Handbook of Pharmaceutical Manufacturing Formulations, Third Edition-Volume One, Compressed Solid Products

593 Pages·2019·9.19 MB·\593

by  Sarfaraz K. Niazi (Author)

Handbook of Pharmaceutical
Manufacturing Formulations
Volume One, Compressed Solid Products

Handbook of Pharmaceutical
Manufacturing Formulations,
Third Edition
Volume One, Compressed Solid Products
Sarfaraz K. Niazi
CRC Press
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To the memory of Sidney Riegelman
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Contents
Preface to the Series—Third Edition ......................................................................................................................................xxvii
Preface to the Series—Second Edition ....................................................................................................................................xxix
Preface to the Series—First Edition .....................................................................................................................................xxxiii
Preface to the Volume—First Edition.....................................................................................................................................xxxv
Author ...................................................................................................................................................................................xxxvii
PART I Regulatory and Manufacturing Considerations
Chapter 1 Bioequivalence Testing: Rationale and Principles ..................................................................................................3
I. Background ...................................................................................................................................................3
II. Evidence to Measure Bioequivalence ...........................................................................................................4
III. Pivotal Parameters for Blood-Level Bioequivalence ....................................................................................6
A. Area Under the Curve Estimates ...........................................................................................................6
IV. Rate of Absorption .......................................................................................................................................7
V. Determination of Product Bioequivalence ...................................................................................................7
VI. Errors in Bioequivalence Studies .................................................................................................................7
VII. Absorption Profiling .....................................................................................................................................8
VIII. Pharmacokinetic Measures of Systemic Exposure ......................................................................................9
A. Early Exposure .....................................................................................................................................9
B. Peak Exposure .......................................................................................................................................9
C. Total Exposure ......................................................................................................................................9
IX. Statistical Analysis .......................................................................................................................................9
X. Untransformed Data .....................................................................................................................................9
XI. Logarithmically Transformed Data ............................................................................................................10
Bibliography ..........................................................................................................................................................11
Appendix: Bioavailability and Bioequivalence Studies Submitted in NDAs
or INDs—General Considerations ......................................................................................................13
I. Introduction ..............................................................................................................................13
II. Background ..............................................................................................................................14
III. Methods to Document BA and BE ..........................................................................................15
IV. Documenting BA and BE for Various Dosage Forms ..............................................................18
V. Additional Information on in Vitro Approaches .......................................................................20
VI. Special Topics ..........................................................................................................................22
Appendix A: General Study Design and Data Handling ...................................................................24
Chapter 2 Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage
Forms Based on a Biopharmaceutics Classification System: Guidance for Industry ...........................................27
I. Introduction ................................................................................................................................................27
II. The Biopharmaceutics Classification System.............................................................................................27
A. Solubility ............................................................................................................................................28
B. Permeability ........................................................................................................................................28
C. Dissolution ..........................................................................................................................................28
III. Recommended Methodology for Classifying a Drug Substance and for Determining the
Dissolution Characteristics of a Drug Product ...........................................................................................28
A. Determining Drug Substance Solubility Class ...................................................................................28
B. Determining Drug Substance Permeability Class ...............................................................................29
C. Determining Drug Product Dissolution Characteristics and Dissolution Profile Similarity ..............31
IV. Biowaivers Based on Bcs ............................................................................................................................31
V. Additional Considerations for Requesting A Biowaiver ............................................................................32
vii
viii Contents
A. Excipients ...........................................................................................................................................32
B. Prodrugs ..............................................................................................................................................32
C. Fixed Dose Combinations Containing BCS Class 1, or Class 3, or a
Combination of Class 1 and 3 Drugs ............................................................................................32
D. Exceptions ..........................................................................................................................................33
VI. Regulatory Applications of the Bcs–Based Biowaivers .............................................................................33
A. INDs/NDAs ........................................................................................................................................33
B. ANDAs ................................................................................................................................................33
C. Supplemental NDAs/ANDAs (Postapproval Changes) ......................................................................33
VII. Data to Support a Biowaiver Request .........................................................................................................33
A. Data Supporting High Solubility ........................................................................................................33
B. Data Supporting High Permeability ....................................................................................................34
C. Data Supporting Rapid, Very Rapid, and Similar Dissolution ............................................................34
D. Additional Information .......................................................................................................................34
Attachment A .........................................................................................................................................................34
Chapter 3 Product-Specific Guidance from FDA on the Development of Compressed Dosage Forms................................37
Chapter 4 Guidance on Formulating Compressed Solids ......................................................................................................41
Background ...........................................................................................................................................................41
Tablet Types ...........................................................................................................................................................41
Formulation Factors...............................................................................................................................................44
I. Active Pharmaceutical Ingredient ............................................................................................................44
II. Bio versus Production Batches .................................................................................................................44
III. Cleaning Validation ..................................................................................................................................44
IV. Coatings ....................................................................................................................................................44
V. Compliance with Regulatory Requirements ............................................................................................45
VI. Compression Process Control ...................................................................................................................45
VII. Content Uniformity ..................................................................................................................................45
VIII. Cross-Contamination ................................................................................................................................45
IX. Desegregation of Powders ........................................................................................................................45
X. Disintegration Test ....................................................................................................................................45
A. Uncoated Tablets ...............................................................................................................................46
B. Plain Coated Tablets..........................................................................................................................46
C. Delayed-Release (Enteric-Coated) Tablets .......................................................................................46
D. Buccal Tablets ...................................................................................................................................46
E. Sublingual Tablets .............................................................................................................................46
XI. Dissolution ................................................................................................................................................46
XII. Disintegration and Dissolution .................................................................................................................46
XIII. Drug Substance Characterization .............................................................................................................46
XIV. Drying Process .........................................................................................................................................47
XV. Dyes in Formulations ...............................................................................................................................47
XVI. Equipment .................................................................................................................................................47
A. Blenders ............................................................................................................................................47
B. Dryers ................................................................................................................................................48
C. Tablet Compression Equipment ........................................................................................................48
D. Coating Equipment ...........................................................................................................................49
XVII. Excipients .................................................................................................................................................49
A. Coating Agent ...................................................................................................................................49
B. Glidant ..............................................................................................................................................49
C. Tablet Binder .....................................................................................................................................50
D. Diluent ..............................................................................................................................................50
E. Disintegrant .......................................................................................................................................50
F. Lubricant ...........................................................................................................................................50
XVIII. Direct Compression ..................................................................................................................................51
Contents ix
XIX. Fill Weights ........................................................................................................................................51
XX. Final Packaging ..................................................................................................................................51
XXI. Final Testing .......................................................................................................................................51
XXII. Fines ...................................................................................................................................................51
XXIII. Formula Excesses ...............................................................................................................................51
XXIV. Geometric Dilution ............................................................................................................................52
XXV. Granulation/Mix Analysis .................................................................................................................52
XXVI. Ingredient Warning ............................................................................................................................52
XXVII. In-Process Testing ..............................................................................................................................52
XXVIII. Loss on Drying ...................................................................................................................................53
XXIX. Manufacturing Yields ........................................................................................................................53
XXX. Master Formula ..................................................................................................................................53
XXXI. Multiple-Item Entries .........................................................................................................................53
XXXII. Multiple Strengths of Formulations ...................................................................................................53
XXXIII. Novel Drug Delivery Systems ............................................................................................................54
XXXIV. Particle Coating ..................................................................................................................................54
XXXV. Preservatives in Compressed Solid Dosage Formulations .................................................................54
XXXVI. Punch Size and Shape ........................................................................................................................54
XXXVII. Reworking Culls ................................................................................................................................55
XXXVIII. Scale-Up .............................................................................................................................................55
XXXIX. Segregation .........................................................................................................................................55
XL. Sifting Ingredients And Granules ......................................................................................................55
XLI. Specifications .....................................................................................................................................55
XLII. Stability Testing .................................................................................................................................55
XLIII. Storage of In-Process Material ..........................................................................................................56
XLIV. Tablet Friability ..................................................................................................................................56
XLV. Tablet Manufacturing .........................................................................................................................56
XLVI. Tablets ................................................................................................................................................56
XLVII. Water-Purified Usp .............................................................................................................................57
XLVIII. Weight Variation and Content Uniformity .........................................................................................57
XLIX. Wet Granulation versus Dry Granulation or Direct Compression .....................................................57
L. Multivariate Methods in Tablet Formulation .....................................................................................58
LI. Physical Properties .............................................................................................................................59
LII. Particle Size Studies ...........................................................................................................................59
A. Particle Size Distribution ...........................................................................................................60
LIII. Surface Area ......................................................................................................................................61
LIV. Porosity...............................................................................................................................................61
LV. True Density .......................................................................................................................................62
LVI. Flow and Compaction of Powders .....................................................................................................62
LVII. Color ...................................................................................................................................................63
LVIII. Electrostaticity ...................................................................................................................................63
LIX. Caking ................................................................................................................................................64
LX. Polymorphism ....................................................................................................................................64
LXI. Stability Studies to Select Optimal Drug and Excipient Combinations ............................................65
Appendix A ................................................................................................................................................................................67
Appendix B ................................................................................................................................................................................87
Appendix C ..............................................................................................................................................................................177
PART II Manufacturing Formulations
Compressed Solids Formulations ..........................................................................................................................................213
Acetaminophen and Caffeine Tablets ..................................................................................................................213
Acetaminophen and Caffeine Tablets ..................................................................................................................213
Acetaminophen and Codeine Tablets (Tylenol) ..................................................................................................213