scale of segregation

Figure 1.7 The effect of the scale of scrutiny on the intensity and length scale of segregation for a fully random mixture (lengths scales are multiples of the particle size)