ORAL CAPSULE DOSAGE FORM

Drug Development

HANDBOOK OF PHARMACEUTICAL

GENERIC DEVELOPMENTORALSoft Gelatin
SGCC apsules
IMMEDIATE Release

SGCV OLUME V DRUG DEVELOPMENTPart One

Solid Oral Dosage Forms

HANDBOOK OF PHARMACEUTICAL
GENERIC DEVELOPMENT

24 Volume Pharmaceutical
Generic Development Series
Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

HPGD 24 Vol. SERIES ORAL SG CAPSULES - PART IFirst and Second International Edition - 01/02.
First and Second edition published and distributed in UK, US, EU, RSA, Israel and Japan inNovember 1996-9: by Locum International Publishing House (Houston, Israel, South Africa).
Third International Edition - 03 (First Print).
Second printing published and distributed in UK, US, EU, Israel, Asia, and Japan inFebruary 2000 by Locum International Publishing House (Houston, Israel, South Africa) in
Hard Cover; Soft and Spiral Cover; Electronic Diskette; and e-mail attachment versions. All
print and electronic versions identical in content and format.
Forth International Edition - 04 (First Print) is scheduled for printing in January 2001.
Copyright © 1995 - 2000, Handbook of Pharmaceutical Generic Development.
Text Copyright © 1995 - 2000, Handbook of Pharmaceutical Generic Development.
Illustration copyright © 1995 - 2000, Handbook of Pharmaceutical Generic Development.
Locum International Publishing House PO Box 874, 50 Gilad Street Kochav Yair 44864
Israel. - All right reserved.
ISSN 0793 8656
ISSN 0793 8664 - Electronic Version (Diskette, CD ROM and e-mail attachment version)
Handbook Development 24 volume series
General Generic Development ISSN Series number 0793 7407
General Generic Development ISSN Series number 0793 7792 - Electronic Issue (Disketteand e-mail attachment version are identical in size and content to the printed hard or softcover version. )Duplication: No part of this publication may be reproduced, stored in a retrieval
system or transmitted in any form or by any means, electronic, mechanical,
photocopying, microfilming, recording or otherwise, without the prior written
permission of the copyright owner or subject to the following conditions:
Authorization to photocopy items for internal or personal use or internal or personaluse of specific company personnel, is granted by Locum International Publishing
House, provided that the base fee of $1 per page is paid directly to the Copyright
Clearance Center (CCC) 222 Rosewood Drive, Danvers, MA 01923 USA. For
organizations that have been granted a photocopy license by CCC, a separate
system of payment has been arranged.
For additional information, contact the Publications Department Locum International
Publishing House; PO Box 874, 50 Gilad Street, Kochav Yair, 44864 Israel.
UK Fax: +(44) 207-900 2096
US Fax: +(1) 435-408 1665
Fax: +972-97-494 532
E-mail: info@locum. co. il
http://www.locum.co.il
http://www.locumeuro.com
http://www.locumusa.com
handbooks@l o c u m u s a . com
Current Printing (last digit): 10 9 8 7 6 5 4 3.
sales@l o c u m u s a . com
SERIAL NUMBER - DO NO REMOVE! - REGISTERED WITH

LOCUM INTERNATIONAL PUBLISHERS REGISTRATION SERVICESWARNING: THIS ISSUE A IS MULTIPLE PAGE UV ENCODED EDITION.

Handbook of Pharmaceutical Generic Development

Ö PRINTED IN USA
PRINTED IN ISRAELPRINTED IN IRELAND
PRINTED IN REPUBLIC OF SOUTH AFRICA

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

HANDBOOK OF PHARMACEUTICAL

GENERIC DEVELOPMENTO ral SGC apsules
Solid Dosage FormVOLUME V - Part OneORAL SOFT GELATIN CAPSULES

Jeremy D. Block
D/Pharm.

Third International Edition.
L O C U M

Locum Publishing House - Israel.

P U B L I S H I N G

Locum Pharmaceutical Publishers - USA

Handbook of Pharmaceutical Generic Development

H O U S E

Locum International Publishers - Cape Town

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

Handbook of Pharmaceutical
Generic Development Series
45 Volume Series - Compiled by:

J. D . BLOCK
BSc. MPS. D/PHARM.
Research Director Generic & Innovative Drug Development Division, Locum International Group.
Science Editor - International Journal of Generic Drugs & International Journal of Drug Development
School of Pharmacy University of the Witwatersrand and Witwatersrand Technikon
Johannesburg RSA.

Edited:IAGIM Scientific Committee
Review Process:
Generic & Innovative Drug Development Division
Locum International Research Center

Handbook of Pharmaceutical Generic Development

Vol. 1 - Tablets

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 2 - Capsules

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 3 - Semisolids

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 4 - Liquids

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 5 - SG Capsules

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 6 - e-SOPs / SOPs.

Part I (Development Stability) & Part II (Analytical, Micro, PAI)

Handbook of Pharmaceutical Generic Development

Vol. 7 - Suspensions

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 8 - Eye & Nose

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 9 - Aerosols MDIPart I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 10 -Tablets CR/MRPart I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 11 -Capsules ER

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development
Handbook of Pharmaceutical Generic Development

Vol. 12 - Tablets Oral DR
Vol. 13 - Analytical

Part I (Method Validation) & Part II (Analytical Methods 1994-2003)(Top 50 Generic Assay Methods)

Handbook of Pharmaceutical Innovative Development
Handbook of Pharmaceutical Innovative Development
Handbook of Pharmaceutical Innovative Development
Handbook of Pharmaceutical Drug Development (1-5)

Vol. 14 - Tablets Oral
Vol. 15 - Capsules Oral
Vol. 16 - Suspensions Oral
Vol. 17 - MF and MMI(Master Formula & Manufacturing Instructions Parts 1 - 5)

Handbook of Pharmaceutical Drug Development (6-10)

Vol. 18 - MF and MMI(Master Formula & Manufacturing Instructions Parts 6 - 10)

Handbook of Pharmaceutical Innovative Development

Vol. 19 - SOPs/PAI-Checklist

Part I, Part II & Part III.(Development, Manufacturing & Engineering)

Handbook of Pharmaceutical Drug Development

Vol. 20 - Sterile Injections

Available either on Online, CD ROM or via electronic mail attachment.
Additional Drug Specific Volumes in Preparation. An on-going electronic and print series
Available either as Hard Bound, Soft Bound or Soft Spiral Cover (for Updating).

For Drug Specific Handbooks refer to the 120+ Drug Development Series titled
READY-TO-GO™ DRUG DEVELOPMENT SERIES

http://www.locumusa.com/2go & http://www.iagim.org
Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORMDrug Development

Handbook of
Pharmaceutical

GenericDevelopment

Oral
SOFT GELATINCAPSULESPartOne

DRUG Development
Locum International Publishers

Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

Electronic < Handbook Series of
Pharmaceutical Generic Development
ISSN 0793 8667 - Electronic Version
Handbook Development 45 Volume Series
ISSN Series Number 0793 761X - Electronic Version

Handbook of Pharmaceutical Generic Development

Vol. 1 - Tablets

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 2 - Capsules

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 3 - Semisolids

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 4 - Liquids

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 5 - SG Capsules

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 6 - e-SOPs / SOPs.

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 7 - SuspensionsPart I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 8 - Eye & Nose

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 9 - Aerosols MDIPart I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 10 -Tablets CR/MRPart I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development

Vol. 11 -Capsules ER

Part I (Development) & Part II (Model ANDA or EU Dossier)Handbook of Pharmaceutical Generic Development
Handbook of Pharmaceutical Generic Development

Vol. 12 - Tablets Oral DR
Vol. 13 - Analytical

Part I (Method Validation) & Part II (Analytical Methods 1994-2003)(Top 50 Generic Assay Methods)

Handbook of Pharmaceutical Innovative Development
Handbook of Pharmaceutical Innovative Development

Vol. 14 - Tablets Oral
Vol. 15 - Capsules Oral

Handbook of Pharmaceutical Innovative Development
Handbook of Pharmaceutical Drug Development (1-5)

Vol. 16 - Suspensions Oral
Vol. 17 - MF and MMI(Master Formula & Manufacturing Instructions Parts 1 - 5)

Handbook of Pharmaceutical Drug Development (6-10)

Vol. 18 - MF and MMI(Master Formula & Manufacturing Instructions Parts 6 - 10)

Handbook of Pharmaceutical Innovative Development

Vol. 19 - SOPs/PAI-Checklist

Part I, Part II & Part III.(Development, Manufacturing & Engineering)

Handbook of Pharmaceutical Drug Development

Vol. 20 - Sterile Injections

Available either on Online, CD ROM or via electronic mail attachment.
Additional Drug Specific Volumes in Preparation. An on-going electronic and print series
Available either as Hard Bound, Soft Bound or Soft Spiral Cover (for Updating).

For Drug Specific Handbooks refer to the 120+ Drug Development Series titled
READY-TO-GO™ DRUG DEVELOPMENT SERIES

http://www.locumusa.com/2go

Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

Acknowledgments
I.A.G.I.M. (R&D) Foundation.

I.A.G.I.M. Members (1994 - 2000).
Contributions - Generic & Research Firms
Associate Universities, Technicons and Consultants.
Handbook Series Coordinating Committee.
International Journal of Drug Development.
Journal of Pharmaceutical Development.
International Journal of Generic Drugs.
I.A.G.I.M. Drug Development Archives
Locum International Archives.
FDA/OGD/CDER Maryland
Guides and Guidelines
Library of Congress.
AIC Conferences.
Editorial Board.
Pharm. Eur.
USP/NF.
USPC.
BP.
°

To Doribelle
for her years of support and help
to Sean for his expert knowledge on computerization
to David and Ari for running the project's computersand lastly to Pat for his inestimablecontribution.

Third International Edition.
2000

L O C U M

P U B L I S H I N G

H O U S E

Í°Î
ÏÐÍ°Î

Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series

ORAL CAPSULE DOSAGE FORM

Drug Development

INTRODUCTION
Handbook of Generic Development - Oral Soft Gelatin Capsules
This handbook is the third international edition of the ongoing 24 volume series
under the cumulative title of Handbook of Generic Drug Development. It is a handson, technical presentation that portrays the current drug requirement steps
necessary at the time of going to print, of the Abbreviated New Drug Application fororal dosage form, namely soft gelatin capsules.
It is written in conjunction with Part Two of the Handbook which models thedevelopment requirements of a representative ANDA and as an example of the drug
development process required for SGC oral dosage forms. The Handbook isavailable in electronic format (CD ROM) and e-format (on-line). The Handbook is
up-dated to current regulatory requirements once to twice annually. Complete
updates are available without charge to Association Members of the Drug
Development Association - IAGIM.

This handbook provides a proven pathway to solid oral dosage form development.
Modern commercial formulations highlight the common soft gelatin capsuledevelopment routes namely the oil and paste filled formulations. Low active dosage(0.25 mcg) and high potency (500 mg) examples are specially chosen todemonstrate and highlight the formulation steps and process stages absolutely
necessary as a prerequisite to developing a stable, elegant and rugged formula.

This third edition of the Handbook includes additional data on analytical methodvalidation has been redesigned to meet the January 2000 Guidance for Industry Organization of an Abbreviated New Drug Application as well as all FDA guideline
and requirements of the Center of Drug Evaluation and Research (CDER) up tocurrent edition date.
Editor-in-Chief.

ÓšÎThird International Edition
p20±00p© COPYRIGHT 1995-00

Ï›Ð

ISSN 0793 8656

An on-going series
45 Volume Series.

Additional Volumes in Preparation
General Drug Development Series ISSN 0973 7601
Electronic Drug Development Series ISSN 0973 761X

Handbook of Pharmaceutical Generic Development

24 volume Drug Development Series