POWDER TECHNOLOGY AND PHARMACEUTICAL PROCESSES

Transcription

1 POWDER TECHNOLOGY AND PHARMACEUTICAL PROCESSES ' fe Edited by DOMINIQUE CHULIA Laboratoire de Pharmacie Galenique, UFR de Pharmacie, Limoges, France MICHEL DELEUIL Rhone-Poulenc Rorer, Antony, France YVETTE POURCELOT Laboratoire de Pharmacie Galenique, UFR de Pharmacie, Dijon, France ELSEVIER Amsterdam - London - New York - Tokyo 1994

2 XV CONTENTS Preface Acknowledgments Contributors VII XI XIII Introduction to part 1 BACKGROUND TO PHARMACEUTICAL ENGINEERING 1 Chapter 1 SAMPLING M. Deleuil 1. Introduction 3 2. Basic discussion Sampling stages Bernoulli's law The distribution function by weight Minimum error The problem of units - some numerical examples Particle analysis Conclusion on the basic approach Sampling practice Collection of M p Static sampling Dynamic sampling Processing of M p to obtain M a Splitting devices to reduce the size of Mp Dividing devices Sampling in less than 100 mg of powder Other operations General discussion Further aspects on the statistical distribution of particles References 25 Chapter 2 PHYSICO-CHEMICAL TRANSFORMATIONS OF POWDERS M. Soustelle 1. Thermodynamic study of transformations Thermal change of solids Phenomena accompanied by changes in local or global composition without creation of new phases, and without textural modification Phenomena accompanied only by textural modifications Phenomena resulting in the creation of new phases 32

3 1.2. Thermodynamic of solid-gas systems Thermodvnamic classification of solid-gas transformations 3D Thermodynamic approach to the phenomena Equilibrium laws and solution models Changes equilibrium conditions with particle size Serial transformations, juxtaposition of ranges of stability Thermodynamics of solid-liquid equilibria Dissolution of a solid with dissociation Dissolution of a solid without dissociation Influence of temperature on solubility Influence of particle size on solubility Adsorption of gases on solids Definition, physical adsorption and chemisorption Thermodynamics aspects of adsorption, shapes of the isotherms The B.E.T. theory and the measurement of specific area The adsorption-desorption cycle, hysteresis, measurement of the porosity of solids Chemisorption isotherms, Langmuir's theory Kinetics of transformations Specific rates and absolute rates Rate of dissolution in a liquid Thermal decompositoion rate of a powder Chemisorption rate References 58 Chapter 3 STRUCTURE AND TEXTURE OF SOLIDS G. Thomas 1. Crystal structure Cry stallographic geometry Cohesion in the crystal structures Polymorphism Determination of crystal structures Structure and physico-chemical properties of the real solid Imperfections Isolated defects Defects with one, two or three dimensions Structure-property relationships The concept of granules From granules to powder From the aggregate to the agglomerate Texture Summary: from the monocrystal to the bulk Determination of textures Physico-chemical methods t. 1. Specific area and porosimetry by adsorption Mercury intrusion porosimetry Physical methods Laser granulometry Sedimentometry Laser diffusion Image analysis Texture control testing 73

4 8. Textures and physico-chemical properties of the real solid Properties related to the surface area Permeability of a porous bed Reactivity of a solid Properties linked to the surface state: wettability Properties due to the surface extent and state: compressibility Conclusion References 78 Chapter 4 SURFACE-ACTIVITY OF WATER J. Yvon, F. Thomas, F. Villieras, L.J. Michot 1. Surface heterogeneity and adsorption mechanisms Hydration of mineral surfaces The reference state: the "dry" solid Hydration at low relative pressures Experimental techniques and data treatment Example of analysis in the case of a swelling solid Hydration of pastes Experimental techniques Determining parameters: salinity, rigidity, humidification-drying cycles Swelling scales Surface charge Origin The electrical double layer Chemical model of surface complexation Experimental determination of the components of the surface charge Potentiometric titration Analysis of the adsorbed counterions Electrokinetic methods Determination of equilibrium constants Graphic extrapolation Simulation Validity of the surface complexation models Exchange capacity Wettability, hydrophilicity-hydrophobicity Definition Case of powdered solids. Relative estimations, comparisons References 108 Chapter 5 PARTICLE AND POWDER DYNAMICS M. Deleuil, D. Chulia, Y. Pourcelot 1. Introduction: choosing the right technology Particle characteristics and particle dynamics Usefulness of size and shape analysis Electrostatic phenomena Background Consequences of electrostatic charges 125

5 Guidelines for the prevention of static electrification Particle dynamics J Particle hydrodynamics Problems in bulk manufacturing processes Powder dynamics and bulk testing Flow } Ideal free-flowing bulk Cohesive powders Wall friction and caking Flow and flow measurements The nature of the forces involved in cohesion and aggregation Flow reliability Hardening Bulk densification Hardening References 160 Chapter 6 MOTION, HEAT AND MASS TRANSFERS C. Laguerie 1. Introduction Motion of particles in a fluid Flow past a cylinder and a sphere Drag coefficients for a spherical particle Terminal falling velocities of spherical particles Pressure drop of a fluid through a packed bed of spherical particles Fluidization of particles The phenomenon of fluidization Minimum fluidizing velocity Entrainment velocity of the particles in paniculate fluidization Heat transfer about solid particles Heat conduction from a sphere to a stagnant fluid Forced convection around a single sphere Forced convection through packed beds Fluid-to-particle heat transfer in a fluidized bed Mass transfer around solid particles References Notations 189

6 Introduction to part 2 POWDERS AND MULTIPHASE PRODUCT PROCESSES 191 Chapter 7 CRYSTALLIZATION R. David and D. Giron 1. Introduction Definitions Solute-solvent system Fractional crystallization Supersaturation Polymorphism and pseudo-polymorphism Importance of controlling polymorphism (some examples) Thermodynamic and kinetic aspects of polymorphism How to solve polymorphism problems? Elementary processes of crystallization Nucleation Primary nucleation Metastability Secondary nucleation Crystal growth Integration rate in the crystal lattice External diffusion flux Global deposition flux Global deposition flux from ionic solutions Ripening Agglomeration Breakage Crystal engineering Crystal morphology and crystal habit Solvent, impurities, additives Modeling of simple crystallizers Mass and energy balances of a crystallizer Population balance of crystals Simple stirred crystallizers Cooling batch crystallizers Evaporation batch crystallizers Mixed solvent mixed product removal (MSMPR) continuous crystallizer Deviations of the MSMPR crystallizer Other industrial crystallizers Multizone crystallizers Fluidized beds Example of controlled batch cooling crystallization Some problems encountered in crystallization processes Conclusion References List of symbols 240

7 XX Chapter 8 DRYING G. Rios, A.L. Raoult-Wack, R. Bentejac and R. Joulie 1- Drying operations G. Rios 1. Introduction General presentation Classification References Dewatering and impregnation soaking processes ("DIS Processes") A.L. Raoult-Wack 1. General presentation Basic principles Effect of the operating variables Conclusion References Freeze-drying R. Bentejac 1. General aspects The stages of freeze-drying Freezing Minimum freezing temperature The rate of cooling Freezing and formulation Freezing processes Sublimation Sublimation temperature Sublimation pressure Secondary drying Freeze-drying methods Preliminary studies and formulation Pilot-scale trials Validation of industrial apparatus Validation of the process Pharmaceutical industry applications of freeze-drying Storage of fragile compounds Properties of the lyophilized solid Conclusion References Fluid bed drying R..Joulie 1. Introduction General design and hydrodynamic properties Heat and mass transfer properties Dryers 276

8 5. Measurements and control in bed-fluidized dryers Advantages and limitations of fluid-beds dryers References 283 Chapter 9 1- STORAGE, FEEDING, PROPORTIONING D. Schulze 1. Storage of bulk solids in silos Flow profiles Silo stresses Flow problems Silo design for flow Design of mass flow silo Funnel flow silo design Application of the results of silo design Mass flow rates Constructional aspects of technical silo design Hopper geometry Discharge devices, feeders Blockage and control units Screw conveyors Belt feeder Rotary valves Vibrating hoppers Vibrating conveyor General review Discharge aids Design precautions Proportioning of bulk solids Discontinuous proportioning Continuous proportioning Volumetric proportioning Gravimetric proportioning References PNEUMATIC CONVEYING P. Hilgraf 7. Pneumatic conveying General principles Conveying diagram, types of flow Solids influences Conveying line design Solid feed systems Dense-phase conveying systems References 346

9 Chapter 10 MIXING J. Bridgwater 1. The field ^47 2. Factors relevant to mixer selection J* 3. Types of powder -^ 4. Mixture quality ;* * 5. Mixing mechanisms for free-flowing systems Physical mixing/segregation mechanisms Use of a modern tracking method Conclusion References 357 Chapter GRANULATION AND COATING Z.D. Ormos 1. Objectives and product forms Mechanisms of bonding and formation Binders and coating materials Physical properties of products Processes and equipment Batch-operated fluidized bed and spouted bed granulators Rotary (centrifugal) fluidization processes Fluidization processes in continuous operation Rolling bed processes Conclusions References MOIST AGGLOMERATION OF PHARMACEUTICAL POWDERS (SIZE ENLARGEMENT OF PARTICULATE MATERIAL), THE PRODUCTION OF GRANULES BY MOIST AGGLOMERATION OF POWDERS IN MIXERS/KNEADERS H. Leuenberger 1. Introduction The dry-blending operation Moist agglomeration process The case of a low viscosity granulating liquid Liquid bridge force and cohesive stress Tensile strength of moist agglomeration, i.e., green granules The power consumption profile Interpretation of power consumption profile Growth kinetics of the agglomerates Scale-up and scale-down exercises / process monitoring Agglomeration process with a high-viscosity binder Conclusion References 389

10 Chapter 12 EXTRUSION/SPHERONISATION J.M. Newton 1. Introduction Formulation of wet powder mass Preparation of extrudate Spheronisation Formulation Assessment of the quality of spheroids References 400 Chapter ASSESSMENT OF POWDER COMPACTION E. Doelker 1. Introduction Transmission of forces through a powder bed Tests on formed compacts Tests and parameters for the mechanical assessment of formed compacts Tests and parameters for mechanical assessment of powders Strain movements and stress relaxation Densification behaviour Work involved in compression Long's compression cycle Frictional parameters Effect of process and formulation variables on the compression parameters Proposed testing procedure Conclusion References TABLETTING - AN INDUSTRIAL VIEW POINT A. Lewis and G. Simpkin 1. Introduction The raw materials The active substance Excipients Process control and scale-up Wet granulation Granule drying Screening, blending and lubrication Compression Tooling for compression machines Concavity, bevels and lettering Shaped punches Compression scale-up Tablet properties Conclusions References 492

11 Chapter NEW PROCESSES - APPLICATION OF SPHERICAL CRYSTALLIZATION TO PARTICULATE DESIGN OF PHARMACEUTICALS FOR DIRECT TABLETTING AND COATING, AND NEW DRUG DELIVERY SYSTEMS Y. Kawashima 1. Introduction Solvent systems for spherical crystallization Preparation of spherically agglomerated crystals for direct tabletting or coating Preparation of drug delivery devices (microcapsule, microsponge, microballoon, nanosphere) Preparation of microcapsules for masking bitter taste Preparation of controlled release Ibuprofen microsponge suspension Preparation of multiple unit hollow microsphere (microballoon) as a floating controlled drug delivery system in the stomach Preparation of DL-lactide/glycolide copolymere nanocapsules by a novel spontaneous emulsification solvent diffusion methods References MICROENCAPSULATION PROCESSES FOR THE MANUFACTURE OF SYSTEMS PROVIDING MODIFIED RELEASE OF THE ACTIVE CONSTITUENT H. Porte and G. Couarraze 1. Introduction Formulation systems and agents Diffusion systems Erodible systems Encapsulation methods Physico-chemical processes Coacervation processes Encapsulation by emulsion-solvent evaporation Microencapsulation by melting solidification Chemical microencapsulation Microencapsulation by interfacial polymerization Microencapsulation by polymerization in suspension or emulsion Microencapsulation by spraying Spray-coating Encapsulation by atomization or spray-drying Encapsulation by prilling Conclusions Sophistication of the systems Development of non-pharmaceutical modified-release forms References 538

12 Chapter 15 DISSOLUTION AND POWDFLR TECHNOLOGY W.A. Hanson 1. Introduction Formulation objectives Powder selection fundamentals Physical differences affecting dissolution Particle size and shape Flowability Mixing Moisture and hygroscopic index Examples of dissolution problems associated with powder specifications Flowability Molecular level stability Moisture Summary References 551 TENTATIVE CONCLUSIONS 553 M. Deleuil