~ Remingtorfs
`Pharmaceutical
`Sciences
`
`information about pharmaceutical and medicinal
`Aitreatise on the theory and practice of pharmaceutical sciences, with essential
`,
`.
`I
`_
`_
`.
`agents; also a guide to the professional responsibilities and services at the pharmacist asa member of the health team .
`.
`.
`. A text-
`book and reference work for pharmacists, physicians, and other, medical scientists
`
`'EDITORIAL BOARD MEMBERS
`
`Arthur Osol, Chairman
`
`Alfonso R. Gennaro
`Harolol S. Hutchison
`Ewart A. Swinyard
`
`Melvin R. Gibson
`I Walter Kowalick
`Linwood F. Tice
`
`_
`
`Stewart C. Harvey
`Alfred N. Martin
`Clarence T. Van Meter
`
`SECTION EDITORS}
`
`John T. Anderson
`.
`llfonso‘, R. Gennaro
`Robert -E. King
`
`Grafton D. Chase
`Cecil L. Bendush
`3 Stewart C. Harvey
`Melvin R. Gibson
`C. Boyd Granberg
`Alfred N. Martin
`'
`Ewart A. Swinyarol
`
`MANAGING EDITOR
`
`John E. Hoover
`
`With the cooperation of more than 300 editors, associate editors, and contributors
`Over 1,000 Illustrations
`
`FIFTEENTH EDITEON
`
`1975
`
`Published in the 155th Year
`
`a
`
`of the
`
`Philadelphia College of Pharmacy and Science
`
`MACK PUBLISHING COMPANY
`
`Easton, Pennsylvania 18042
`
`3.95388
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC
`
`RBP_TEVA05022439
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC
`
`

`
`Entered according to Act of Congress, in the year 1885 by Joseph P. Remington,
`in the Office of the Librarian of Congress, at Washington, D. C.
`'
`
`Copyright 18‘89, 1894, 1905, 1907, 1917, by Joseph P. Remington
`Copyright 1926, 1936, by Joseph P. Remington Estate
`Copyright 1948, 1951, by The Philadelphia College of Pharmacy and Science
`Copyright © 1956, 1960, 1965, 1970, 1975, by The Philadelphia College of Pharinacy
`and Science
`.
`‘
`
`All Rights Reserved
`
`Library of Congress Catalog Card No. 60433334
`
`The use of portions of the text of USP XIX and NF XIV is by permission of the
`USP. Convention. Neither the Convention nor the American Pharmaceutical
`' Association, original publisher of the N.F., is responsible for any inaccuracy of
`quotation or for any false or misleading implication that may arise from
`separation of excerpts from the original context or by obsolescence resulting
`from publication ofa supplement.
`Notice
`.
`This text is not intended to represent, nor shall it be interpreted to be, the equivalent
`of 01‘ a substitute for the official United States Pharmacopeia (USP) and/or
`the National Formulary (NF). In the event of any difference or discrepancy
`between the current official USP or NF standards of strength, quality, purity,
`packaging and labeling for drugs and representations of them herein, the
`context and effect of the official compendia shall prevail.
`
`Authority to use selected portions of the text of the second edition of AMA Drug
`Evaluations has been granted by the American Medical Association. The
`American Medical Association is not responsible for any inaccuracies of the
`text thus used.
`
`Printed in the United States ofAmerica by the Mach Printing Company, Easton, Pennsylvania
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC
`
`RBP_TEVA05022440
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC
`
`

`
`. _________.___...._____..._...._....._.___._...._.._......................._..........._.__..._...._.......__.__..._..________
`
`Table
`
`of Contents
`
`Orientation
`
`.
`
`.
`
`PART 1
`General Notices .
`Scope........
`Evolution of Pharmacy .
`Ethics.
`.
`.
`.
`'.
`Pharmacists in Practice.
`_ Pharmacists in industry .
`Pharmacists in Government
`Literature .
`Research .
`
`oo\io>'cn'.z>wro—x
`
`PART 2
`
`Phannaceufics
`
`9
`10
`11
`12
`18
`
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`
`.
`
`Metrology and Calculation .
`Statistics.
`.
`.
`.
`.
`-.
`.
`Computer Science .
`Calculus........‘.......r..V..
`Atomic and Molecular Structure and the States of
`Matter....‘
`..
`.
`Coijnplexation.
`g
`Quantum Chemistry .
`.
`.
`.
`Thermodynamics.
`I
`.
`.
`Solutions and Phase Equilibria.'
`Ionic Solutions and Electrolytic Equilibria .
`Reaction Kinetics.
`.
`.
`.
`.
`.
`.
`.
`.
`1/lntertacial Phenomena .
`"Colloidal Dispersions .
`‘Coarse Dispersions .
`Particle Phenomena .
`Rheology.
`
`.
`
`.
`
`Phannaceuficalchenfishy
`
`lnorganic Pharijnaceutical Chemistry ..
`Organic Pharmaceutical Chemistry .
`. ..
`.
`.
`.
`.
`NaturalProducts.
`.
`.
`.
`.
`.
`.
`.
`Drug Nomenclature—United States Adopted Names .
`Structure—Activity Relationship and Drug Design .
`
`.
`
`PART 3'
`25
`26
`27
`28
`29
`
`PART 4
`
`30
`31 = Fundamentals of Radioisotopes .
`MedmaiApmmaflonsotRamobompes :
`
`Radioisotopes in Pharmacy and Medicine‘
`473
`
`Testingand Analysis
`PART 5
`1 32
`Official Requirements and Tests .
`33
`Analysis of Medicinals.
`1'
`‘
`34
`Bkuogéalresnng ..
`35
`.
`Clinical Analysis.
`.
`36'
`.
`.
`.
`.
`Chromatography.
`37
`Instrumental Methods of Analysis .
`
`.
`
`.
`
`PART 6
`
`38
`39
`40
`41
`42
`43
`44
`45
`46
`47
`48
`49
`50
`
`Pharmaceutical and Medicinal Agents
`Drug Absorption, Action, and Disposition.
`.
`Topical Drugs 1.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`.
`..
`.
`.
`f Gastrointestinal Drugs‘.
`.
`.
`._
`.
`Blood, Fluids, Electrolytes, and Hematologic Drugs
`Cardiovascular Drugs ,
`.
`.
`.
`.
`.
`Respiratory Drugs .
`.
`.
`.
`.
`.
`.
`.
`._
`Sympathomimetic Drugs .
`Oholinomimetlc (Parasympathomimetic) Drugs .
`Adrenergic Blocking Drags .
`.
`.
`.
`Antimuscarinic Drugs .
`.
`.
`Skeletal Muscle Relaxants
`.
`Diuretic Drugs .
`Uterine Drugs .
`
`.
`
`.
`
`.
`
`.
`
`.
`
`.
`
`371
`"394
`416
`446
`454
`
`492
`
`669
`712
`731
`754
`780
`798
`807
`825
`833
`839
`851
`861
`874
`
`.
`
`.
`51 Hormones... ... .
`52 Vitamins and Other Nutrients.
`53 Enzymes.
`.
`.
`.
`.
`54 General Anesthetic
`.
`.
`55 Local Anesthetics.
`56
`sedatives and Hypnctics .
`.
`.
`57
`--Antiepileptics
`.
`.
`.
`.
`58
`Psychopharmacologic Agents .
`59 Analgesics and Antipyretics .
`'
`60 Histamine and Antihistamines.
`61
`.
`l
`Central Nervous System Stimulants. .
`62
`Antineoplastic and lmmunosuppressive Drugs.
`63
`Antimicrobial Drugs .
`64
`Parasiticides .
`.
`Pesticides.
`.
`,65
`.66
`.
`Diagnostic Drugs.
`67
`.
`.
`Pharmaceutical Necessities .
`68
`.
`.
`Adverse Ettects of Drugs .
`.
`69
`Pharmacological Aspects of Drug Abuse
`70'
`introduction of New Drugs .
`
`.
`
`.
`
`.
`
`PART 7
`
`Biological Products
`
`Principles of immunology.
`71
`immunizing Agents .
`72
`73 Diagnostic Biologicals .
`74 Allergenic Extracts .
`
`1315
`1324
`1341
`1344
`
`PART 8
`
`PhannaceuficalPreparafionsand’Thefl
`hnanutacture
`
`sting .
`
`I
`
`.
`
`.
`
`.
`
`.
`
`1461509
`1523
`1554
`1 1576
`1608
`1618
`1644
`
`O|'fTlS .
`
`-.
`
`1355
`.
`.
`.
`.
`.
`.
`.
`Formulation.
`75
`1353
`Bioavailat/nility and Bioequivalency Te
`76
`1375
`77 ,Separa"'
`.
`.
`.
`.
`.
`.
`.
`.
`'1389
`1405
`78<;$tefiHzafiog;)-m\.
`.
`L
`.‘.
`79
`Isetonic.-soltftions‘.
`1413
`80
`Plastic Packaging-Materials.
`.__2J&J91429
`81 s1wi ma1m5_ug U.-'c..',.L.,;_'_; .
`'
`82 Control.
`.
`.
`.
`1436
`83
`Solutions, Emulsion5.aQd Suspensions .
`84
`Paregt§r3i_Bmparations"'
`.
`85
`Ophthalmic Preparations ,
`86
`Extraction and Exfractives‘.
`87 Medicated Applications .
`..
`88 Powders.
`.
`.
`'.
`.‘ .
`89 T3Qie1s,rCapsul.es,,and Pil|s—.— .1
`90 Coating of Pharmaceutical Dosage F
`‘91
`"Prolonged-Action Pharmaceuticals .
`Aerosols .
`K
`92
`PART 9
`
`PhannaceuHcalPracHce
`
`93-
`94,
`95
`96
`97
`9a
`99:
`100
`101
`102
`103
`104
`105
`106
`
`.
`.
`.
`.
`.
`The Patient .
`Ambulatory Patient Care .
`Institutional Patient Care .
`Patient Communication .
`The Prescription .
`Drug interactions .
`Utilization and Evaluation of Clinical Drug Literature .
`Surgical Supplies .
`Health Accessories .
`.
`.
`.
`.
`.
`Poison’Contro|.
`.
`.
`.
`Laws Governing Pharmacy.
`Pharmaceutical Economics and Man
`Dental Services‘.
`Veterinary Services .
`
`agement .
`
`PART 10
`
`Appendix
`
`Manufacturers lndex_.
`Alphabetic index .
`
`TEVA PHARMACEUTICALS USA, INC
`
`TEVA EXHIBIT 1030
`. V. MONOSOL RX, LLC
`
`RBP_TEVA05022441
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC
`
`

`
`24 Rheology
`
`rheology ol selecl
`pharmaceutical
`syslems
`viscometers
`
`elastic solids
`Newlonian,
`pseudoplaslic,
`and dilalant
`liquids
`semisolids
`gels
`thixolropy
`flow of disper-
`sions
`viscoelasticily
`
`Hans Scholl,?PhD Professor of Physical and Colloid
`Chemistry, SchoolofPharmacy, Temple University,
`Philadelphia, PA 19140
`
`Fundamentals
`
`The concepts and quantitative aspects of rheology
`are described in this section.
`
`Elastic Solids
`
`When a ball (rubber ball, steel ball bearing, or base-
`ball) is dropped on the floor or hit with a bat, it is
`temporarily flattened. After the impact, the original
`spherical shape is restored. When we pull on a rubber
`band, steel spring, or muscle, they stretch or extend.
`On release, they resume their original length. This
`behavior, characteristic of solids, is called elasticity.
`The force F producing the deformation, or the
`equal and opposite restoring force in the deformed
`solid, divided by the area A over which F is applied, is
`called stress.
`In the stretching process, A is the
`cross—sectional area of the filaments, and the deforma-
`tion is said to be in tension. Other modes of deforma-
`tion are by bending or flexure, torsion, compression,
`and shear. The deformation or strain of the stretched
`filaments, or their elongation, is the difference between
`their length while under tension, L3, and their original
`length, L0, which is equal to the length after the stress
`is released, expressed as a fraction of the original
`length, namely, (L, ~ L0) /L0.
`
`Rheology is the branch of physics which deals with
`deformation and flow of matter.
`It is important in
`many fields. To the physiologist, rheology governs
`the circulation of blood and lymph through capillaries
`and large vessels, flow of mucus, bending of bones,
`stretching of cartilage, contraction of muscles, and
`spreading of the gluteal region when sitting down.
`To the physician, the fluidi_t_y__of solutions to be in-
`jected with hy1)odermic_E'yringes or infused intra-
`venously,
`flexibility of
`tubing used in catheters,
`extensibility of gut, action of fecal softeners, and
`strength of sutures and ligatures are important rheo-
`logical properties. To the pha,r_r_n_ac_ist,_ rheology is
`important in the flow of emulsions through colloid
`mills and pumps, working of Qiritrnents on slabs or
`roller mills, Lrituration of suspensions in mortar and
`pestle, and properties of glass or plastic containers and
`of rubber closures. To the consumer, rheology comes
`into play when he squeezes toothpaste from a col-
`lapsible tube, spreads lotion on his skin or butter on a
`slice of bread or paint on a surface, writes with a pen,
`sprays liquids from atomizers or aerosol cans, chews
`food, hits balls with racket, paddle, hat, or club,
`jumps on a trampolin or off a diving board, swims, and
`lays down in bed and compresses the stuffing and metal
`springs in the mattress.
`From the rheological viewpoint, systems are solid
`if they preserve shape and volume, liquid if they pre-
`serve their volume, and gaseous if neither shape nor
`volume remains constant when forces are applied to
`them. Of the three systems, the transport properties
`of gases, described by the kinetic theory of gases, are
`best understood, but they are of minor importance in
`pharmacy.
`Ideal solids are deformed when stresses are applied
`to them but regain their original shape completely
`when the stresses are released. The ability to restore
`their shape is called elasticity. Similarly, liquids can
`be compressed to somewhat smaller volumes, but
`assume their original volumes when the pressure is
`released. The dividing line between solids and liquids
`is not clear-cut. As explained below, some systems
`which behave as elastic solids when subjected to small
`stresses and/or to moderate stresses of short duration
`will undergo permanent deformation, resembling very
`viscous liquids, if the stresses are larger and/or applied
`for longer periods of time.
`
`The proportionality con-
`e mo u us of elasticity or Young’s
`, ca e
`stant
`modulus,
`is a measure of the stiffness, hardness, or
`resistance to elongation. There is also a modulus of
`shear or rigidity and a compression or bulk modulus.
`Tensile compliance is the reciprocal of Young’s modu-
`lus, or the ratio of strain to stress.
`..In the CGS system, the units of stress are dyne/
`cm” or, since force = mass >< acceleration,
`(g cm/
`sec?)/cm? = g/cm secl. Since strain is dimensionless,
`Young’s modulus has the same dimensions as stress.
`Modulus values for solids important in appliances,
`as packaging materials, and in physiology are listed
`in Table I.
`350
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX LLC
`
`RBP_TEVA05022442
`
`TEVA EXHIBIT 1030
`TEVA PHARMACEUTICALS USA, INC. V. MONOSOL RX, LLC