Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Second Edition

by Banga; Ajay K.

• ISBN13: 9780849316302
• ISBN10: 0849316308
• Edition: 2nd
• Format: Hardcover
• Copyright: 2005-09-14
• Publisher: CRC Press

Summary

Upon publication of the first edition of Therapeutic Peptides and Proteins ten years ago there were only 19 biotechology medicines on the market. Currently there are more than 100, with at least 400 more in various stages of development. That alone would be grounds for a new edition. Add to that the fact that it is still difficult to find up-to-date, relevant information on protein formulation and/or delivery systems and the need for a new edition is self-evident. This second edition continues the tradition of providing a ready-to-use reference of accurate information, tables, and illustrations.The book begins with the basics of the origin of recombinant proteins, explores structural and analytical aspects, and moves on to discuss the stability of proteins and peptides. Against this background, the author addresses preformulation and formulation considerations and provides detailed information on important topics such as lyophilization. He goes on to discuss various delivery systems, including controlled release delivery systems and products currently on the market. The book also contains newly added regulatory information and thoroughly investigates therapeutic drugs made from proteins as well as protein-based vaccines. A new chapter on recombinant protein subunit vaccines and their delivery systems has been added.The work of a single author, the book provides complex information in a simple, elegant, and cohesive style. The author minimizes overlap between coverage and includes extensive cross-referencing that links related topics. Completely revised and updated, packed with cutting-edge information, the second edition once again fills the need for a reference that pulls all the relevant information together into one resource.

Table of Contents

Pharmaceutical Biotechnology: The Arrival of Recombinant Proteins	1	(32)
What is biotechnology?	1	(10)
Recombinant DNA technology	2	(2)
Monoclonal antibodies	4	(3)
Expanding scope of biotechnology	7	(1)
Antisense agents and RNAi	8	(1)
Transgenic therapeutics	9	(1)
Gene therapy	9	(1)
Human Genome Project	10	(1)
The biotechnology industry	11	(6)
Biotechnology products on the market	11	(1)
Human insulins and analogues	12	(2)
Growth hormone	14	(1)
Interferons	14	(1)
Dornase alfa	15	(1)
Antimicrobial peptides	16	(1)
Tissue plasminogen activator	16	(1)
Fusion proteins	16	(1)
Miscellaneous	17	(1)
Regulatory aspects of biotechnology-derived drugs	17	(5)
Preclinical and clinical studies	19	(1)
Pharmacoeconomics and the regulatory process	20	(1)
Characterization and purity of biotechnology-derived proteins	21	(1)
Patents	22	(1)
Immunogenicity of proteins	22	(2)
Structure-based drug design	24	(1)
Conclusions	25	(8)
Structure and Analysis of Therapeutic Peptides and Proteins	33	(34)
Amino acids: building blocks of proteins	33	(1)
Structure of peptides and proteins	34	(4)
Primary structure	35	(1)
Secondary structure	35	(1)
Tertiary structure and protein folding	36	(2)
Quaternary structure	38	(1)
Protein conformation and other structural features	38	(3)
Analytical methods	41	(15)
Electrophoresis	41	(2)
Spectroscopy	43	(1)
Ultraviolet spectroscopy	43	(1)
Fluorescence spectroscopy	43	(1)
Circular dichroism spectroscopy	44	(1)
Infrared spectroscopy	45	(1)
Light scattering	46	(1)
Colorimetric assay	47	(1)
Chromatography	48	(1)
Reverse-phase chromatography	48	(1)
Size exclusion chromatography	49	(1)
Other chromatographic techniques	50	(1)
Thermal analysis	50	(1)
Immunoassays and bioassays	51	(2)
Other quality control procedures	53	(1)
Peptide mapping	54	(1)
Analytical ultracentrifugation	55	(1)
Analysis of glycoproteins	55	(1)
Conclusions	56	(11)
Stability of Therapeutic Peptides and Proteins	67	(24)
Introduction	67	(1)
Physical instability	68	(7)
Denaturation	68	(1)
Aggregation	69	(1)
Mechanism of aggregation	70	(2)
Aggregation behavior in liquid and solid states	72	(1)
Adsorption	73	(2)
Chemical instability	75	(7)
Oxidation	75	(2)
Hydrolysis	77	(1)
Deamidation	78	(1)
β-Elimination and disulfide exchange	79	(1)
Racemization	80	(1)
Thermal stability	80	(1)
Multiple pathways of chemical instability	80	(2)
Well-characterized products and comparability protocols	82	(1)
Conclusions	83	(8)
Preformulation and Formulation of Therapeutic Peptides and Proteins	91	(48)
Introduction	91	(7)
Preformulation studies	98	(1)
Formulation development	99	(5)
Buffer system	100	(1)
pH of the vehicle	101	(1)
Protein solubility	101	(2)
Selection of solvent system	103	(1)
Preservation of a formulation	103	(1)
Choice of container	104	(1)
Pharmaceutical excipients in formulations	104	(12)
Albumin	106	(1)
Amino acids	107	(1)
Carbohydrates	108	(1)
Chelating and reducing agents	108	(1)
Cyclodextrins	109	(1)
Polyhydric alcohols	110	(1)
Polyethylene glycol	111	(1)
Salts	111	(1)
Surfactants	112	(2)
Miscellaneous	114	(1)
Selection of excipient	114	(2)
Aggregation in protein formulations	116	(5)
Aggregation behavior of insulin	116	(3)
Aggregation behavior of human growth hormone	119	(1)
Aggregation behavior of α1-antitrypsin	119	(1)
Aggregation behavior of human interferon	120	(1)
Aggregation of monoclonal antibodies	120	(1)
Aggregation behavior of some other proteins	121	(1)
Novel formulation approaches	121	(4)
Liposomes	122	(1)
Reverse micelles	123	(1)
Emulsions	123	(1)
Genetic engineering or chemical modification	124	(1)
Accelerated stability testing	125	(2)
Statistical design for formulation development	127	(1)
Conclusions	128	(11)
Lyophilization, Pharmaceutical Processing, and Handling of Therapeutic Peptides and Proteins	139	(38)
Introduction	139	(1)
Protein destabilization induced by pharmaceutical processing	140	(3)
Adsorption induced by pharmaceutical processing	140	(1)
Aggregation induced by pharmaceutical processing	141	(1)
Shaking	141	(1)
Hydrophobic surfaces	142	(1)
Heating	142	(1)
Shear-induced aggregation	142	(1)
Miscellaneous factors	143	(1)
Lyophilization as a pharmaceutical process	143	(11)
Process details	144	(1)
Maximum allowable product temperature	145	(1)
Measurement of lyophilization-induced thermal changes	146	(1)
Protein denaturation during lyophilization	147	(1)
Freeze-thaw stability	147	(2)
Formulation components for lyophilization	149	(1)
Bulking agents	149	(1)
Tonicity modifiers	149	(1)
Cryoprotectants and lyoprotectants	150	(1)
The lyophilization cycle	151	(3)
Alternative pharmaceutical processes	154	(5)
Spray-drying	155	(1)
Use of nonaqueous solvents	156	(1)
Compaction and tablets	156	(1)
Aerosolization	157	(2)
Handling of therapeutic peptides and proteins	159	(8)
Sterilization	159	(1)
Sanitizing agents and protein stability	159	(1)
Preparation of a typical batch	160	(1)
Storage in solid state	161	(2)
Handling of recombinant proteins in a hospital setting	163	(1)
Reconstitution	163	(2)
Incompatibilities	165	(1)
Adsorption	166	(1)
Other considerations	167	(1)
Conclusions	167	(10)
Parenteral Controlled Delivery and Pharmacokinetics of Therapeutic Peptides and Proteins	177	(52)
Introduction	177	(2)
Pharmacokinetics of peptide and protein drugs	179	(8)
Pharmacokinetic parameters	180	(1)
Volume of distribution	180	(1)
Clearance	181	(1)
Half-life	182	(1)
Other pharmacokinetic/pharmacodynamics considerations	182	(1)
Pharmacodynamics	183	(1)
Antibody induction	183	(1)
Interspecies scaling	183	(1)
Chemical modification to control protein disposition	184	(2)
Transport of peptides across the blood-brain barrier	186	(1)
Polymers used for controlled delivery of peptides and proteins	187	(4)
Nondegradable polymers	188	(1)
Biodegradable polymers	189	(2)
Parenteral controlled release systems	191	(14)
Microspheres	191	(1)
Release of drugs from microspheres	192	(1)
Preparation of microspheres	193	(2)
Microsphere formulations of luteinizing hormone-releasing hormone and analogues	195	(2)
Implants	197	(2)
Liposomes	199	(1)
Nanoparticles	200	(1)
Vaccines	201	(1)
Pulsatile drug delivery systems	201	(1)
Externally regulated or open-loop systems	202	(1)
Pumps	202	(1)
Self-regulated or closed-loop systems	203	(2)
Innovations in parenteral administration of proteins	205	(3)
Pegylated proteins	205	(1)
Protein crystals	206	(1)
Prefilled syringes and needle-free injections	207	(1)
Examples of protein pharmacokinetics	208	(4)
Interferon	208	(1)
Interleukins	208	(1)
Insulin	209	(2)
Epoetin	211	(1)
Miscellaneous	211	(1)
Conclusions	212	(17)
Oral Delivery of Peptide and Protein Drugs	229	(30)
Introduction	229	(2)
Barriers to protein absorption and pathways of penetration	231	(4)
Extracellular barriers	231	(1)
Cellular barriers	232	(3)
Approaches to improve oral delivery	235	(10)
Site-specific drug delivery	235	(2)
Chemical modification	237	(2)
Bioadhesive drug delivery systems	239	(1)
Penetration enhancers	240	(2)
Protease inhibitors	242	(1)
Carrier systems	243	(2)
Other formulation approaches	245	(1)
Methods to study oral absorption	245	(4)
Intestinal segments	245	(1)
In vivo studies	246	(1)
Diffusion cells	246	(1)
Cell cultures	246	(2)
Brush border membrane vesicles	248	(1)
Oral immunization	249	(1)
Conclusions	250	(9)
Transdermal and Topical Delivery of Therapeutic Peptides and Proteins	259	(32)
Introduction	259	(1)
Skin Structure	260	(3)
Pathways of transdermal delivery	262	(1)
Enzymatic barrier of skin	263	(1)
Approaches to enhance transdermal peptide delivery	263	(6)
Skin microporation	263	(2)
Phonophoresis	265	(1)
Prodrug approach	266	(1)
Permeation enhancers	266	(2)
Protease inhibitors	268	(1)
Other technologies	269	(1)
Iontophoresis	269	(9)
Factors affecting iontophoretic delivery	271	(1)
Molecular weight	271	(1)
Drug charge	272	(1)
Current density	272	(1)
Electrode material	273	(1)
Examples of iontophoretic delivery of therapeutic peptides	274	(1)
Amino acids and small peptides	274	(1)
Oligopeptides	275	(1)
Polypeptides	275	(1)
Insulin	276	(1)
Commercialization of iontophoretic delivery	277	(1)
Topical delivery of therapeutic peptides and proteins	278	(3)
Growth factors	279	(1)
Liposomes	279	(2)
Iontophoresis and phonophoresis	281	(1)
Conclusions	281	(10)
Pulmonary and Other Mucosal Delivery of Therapeutic Peptides and Proteins	291	(36)
Introduction	291	(2)
Pulmonary delivery	293	(8)
Drug deposition in the respiratory tract	294	(1)
Drug absorption from the respiratory tract	295	(1)
Drug delivery devices	296	(1)
Formulation of peptides/proteins for pulmonary delivery	297	(3)
Commercialization and regulatory considerations	300	(1)
Nasal delivery	301	(6)
Approaches to overcome barriers to nasal absorption	302	(1)
Penetration enhancers	302	(5)
Rectal delivery	307	(1)
Buccal delivery	308	(2)
Ocular delivery	310	(2)
Mechanism of ocular penetration	310	(1)
Ocular route for systemic delivery	311	(1)
Insulin	311	(1)
Enkephalins	311	(1)
Ocular route for topical delivery	312	(1)
Comparative evaluation of mucosal routes	312	(1)
Conclusions	313	(14)
Recombinant Protein Subunit Vaccines and Delivery Methods	327	(24)
Introduction	327	(5)
Vaccine adjuvants	330	(1)
Subunit vaccines	331	(1)
DNA vaccines	331	(1)
Heat shock proteins	332	(1)
Immunology relevant to vaccines	332	(3)
Immune responses to vaccines	334	(1)
Routes of administration	335	(6)
Intranasal immunization	337	(1)
Transcutaneous immunization	338	(1)
Oral immunization	339	(1)
Other mucosal routes	340	(1)
Delivery approaches for administration of vaccines	341	(2)
Liposomes	342	(1)
Particle-mediated immunization	342	(1)
Microspheres	343	(1)
Case example: Hepatitis B	343	(1)
Future outlook and regulatory status	344	(1)
Conclusions	344	(7)
Index	351