Pharmaceutical Dosage Forms: Capsules

 

Description:

Pharmaceutical Dosage Forms: Capsules covers the development, composition, and manufacture of capsules. Despite the important role that capsules play in drug delivery and product development, few comprehensive texts on the science and technology of capsules have been available for the research and academic environments. This text addresses this gap, discussing how capsules provide unique capabilities and options for dosage form design and formulation.

 

 

Table of Contents:

 

Chapter 1 Advances in Capsule Formulation Development and Technology

Alternative Shell Compositions

Unique Drug Delivery Systems

Liquid and Semisolid Capsule Filling

Using Capsules to Manage Poorly Soluble Drugs

Systematic Approaches for Understanding Hard Shell Capsule Formulation and Filling

Modeling of Plug Formation

Modeling in Support of Formulation Development

Multivariate Analysis and Response Surface Methodology

Expert Systems

Neuro-Nets (NNs)

References

Chapter 2 An Introduction to Two-Piece Hard Capsules and Their Marketing Benefits

Introduction

Market Growth of Two-Piece Hard Capsules

Historical Development of the Capsule Dosage Form

Capsule Shell Manufacturing Process

Gelatin Solution Preparation

Capsule Shell Production

Quality Control

Capsule Materials

Gelatin

Hypromellose

Capsule Shell Features (Capsule Design)

Capsule Sizes

Capsule Colorants and Printing

Brand Image and Marketing

Patient Acceptance

Moisture Content and Storage

Capsule Fill Materials

Powders

Granules

Pellets

Minitablets

Tablets

Liquid and Semisolids

Dosing of Pure API

Dry Powder Inhalers

Benefits of Marketing Two-Piece Capsules

References

Chapter 3 Hard Shell Capsules in Clinical Trials

Introduction

Preclinical Phase

Clinical Phase

Miniaturization Technology

Xcelodose Technology

Capsule Design and Specialty Shells

Hard Gelatin Capsules PCcaps

Coni-Snap Hard Gelatin Capsules

Hard Gelatin DBcaps

Hypromellose (HPMC) Capsules

Comparison of HPMC and Hard Gelatin Encapsulation and Performance

Plantcaps

Starch Capsules

Specialty Shells Design for Targeted Drug Delivery

PIC Technology

Impermeable or Coated Hard Gelatin Encapsulation and Pulsatile Delivery

Fused and Banded Hard Gelatin Capsules

Acid-Resistant HPMC Capsules

Gastro-Resistant (Enteric-Coated) HPMC Capsules

Coated Hypromellose Capsules

Enteric-Coated Starch Capsules

Targit Technology

Osmotic Capsules

Clinical Batch Manufacturing or Fabrication of Hard Gelatin Capsules

Miniaturization Technology Encapsulation

Liquid or Semisolid Filled Hard Gelatin Capsules

Overencapsulation Hard Gelatin Capsules (DBcaps)

Manufacturing Considerations of DBcaps and Clinical Trials

Encapsulated Polyherbal Formulations and Clinical Trials

Hard Shell Capsules and Targeted Oral Drug Delivery

Stomach

Intestine

Colon

Peptide/Protein Colonic Delivery in Hard Shells

Hard Gelatin Capsules and Chronotherapy

Encapsulated Lipid-Based Formulations and Clinical Trial Relevance

Drug Release Mechanisms and Hard Shell Encapsulation

Matrix Capsular Systems

Reservoir Capsular Systems

Osmotic Systems

Pulsatile Release Systems

QbD Approach and Encapsulation for Clinical Trials

Overview

Elements of QbD in Development of Capsules for Clinical Trial

Drug and Excipient Characteristics

Manufacturing Process and Process Control

Powder Blending

Capsule Filling

CQA and Risk Assessment

Finished Capsule Attributes

Implementation of QbD in Hard Shell Capsule Formulation for Clinical Trials

In Vitro and In Vivo Performance of Hard Shell: Regulatory Perspectives

In Vitro– In Vivo Performance

Capsules versus Tablets

Capsule versus Granules

Capsules versus Suspensions

Regulatory Perspectives on Dissolution and In Vivo Release from Hard Shells

Conclusions

References

Chapter 4 Capsule Shell Manufacture

Introduction

Hard Capsules

Early Development of Process and Machines

Capsule Shell Design

Manufacture of Hard Gelatin Capsule Shells

Preparation of the Manufacturing Solutions

Formation of Hard Capsule Shells

Capsule Sorting

Capsule Printing

Packaging and Storage

Hard Capsule Quality

Modern Hard Capsule Manufacturing Machines

Gelatin Alternatives for Hard Capsule Manufacture

Alternative Methods of Manufacture

Soft Capsules

Early Development of Process and Machines

Manufacture of Soft Gelatin Capsules

Preparation of Gelatin Manufacturing Solutions and Fill Formulations

Manufacture of Seamed Soft Gelatin Capsules with Liquid Products

Manufacture of Seamed Soft Gelatin Capsules with Different Properties

Manufacture of Seamed Soft Gelatin Capsules with Dry Products

Manufacture of Seamless Soft Capsules

Seamed Modified-Gelatin Capsules

Soft Capsule Quality

Gelatin Alternatives for Soft Capsule Manufacture

Manufacture of Non-Gelatin Soft Capsules

Seamless Non-Gelatin Capsules

Acknowledgment

References

Chapter 5 Non-Gelatin-Based Capsules

Introduction

Two-Piece Hard Capsules and Their Manufacturing

HPMC (Hypromellose)-Based Capsules

HPMC Capsules for Immediate Release

HPMC Capsule Manufacturing

Physicochemical Properties

Dissolution and Disintegration

In Vivo Performance of HPMC Capsules

Special Applications of HPMC Capsules

Coating of HPMC Capsules

HPMC Capsules for Dry Powder Inhalation

Conclusion

HPMC Capsules for Delayed Release

Introduction

In Vitro Dissolution of Delayed-Release Capsules

In Vivo Performance of Delayed-Release Capsules

Conclusion

Pullulan-Based Two-Piece Capsules

Introduction

Pullulan Capsule Properties

In Vitro Dissolution

In Vivo Performance

Conclusion

Investigational Non-Gelatin Polymer Capsules

Hard Capsules

Soft Capsules

Conclusion

Applications of Non-Gelatin-Based Capsules

Acknowledgment

References

Chapter 6 Hard Shell Capsule Filling Machines

Introduction

Operations Common to All Capsule Filling Machines

Feeding and Rectification

Separation

Filling

Joining and Ejection

Capsule Filling Machine Dosing Systems

Powders

Auger Fill Method

Mechanical Vibration Filling Method

Dosator Method

Tamping Pin/Dosing Disc Method

Drum Filler Method

Compression Filling Method

Beads and Granules/Pellets

Direct Fill

Vacuum Dosator Method

Dosing Chamber

Dosing Disc Method

Tablet and Capsule Overencapsulation

Capsules

Tablets

Liquids/Semisolids

Multicomponent Dosing

Capsule Filling Machinery

Hand-Operated Filling Devices

Semiautomatic Capsule Filling Machines

Fully Automatic Capsule Filling Machines

GKF 2500 ASB 100%—Bosch Packaging Technology

Modu-C—Harro Höfliger

ADAPTA—IMA ACTIVE Solid Dose Solutions

Planeta—MG2

LIQFILsuper80—Qualicaps

AF 200T—ACG-pam

Specialty Fillers

Mettler Quantos QB5

Capsugel Xcelodose

OmniDose

Powdernium Powder Dispensing Workstation

Sealing Technology and Machines

Banding Machines

Qualicaps Band Sealing Machines—HICAPSEAL 40/100 Fully Automatic Hard Capsule Sealing Machines

Qualicaps Lab-Scale Filling/Sealing Machine FS3

S-1 Benchtop Capsule Band-Sealer [Schaefer Technologies, Qualicaps]

Hermetica Capsule Banding Machine [IMA]

Dott.Bonapace BD-3000

Liquid Sealing Machines

cfs 1200

cfs 1500 C

LEMS 70

Ultrasonic Welding of Capsule-Based Systems

Capsule Inspection

Visual Inspection

Vision Systems

Viswill PAPPIS (Plug and Play Portable Inspection System)

CPT INSIGHT 100

InspeCaps 150 by Proditec

Qualicaps CES-150 Capsule Inspection Machine

Other Capsule Support Equipment

Capsule Checkweighers

Bosch KKE 3800

Harro Höfliger OmniControl, Mid-Speed

MG America Anritsu KW9001AP

Capsule Polishers

Brush Polishers

Air Selection Unit

Capsule Separators

Acknowledgments

References

Chapter 7 Instrumented Automatic Capsule Filling Machines and Filling Machine Simulation

Instrumented Capsule Filling Machines

Transducers

Location of Transducers and Site Modification

Wheatstone Bridge

Installation of Gauges

Signal Retrieval from Rotating Components

Calibration

Monitoring/Data Handling

Application of Instrumented Automatic Capsule Filling Machines in Research and Development

Dosator Machines

Dosing Disc Machines

Automatic Filling Machine Simulation

References

Chapter 8 Dry-Fill Formulation and Filling Technology

Introduction

Biopharmaceutical Aspects for Capsules

Formulation Principles for Dry-Fill (Powder) Formulation

Filling Technology

Automatic Capsule-Filling Machines

Auger Fill Principle

Vibratory Fill Principle

Piston-Tamp Principle

Formulation Requirements for Plug-Forming Automatic Capsule-Filling Machines

Flowability

Lubricity

Compressibility, Compactibility, and Cohesiveness

Role of Density in Predicting Capsule Fill Weight

Filling of Granulations into Hard Shell Capsule

Considerations in Scaling-up of Powder-Filled Hard Shell Capsule Formulation

Direct Fill of API (or What Is Referred to as “Powder-in-Capsule”) without Excipients

Practical Considerations in Filling of Pellets into Hard Shell Capsule

Practical Considerations in Filling of Tablets into Hard Shell Capsule

Practical Considerations in Filling of Granules, Pellets, Tablets, and/or Combinations into Hard Shell Capsule

References

Chapter 9 Plug Formation

Introduction

Plugs versus Tablets

Geometry

Density and Porosity

Compression Pressure Used in Development and Manufacture

Axial Force Transmission Ratio

Ejection Forces

Rates of Compression and Ejection

Mechanical Strength

Low-Pressure Compression

Modeling of Low-Force Compression

Angle of Internal Flow

Compaction Constant T according to Mohammadi and Harnby

Two-Phase Densification Model according to Hauer et al.,

Parameterization Using the Kawakita Equation,

Low-Force Compression Model Proposed by Chowhan and Chow

Heckel Equation,

Cooper–Eaton Relationship

Other Approaches That Could Be Used to Model Low-Force Compression

Densification Simulations Using DEM

Stable Arch Formation and Its Significance in Capsule Filling

Particle Deformation during Capsule Filling

Conclusion

Acknowledgment

List of Symbols

References

Chapter 10 Modeling Powder Filling during Encapsulation

Introduction

Encapsulation Methods and Principles

Manual and Semiautomatic Methods

Automatic Methods

Modeling/Powder Fill Estimation during Encapsulation

Estimations in Manual Capsule Filling

The Need for a Dosator-Based Model—A Case Study

Estimations in Dosator-Based Capsule Machines

Powder Densification inside a Dosator

Precompression Densification Factor (f 1(ρ))

Compression Densification Factor (f 2(ρ))

Piston Movement within a Dosator

The Spring Factor

Powder Compressibility

Summary of Model Parameters

Experimental Evaluation of the Model

Machine Differences

Practical Applications of the Model

Case I—BI 671800 Development

Case II—Development of a New Drug Product for Phase I Clinical Studies

Case III—Development of a Generic Drug Product

Case IV—Sticking onto Dosator Pins

Model Challenges

Speed Effects

Induced Densification of Powder Bed

Powder Bed Aeration with Time

References

Chapter 11 Scale-Up and Transfer of Hard Shell Formulations across Machine Types

Introduction

Scaling Up within the Same Design and Operating Principle

Regulatory Meaning of Same Design and Operating Principle

Scaling Up within the Same Subclass

Transferring between Dosator and Dosing Disc Machines

Bulk Powder Properties

Bulk Density and Densification

Compactibility

Flowability

Lubricant Requirements

Dissolution Outcomes

Granulations

References

Chapter 12 Modified-Release Delivery SystemsExtended-Release Capsule Platform

Introduction

Capsules as a Carrier Platform for Oral Extended-Release Drug Delivery

Modified-Release Dosage Forms

Terminology and Definition of Modified-Release Dosage Forms

Dissolution Rate of Drug from Drug Particles, Pellets, or from Various Modified-Release Formulations and Delivery Systems Encapsulated in a Capsule Shell as a Delivery Carrier

Operating Release Mechanisms Associated with Different Encapsulated Modified-Release Dosage Forms

Mathematical Models to Describe Release Kinetics from Extended-Release Capsules Containing Formulated Delivery Systems

Types of Blood Levels for Different Therapeutic Effects

Examples of Commercially Available Hard Shell Extended-Release Capsule Delivery Systems

Encapsulated Matrix Tablets for Extended Drug Release

Encapsulated Coated and Uncoated Pellets for Extended Drug Release

Encapsulated Enteric-Coated Pellets and Enteric-Coated Mini-Tablets for Delayed Release and/or Delayed Extended Release

Encapsulated Beads of a Polypeptide Linaclotide for Once-a-Day Oral Administration

Encapsulated Drug Formulation for Time-Delayed and Targeted Delivery during Drug Development Phases and Research to Assess Drug Absorption

Port System

Egalet

Electronic Capsule Devices for Site-Specific Determination of the Drug Absorption

IntelliCap device

Endoscopy Camera Capsules

Summary

References

Chapter 13 Analytical Testing and Evaluation of Capsules

Introduction

Polymers Used In Capsules

Gelatin

Stability Issues: Cross-Linking

Hydroxypropylmethylcellulose

Pullulan

Thermal Analysis

Dissolution and Disintegration Testing

Evaluation of Mechanical Properties

Analytical Method Validation

Nutraceuticals

References

Chapter 14 Rheological Aspects of Capsule Shell Excipients and the Manufacture of Encapsulated Formulations

Introduction

Capsule Shell Excipient Solution Rheology and Measurement

Solution Shear Viscosity

Solution Extensional Viscosity

Sol–Gel Transitions

Gel Formation

Gel Point Determination

Gel and Film Characterization

The Rheological Behavior of Capsule Shell Excipients

Capsule Shell Excipient Variability and Its Rheological Assessment

Rheological Aspects of Hard and Soft Shell Capsule Filling

Solids

Semisolids and Liquids

Rheological Behavior of Capsule Shells and of Filled Capsules

Capsule Shells

Filled Capsules

Concluding Remarks

References

Chapter 15 Quality-by-Design (QbD) for Capsule Formulation and Process DevelopmentRegulatory Science Relevance, Scientific Case Studies, and Future Challenges

Regulatory Science Relevance on Pharmaceutical Development

QbD Principles Applied for Capsule Formulation and Process Development

QbD Case Studies for Capsule-Filling Process Control and Product Quality

Effects of Particle Size and Particle Density on ST

Background

Materials and Methods

Segregation Tester

Objective, Study Design, and Testing Results

Effects of Formulation Compositions on Capsule Weight Variation

Background and Methodology of Capsule-Filling Process Characterization

Previous Work on Capsule-Filling Formulation Study

Materials and Manufacturing Process

Capsule Product Weight and Content Analysis

Capsule-Filling Process Characterization and Effect of Formulation Composition on Capsule Fill Weight Variation via a DOE Approach

Effects of Process Variables and Machine Settings on Capsule Weight Variation: A Review of Previous Work and Current Status

Current Challenges and Future Outlook

Acknowledgment

References

Index

 

An aparitie	9 Nov. 2017
Autor	Larry L. Augsburger , Stephen W. Hoag
Dimensiuni	18.42 x 3.18 x 25.4 cm
Editura	CRC Press
Format	Hardcover
ISBN	9781841849768
Limba	Engleza
Nr pag	435