IPR2023-00512
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`CELGENE 2065
`APOTEX v. CELGENE
`
`

`

`
`
`

`

`Ansel's
`Pharmaceutical
`Dosage Forms and
`Drug Delivery Systems
`
`EIGHTH EDITION
`
`

`

`
`
`

`

`EIGHTH EDITION
`
`Loyd V.Allen, Jr., PhD
`Professor and Chair Emeritus
`Department of Medicinal Chemistry and Pharmaceutics
`College of Pharmacy
`University of Oklahoma
`Editor-in-Chief
`
`International Journal of Pharmaceutical Compounding
`
`Ansel's
`Pharmaceutical
`Dosage Formsand
`Drug Delivery Systems
`
`Buenos Aires « Hong Kong = Sydney = Tokyo
`
`Nicholas G. Popovich, PhD
`Professor and Head
`
`Department of Pharmacy Administration
`College of Pharmacy
`University of Illinois at Chicago
`
`Howard C. Ansel, PhD
`Professor and Dean Emeritus
`College of Pharmacy
`The University of Georgia
`
`A Wolters Kluwer Company
`Philadelphia = Baltimore + Mew York + London
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`Allen Ir. Nicholas Ca
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`forms and drag delivery systems / Howard C. Ansel, Loyd V
`af Pharmaceutical d Same
`cl999
`Nicholas G. Popovich. 7th ed.
`Jr..
`Allen,
`Includes biblic et api al relerences and index
`ISBN
`17
`-4612-4
`age forms:
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`gence, or otherwise) lor any injury
`(asa matter of product liability, 1
`Che publisher is not responsible
`resulting from-any material
`contained herein, This publication contains informationrelating to general
`principles of medical care
`that should nor be construed as specific
`instructions lor
`individual patients
`Manufacturers’ product information and package inserts should be
`reviewed for current information,
`in
`chiding Contraindications,
`dosages, ard precautions
`
`12345678910
`
`2. Drug delivery
`Nicholas ts
`Sand drug
`Drug De live Ty SV¥SLEI
`
`Tithe:
`system:
`|. Ansel, Howard
`
`Pharmaceutical dosage forms and drug
`lo33— 1V. Ansel, Howard ¢
`
`SL aD i276
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`is to introduce pharmacy students to the principles and
`The purposeof this text
`technologies applied in the preparation of pharmaceutical dosage forms and drug
`delivery systems, An integrated presentation is used to demonstrate theinterrela-
`tionships between pharmaceutical and biopharmaceutical principles, product de-
`sign, formulation, manufacture, andthe clinical application of the various dosage
`forms in patient care. Regulations governing the manufacturing and compound
`ing of pharmaceuticals are also presented
`As has beenthe hallmark of this textbook since its first edition more than 30
`years ago, cach chapter is written ata level consistent with the requirements ofstu-
`dents being introduced to this area of study, Because this textbook often is used
`early in the professional curriculum,
`it contains important introductory topics,
`such as the historical development of drugs and pharmacy, the role of
`the phar-
`macist in contemporary practice, standards of
`the United States Pharmacopeia-—
`National Formulary, systems and techniques of pharmaceutical measurement,
`pharmaceutical and biopharmaceutical principles applicable to drug product de-
`velopment, current good manufacturing practice and current good compounding
`practice standards, and the regulatory process by which pharmaceuticals are ap-
`proved for marketing by the federal Food and Drug Administration
`
`A Gutde co the Climcal Experience, 2nd ed. Baltimore
`
`Introduction to the SOAP Format for Case Studies?
`
`The most commonly used documentation format for case studies is referred to by
`the mnemonic SOAP, which stands for Subjective information, Objective infor-
`mation, Assessment, and Plan
`
`1Adapted with Pinion irom t Sullivan TA, Witthowsky AK. Clinical drog
`Practice Manual:
`
`Preface
`
`The Eighth Edition
`The eighth edition presents a signihcant rewrite of some of the sections of the pre-
`vious edition, We have reorganized the book into eight divisions, containing 20
`chapters, based upon traditional pharmaceutic pedagogy, This allows the system-
`atic presentation of dosage forms according to their physical form and character-
`istics. The Physical Pharmacy Capsules introducedin the sixth edition continue
`to emphasize important underlying pharmaceutical principles. Also continuedin
`this edition is the Chapter at a Glance at the beginning of each chapter
`Other important changes:
`
`Enhanced considerations of dosage form design and formulation
`[wo case studies (one pharmaceutical and one clinical) in each of the dosage
`form chapters (see
`“Introduction to the SOAP Format for Case Studies,”
`next)
`An updateof the current good compounding practices
`Expanded clinical considerations in the use of the dosage lorms
`Twonew glossaries in the appendix, onelisting dosage forms and one listing phar
`maceutical terms, back asa result of numerous requests of students and faculty
`
`

`

`The content of a SOAP note written by a pharmacist will be slightly different
`from that written by another type of health care provider, primarily in the assess-
`aks
`\
`;
`ment section; a pharmacist’s SOAP note will primarily identify problems of diag-
`ThOSsiS
`Before a SOAP note is begun, the following must be clearly defined:
`
`What are the patient's most important problems that must be addressed and/or
`resolved now?
`What is the evidence that each problem exists?
`What are the therapeutic goals and options for each problem?
`
`Preface
`
`the therapeutic outcome
`
`The answers to each of these questions will form the content of the assessment
`section of the SOAP note, Therefore, the assessment is written mentally before the
`actual SOAP note is begun. After the problems are defined, subjective and objec-
`tive information needed to justify why those problems exist should be written
`down
`Thefirst paragraph begins with “S:” and contains subjective information, which
`is obtainedfromthepatient interview. Examples of subjective information include
`patient-prov ided infor mation about disease Sy plots over-l hi -COunter medica
`tions, drug allergy descriptions, and compliance
`The second paragraph begins with “O:" and contains objective information ob-
`tained by physically examining the patient, reading laboratory data, checking pre-
`scription records for doses and refill patterns, locating medication costs from a
`printed or on-line formulary, and so on. Someinformation can be either subjec-
`tive or objective, depending on howit is obtained. The most important thing to
`remember when composing the subjective and objective portions of notesis that
`only information pertaining directly to the assessment should be included
`The third paragraph begins with “A:” and contains the pharmacist's assessment
`of the patient's medical and pharmacologic problem or problems.
`If the subjective
`and objective paragraphs are written well, the problem should be obvious to the
`reader, Other types of information included in the assessment paragraph are the
`therapeutic goals and abrief discussion of the therapeutic alternatives
`The fourth paragraph begins with either “P:” or “R:" anddetails either-a plan
`(P), or recommendation (R), whichever is more appropriate for thesituation. The
`plan should include individualized instructions (drug by generic name, dose,
`route, frequency, and when applicable, duration of therapy). The exact dose and
`frequency should be identified
`Also,
`the monitoring plan must be detailed, including specifically what (e.¢.,
`laboratory test, symptom) should be measured, who should measure it (patient,
`caregiver, pharmacist), when and how frequently the measuring should occur, and
`at what point changing therapy will be considered. A backup plan for use in the
`event of therapeutic failure should also be noted here. Finally,
`instructions for the
`proper useof prescribed medication or medications should be included to enhance
`
`

`

`Acknowledgments
`
`clinical case for Chapter 18
`
`lLacknowledge with grateful appreciation the major contributions and foresight of
`Howard C. Ansel,
`the originator of the textbook, whose guidance and hard work
`overthe years havesignificantly contributed to the education of
`tens of thousands
`of pharmacists worldwide, Deep appreciation to Nicholas G. Popovich for his ex-
`tensive contribution to this textbookin clinical pharmacy and pharmacy practice
`and his unique ability to present the integrated approach used in this work, To-
`gether, we extend our gratitude to students and academic colleagues who have
`shared their thoughts with us on this revision: we hope that we have been su
`cessful in responding to their thoughtful suggestions. We also acknowledge with
`appreciation our colleagues in industry who have generously provided scientific
`and technical information and updated figures and photos for our use
`We gratefully acknowledge the following individuals who contributed to the
`development of this book through their critiques,
`review, and suggestions of the
`individual chapters. Chapter 15 (Parenterals): Jane A. Gottlieb, RPh; David Don
`ley RPh, Manager of the Pharmacy Department at Clarian Health, |
`ndianapolis,
`Indiana; and Mary Baker, PharmD, MBA, Senior Medical Manager, Global Med-
`ical Affairs, Hospira,
`Inc, Chapter
`16 (Biologics): Mary
`Ann Kliethermes,
`PharmD, Pharmacotherapist, Clinical Assistant Professorof the Ambulatory Care
`Pharmacy and Manager of the Refill-10 Program of the Pharmaceutical Care Cen-
`ter: and Leslie Ann Briars, PharmD, Clinical Assistant Professor and Pediatri:
`Clinical Pharmacist of Ambulatory Care Pharmacy Services at the University of
`Illinois at Chicago. College of Pharmacy. Chapter
`18 (Radiopharmaceuticals)
`Dan Murphy, RPh, Regional
`Pharmacy Compliance Specialist, West Hartford,
`Connecticut; Peter Sposato, RPh, Pharmacy Managerat Syncor International Cor-
`poration, Glastonbury, Connecticut, and Louis Juliano RPh, Senior Director ol
`Operations, Northeast at
`the Cardinal Health Nuclear Pharmacy Services, Kings
`Park, New York.
`In addition, we thank the following formerdoctoral students at
`the University of Illinois at Chicago College of Pharmacy and Purdue University
`School of Pharmacy and Pharmacal Sciences for
`their critiques,
`review, and sug-
`gestions of the individual chapters. They are Raool R. Abdellatil, PharmD; Nancy
`J. Costlow, PharmD; Paul 8. Djuricich, PharmD; Huzefa H. Master, PharmD; Mary
`E. Kiersma, PharmD: and Jennifer Thomas, PharmD
`A number of for-
`Newto this edition are the dosage form chapter case studies,
`mer doctoral students at the Universityof [linois at Chicago College of Pharmacy
`and the Purdue University School of Pharmacy and Pharmacal Sciences prepared
`the clinical case studies, and wesincerely appreciate their contribution to the text
`Those participating and the chapters in which their cases appear are as follows
`Chapters 6 and 9, Yamini Shah, PharmD; Chapters 7 and 8, Sumi Patel, PharmD
`Chapters 10 and 11, Rebecca L. Roche, PharmD, Chapter
`12 Malisa H, Patel
`PharmD; Chapter 13, Kristin M. Hurt, PharmD; Chapters 14 and 17, Kristin M
`Hurt PharmD and Malisa H. Patel, PharmD; Chapter
`15, Natalie
`Y. Vazzana,
`PharmD, and Elizabeth Chu, PharmD; and Chapters 16 and 19,
`James Song
`PharmD. Nicki L. Hilliard, PharmD, MSHA, BCNP, PAPhA, Associate Professor ol
`Nuclear Pharmacy-at the University of Arkansas Coll pe of Pharmacy, created the
`
`

`

`LoYD V. ALLEN,
`
`|R
`
`Acknowledgments
`
`We especially thankthestaff at Lippincott Williams & Wilkins who have con
`tributed so expertly to the planning, preparation, and production of this newedi-
`tion: David Troy, Matt Hauber, Samantha Smith, and Jennifer Ajello
`
`Edmond, Oklahoma
`
`

`

`Pretace
`Te
`Acknowledgments
`List of Physical Pharmacy Capsules
`
`Section |. Introduction To Drugs, Drug Dosage Forms, and Drug Delivery Systems
`Introduction to Drugs and Pharmacy
`NewDrug Development and Approval Process
`Current Good Manufacturing Practices and Current Good
`Compounding Practices
`
`Section Il. Drug Dosage Form and Drug Delivery System Design
`4 Dosage Form Design: Pharmaceutical and Formulation Considerations
`2
`Dosage Form Design: Biopharmaceutical and Pharmacokinetic Considerations
`
`#2
`.\
`. 142
`
`
`
`7 Feteseetat greta cata eaareen GiaCapsules .... yl cellen sional 204
`
`
`
`20 Novel Dosage Forms and Drug Delivery Technologies
`
`SectionIll. Solid Dosage Forms And Solid Modified-Release Drug Delivery Systems
`6
`Powders and Granules
`186
`
`
`
`
`
`
`8
`Jablets
`227
`§
`Solid Oral Modified-Release Dosage Forms and Drug Delivery Systems
`260
`
`Section IV. Semisolid Dosage Forms and Transdermal Systems
`10 Olintments, Creams, and Gels
`11.)
`«Transdermal Drug Delivery Systems
`
`Section V. Pharmaceutical Inserts
`12
`Suppositories andInserts
`
`Section VIL. Liquid Dosage Forms
`13.
`Solutions
`143Disperse Systems
`
`Section VIL Sterile Dosage Forms and Delivery Systems
`15
`Parenterals
`16
`Biologics
`17
`Special Solutions and Suspensions
`
`Section VIII. Novel and Advanced Dosage Forms, Delivery Systems, and Devices
`18 Radiopharmaceuticals
`..
`:
`aes
`19
`Products of Biotechnology
`
`ne
`
`570
`600
`
`

`

`Contents
`
`Glossary of Pharmaceutical Terms
`
`Appendices
`4 Detinitions of Sélected Brua Cate
`
`Systems and Techniques of Pharm
`
`

`

`Glossaryof
`maceuticalTerms
`
`Appendix
`
`Active Ingredient: the ingredient or ingredientsof a
`pha PmMace wth produe I respo
`for iis nhur
`macologic activity (also
`iment, drug sub-
`stance, active pharmaceutical
`ingreciient)
`Aerosol: a dosage form that is packaged under pres
`stire and contains therapeutically active ings
`ents that are released upon activation of an ap-
`propriate valve system
`Ampul: a final containerthat is all glass in which the
`open end, after All ne with product, iss aled by
`heat (also ampoule, ampule,
`[Fr
`hl] carpule)
`Aseptic:
`lacking disease-producing microorgan
`ISIS; MOL the same as sterile
`Aseptic Processing; manufacturing dosage forms
`without terminal sterilization. The dosage form
`is sterile-hiltered, then aseptically filled into the
`final package andaseptically sealed
`Bead: a solid dosage form in thi
`shape of a small
`SPoere The do Sage form penerally contains mul
`tiple beads (also pellet)
`Bolus: a large, long tablet
`bon to animals
`
`intended for adminis
`
`only
`
`a two-phase system in which one li
`Emulsion:
`is dispersed throughout
`another
`|
`form of small droplets
`Excipient an inactive inerecient of a dosape form
`Extract:
`a concentrated preparation of vegetable OF
`animal drug obtained by
`removal of
`the
`active
`constituents with suitable menstrua, by evapora
`tion of all or nearly all of the solvent and by ad-
`Capsule a solid dosage form in which the drug is
`jusiment of the residual mass or powder to the
`enclosed within a hard or soft soluble containet
`prescribed standards
`or shell
`Fluidextract: a liquid preparation of a vegetable drug
`apsule, Delayed-release: a coated capsule or more
`containing alcohol as.asolvent, preservative. or both
`commonly encapsulated granules that may be
`ind so mace that unless otherwise specified in an in
`coated to resist releasing the drugin the stomach
`dividual monograph,
`each milliliter contains the
`because the drug will
`irritate gastric mucosa o1
`therapeutic constituents of|¢ of the standard drug
`gastric fluid will inactivate the drug
`Foam: an emulsion packaged
`in a pressurized aerosol
`is formu
`apsule, Extended-release:
`a capsule that
`ontainer that has a fluffy,
`semisolid consistency
`lated in such a manner a5 to make the contained
`when dispensed
`medication available
`over an exte
`d period
`a semisolid system onsisting of cither a sus-
`follow ing ingestion
`ension of small inorganic particles or
`large or
`form in which
`-apsule, Soft-shell:
`a solid dosage
`ganic molecules interpenetrated by a liquid
`one or more active ingredients, normally in solu
`Granules: a preparationof dry aggregates of powder
`tion or suspension or
`in the form of
`a paste,
`ts
`partic LES that May CONLIN One OF MOLE active in-
`hued into a one-piece shell
`erecdients with or without other
`ingredients
`ollodion: a liquid preparation composed of pyrox
`Implant:
`see pellet.
`a small sterile solid mass con-
`ylin dissolved in asolvent mixture of alcohol and
`sisting of a highly purified drug with or without
`ethe r and appli d externall,
`excipients made by compression or molding and
`Concentrate for Dip:
`a preparation containing one
`put in pl
`njéction or incision
`or more active ingredients usually in the form of
`Infusion, Intramammary
`nsion of a driig in
`a suitable oil vehicle;
`intended for veterinary use
`aste or solution; it is used to prepare a
`ited
`ension, emulsion, or salution of
`th
`
`of
`
`ingredient(s) for the prevention and treatment
`toparasitic infestations of animals
`Cream:
`a
`se misolicl d
`form ee hlaining one Or
`more drug substan es dissolved of disne red ina
`suitable base
`ot SUSPension
`Drops, Oral:
`a solution, emulsion,
`hat
`is administered in small volumes.
`such as
`drops, by meansof a suitable device
`Effervescent: a dosage formcontaining ingrechents
`that rapidly release carbon dioxide when in con-
`tact with water
`
`Elixir:
`
`pleasantly Mavored. swee
`a clear,
`liquid containing dissolved
`alcoholic
`lients intended for oral us
`
`Gel:
`
`

`

`sell-contained, discrete
`
`lease, extended release, pulsatile release, targeted
`release anc $0 071
`Molded Tablet:
`a
`tablet
`that has been formed by
`dampening the
`ingredients and pressing them
`into a mold,
`then removing and drying the re-
`sulting salid mass
`Mouthwash: an aqueous solution used to rinse the
`oral cavity
`Ointment: a semisolid preparation intendedfor exter-
`nal application to the skin or mucous membrane
`Ophthalmic Preparation: drug in dosage formin-
`tence d to be applied ty the tye
`Ophthalmic Ointment: a sterile ointment intended
`lor applix alhon to the eve
`Ophthalmic Solution: a sterile solution, essentially
`free from foreign particles, suitably prepared anc
`packaged for instillation into the eye
`Ophthalmic Suspension: a sterile liquid prepara-
`tion containingsolid particles dispersed in a lig-
`uid vehicle intended for application 16 the eve
`Ophthalmic Strip: a sterile single-use comtatner or
`Steric impregnated paper STrLp COMIN the
`drug to be applied to the eye
`Orally Disintegrating: a solid oral dosage form that
`disintegrates rapidly in the mouth tofacilitate re-
`lease of the active ingredient
`tic Solution: a solution intended Lor instillation In
`the outer ear
`
`682
`
`Appendices
`
`Inhalation: a solution or suspension of one or mor
`drug substances administeredbythe nasal or oral
`respiratory route for local or systemit effect
`Injection: a preparation intended for parenteral ad-
`ministration oT lor constituting or dilut In? @ Pal
`enteral article prior to administration
`Irrigation:
`a sterile solution intended to bathe or
`lush open wounds or body cavities
`Jelly: st gel
`Liniment: an alcoholic or oleaginous solution of
`emulsion applied by rubbing on the skin tor treat-
`ing pain and stiffness of underlying musculature
`Lotion: a fluid suspension or emulsion applied to the
`surlace of the skin. See solution or suspension
`Lozenge: a solid preparation that is intended to dis
`solve or disintegrate slowly in the mouth
`Lyophilization: removal of water or other solvent
`[rom a frozen solution by sublimation causedby
`a combination of
`temperature
`and pressure dil
`ferentials { alsa ITeeze dry Ing}
`the active in-
`Modified Release: a release pattern of
`greclient from the dosage form that has been de
`liberately changed from that of the conventional
`form.
`Includes accelerated rele
`delayed re-
`
`liquid preparal OT Con ining
`One SUSpPension: a
`micronized particles intended for
`instillation in
`the outer eat
`
`Paste: a semisolid dosage [orm that contains one o1
`more crue substances intended for topical appit-
`cation.
`It generally contains a high concentration
`of solids and has a stiff consistency
`Pellet: see bead. (Alsoa solid granule or regular shape
`prepared by compaction or by granulation.)
`Pill: a solid spherical dosage form, usually prepared
`by a wet massing technique
`Flaster: a solid or semisolid mass supplied on a
`backing material and intended to provide pro
`longed contact with the skin
`Powder: an intimate mixture of dry, finely divided
`drug and/or chemicals that may be intendedfor
`internal (oral) or external (topical) use.
`Premix; a mixture of one or more drug substances
`with a suitable vehicle
`Pulsatile Release: a release pattern of the active i
`gredient fromthe dosage form that is modified to
`release aliquots of the total dose at
`two or more
`time intervals
`
`Rinse: a solution used to cleanse by flushing.
`Shampoo: il solution emulsion, Or LS pe NS hon used
`to clean the hair and scalp
`Soap: the alkali salt(s) of one or morefatty acids
`Solution: a liquid preparation that contains one oF
`more dissolved (molecularly dispersed) chemi
`cal substances in a suitable solvent
`or mixture
`
`of miscible solvents: may be oral, topical, otic
`ophthalmic
`Spirit: an alcoholic or hydroalcoholic solution of
`volatile substances prepared usually by simple
`solution or by admixture of the ingredients
`Sterile: completely lackingliving (viable) microbial
`lite
`Sterility: an ace eptal ly high level of probability that
`a product processed in an aseptic system does
`not contain viable MicToorganisms
`Stick: a slender, cylindrical dosage form of
`consistency,
`
`rigid
`
`Suppository: a solid body adapted tor introduction
`inte the rectal, vaginal, or urethral orihce.
`Suppository Tablet or Insert: a vaginal suppository
`prepared by compression of powdered materials
`into.a suitable shape: can also be prepared byen-
`capsulation in soft gelatin
`Suspension:
`a
`liquid preparation that consists of
`d particles dispersed throughout
`a
`liquid
`phase in which theparticles are not soluble; may
`be oral,
`topical, otic ophthalmic
`Syrup: a solution containing a high concentration of
`sucrose or other sugars. See solution
`System:
`a dosage form developed to allow for
`uniform release or
`targeting of drugs to the
`body
`
`System, Transdermal:
`
`a
`
`

`

`Appendix B * Glossary of Pharmaceutical Terms
`
`683
`
`is designed to deliver drug(s)
`dosage form that
`thravigh the intact skin to the systemic circulation,
`System, Ocular: a dosage form intended for place-
`#
`ment
`in the lower
`‘conjunctival
`fornix,
`from
`which the drugdiffuses through a membraneat
`a constant rate
`
`system, Intrauterine: a systemthat is intended for
`release of drug over a long period, such as a4 year
`Tablet: a solid dosage form containing medicinal
`substance(s) with or without diluents
`Tablet, Chewable: a tablet formulated so that it may
`be chewed, producinga pleasant-tasting residue
`thatis easily swallowed and does not leave:a hit-
`ter or unpleasant altertaste.
`Tablet, Delayed-release: a tablet with a coating that
`is intended to postpone release of the medication
`until the tablet has passed through the stomach
`Tablet, Extended-release:
`a tablet that is formulated
`50) as to make the contained medication available
`over an extended period following ingestion
`Targeted Release: release of
`the active ingredient
`from a dosage form modified to preferenti ally de
`liver most of the drug toa specific region, organ
`or tissue
`
`Transdermal Delivery System, High Velocity Pow-
`der Particles:
`a transdermal drug delivery system
`using supersonic shock waves of helium gas to
`enhance drug diffusion throughthe skin
`Transdermal Delivery System,
`lontophoresis: a
`transdermal drug delivery system enhanced by
`the use of applied electric current
`to facilitate
`drug diffusion through the skin
`a
`Transdermal Delivery System, Phonophoresis:
`transdermal drug delivery system enhanced Dy
`the application of
`low-frequency ultrasound to
`facilitate drug diffusion through the skin (alsa
`ultrasound, sonophoresis, ultrasonophoresis, ul
`traphonophoresis)
`a transdermal matrix
`Transdermal Matrix Patch:
`SYSLEM Using a polymeric Matix containing drug
`intendedfor systemic delivery through the skin;
`generally the skin is the rate-controlling mem
`brane for drug diffusion
`Transdermal MembranePatch: a wansdermal system
`COM CLE a org PeseTVolr entrapped berween
`backing and adhesive layers and a drug diffu
`sion—coniralling membrane; the reservoir is usu
`ally a semisolid dispersion or solution of the drug
`Treche: see lozenge
`Urethral:
`a dosage form intended for insertion inta
`the urethra to providea local effect of the active
`ingredient
`Validation: 5
`‘jentific study to prove that a process
`Is doing what it
`is SLIP py sed to do and js under
`contral
`
`substances
`
`a process used to produce
`Terminal Sterilization;
`sterility in a final product contained in its final
`packaging system
`Tincture: an alcoholic or hydrealcoholic solution
`prepared from vegetable materials or from chem
`ical substances
`Transdermal Delivery System, Electroporation: 2
`transderm:. delivery system enhanced bythe ap-
`plication of short, higsh-voltage electric pulses to
`creale AQUEOUS |pores mM the lipid bilayer cil skin
`and thereby facilitate drug diff
`
`Water, Aromatic: a clear, saturated aqueous solu-
`tion (unless otherwise specified) of one or
`more volatile oils or other aromatic or volatile
`
`