Handbook of Non-Invasive Drug Delivery Systems. Non-Invasive and Minimally-Invasive Drug Delivery Systems for Pharmaceutical and Personal Care Products

312 Pages·2009·4.45 MB·English

by  Vitthal S. Kulkarni (Eds.)

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British Library Cataloguing in Publication Data
Kulkarni, Vitthal S.
Handbook of non-invasive drug delivery systems.
1. Drug delivery systems. 2. Transdermal medication.
3. Oral medication.
I. Title
615.6-dc22
Library of Congress Control Number: 2009935943
ISBN: 978-0-8155-2025-2
For information on all William Andrew publications visit our
website at elsevierdirect.com
Printed and bound in the United States of America
09 10 11 12 11 10 9 8 7 6 5 4 3 2 1
PREFACE
Topical application of pharmaceuticals has a long tradition in drug delivery
dosage forms; however, it is typically a passive means of skin penetration and
not efficient for systemic drug delivery. Therefore the efficacy of topical drug
delivery is not comparable to that of oral or injectable routes of drug ad-
ministration. The unique advantages of topical drug delivery include local
application, ease of use, and self-administration.Conversely, concerns fororal
dosage forms include nausea and, gastrointestinal upset/stomach irritation,
and repeated doses are often needed whereas concerns for injectable (in-
vasive) dosage forms include pain and fear of injection, and requiring pro-
fessional assistance for drug administration. These concerns exert limitations
on patient compliance for treatment by oral or invasive medication forms.
To reap the potential of topical drug delivery for systemic circulation, it is
necessary to improve the skin penetration of topically applied medicines. This
can be achieved to a limited degree by improving the formulation and to
a greater degree by applying external electromechanical energy for enhancing
skin penetration. Alternatively to the topical/transdermal route of drug ad-
ministration, other routes including nasal, pulmonary, and ophthalmic are
quite effective for entering the systemic circulation without the pain and
concerns of invasive or oral drug delivery routes. Therefore, a medication that
is delivered systemically by routes other than the oral or injectable route are
considered non-invasive or minimally invasive modes of drug administration.
For successful systemic delivery of drugs, a non-invasive route, the require-
ments are efficient electromechanical devices that are safe, easy to use, and
compatible with drug formulation, and affordability for regular use by anyone
in need of treatment. In the past 10 years, significant improvements in drug
delivery device technologies have taken place, making them safe, compatible,
and affordable; consequently, the systemic delivery of drugs by a minimally
invasive or non-invasive route has become a reality. More and more medica-
tions are formulated or reformulated for systemic delivery via topical/trans-
dermal, nasal, pulmonary, and ophthalmic routes. This book aims to review
the current status of a variety of minimally invasive drug delivery systems.
xi
xii Preface
Transdermal drug delivery is a non-invasive system; however, more ef-
ficient drug delivery systems that enhance skin penetration by employing
external devices have shown strong commercial potential. Drug delivery
systems that employ external devices to enhance skin penetration include
ultrasonication, iontophoresis and microneedles, and these devices are
expected to be in common use in the near future. Other systems included in
this book are ophthalmic, nasal, and pulmonary drug delivery systems. The
nasal route has shown potential for bypassing the blood–brain barrier to
deliver drugs to the brain and spinal cord. In addition to the pharmaco-
logical advantages of nasal or pulmonary routes, self-administration, ease of
administration, convenience, and accessibility make these minimally in-
vasive drug delivery systems effective and patients readily comply with the
treatment. Consequently, this route of drug administration has become
popular and is expected to grow its market share in the future.
This book is comprised of 10 chapters that provide readers with thorough
and focused reviews on topical and transdermal emulsions, microemulsions
and nanoparticles, device-aided enhanced skin penetration, and nasal,
pulmonary, and ophthalmic drug delivery systems. Regulatory require-
ments for nasal and pulmonary drug delivery are complex, and include
investigating the compatibility of the formulation with a container-closure
system (CCS) and establishing the stability of the formulation in a complex
CCS, such as pressurized metered-dose inhalers or dry powder inhaler
systems. The last chapter of this book is exclusively focused on the regu-
latory aspects of nasal and inhaled drug products.
The contributors to this book come from both academia and industry,
and provide a wealth of current and thorough information on the topic of
minimally invasive drug delivery systems. I sincerely believe that minimally
invasive drug delivery systems will be in great demand in the near future;
therefore, this topic warrants a thorough review and realization of the po-
tential for this new form of medication. For the first time, an attempt has
been made to review the various minimally invasive drug delivery routes in
this book, which is intended to be read by industrial and academic pro-
fessionals in the area of novel drug delivery. I hope that readers will be
enriched with knowledge of the current and emerging trends of minimally
invasive drug delivery systems and regulatory aspects.
Dr Vitthal S. Kulkarni
EDITOR BIOGRAPHY
Dr Vitthal S. Kulkarni
Scientific Advisor,
DPT Laboratories, San Antonio, TX.
Dr Vitthal S. Kulkarni has been based at DPT Laboratories since 2003 in the
Research and Development Department and leads the preformulation/
research group.
Dr Kulkarni is highly experienced in developing and characterizing
various non-invasive drug delivery systems including topical drug delivery
systems comprised of liposomes, and nano-particles, emulsions and nasal
spray products. After earning a PhD in Chemistry at National Chemical
Laboratory, Pune, India in the area of surface/colloid chemistry,
Dr Kulkarni studied lipid monolayers, bilayers (liposomes), lipid nano-
structures, and protein electron crystallography at various institutions in-
cluding Universite´ de Provence, Marseille, France, JEOL Ltd., Tokyo,
Japan, Vanderbilt University, Nashville, TN, University of Minnesota,
Austin, MN and Yale University, New Haven, CT before moving into
industry.
Dr Kulkarni has been an invited speaker at Drug Delivery Conferences
and he has published several research papers in peer-reviewed journals,
industrial periodicals, and book chapters in the area of lipid bilayers and
monolayers, molecular self-assemblies, liposome technology and topical
drug delivery systems. Dr Kulkarni is also an adjunct faculty member at
San Antonio College and he is an active member of the American Asso-
ciation of Pharmaceutical Scientists and the American Chemical Society.
xiii
CONTRIBUTORS
Dr Mohammed Ali
Mohammed Ali is currently an Assistant Professor in the Department of
Technology at Jackson State University, Jackson, Mississippi, where he is the
Director of the Laboratory for Aerosol and Respiratory Drug Delivery. His
technical articles have been published in 10 peer reviewed journals and
18 national and international conference proceedings in the areas of aerosol
medicine, pulmonary drug delivery and pollution in the workplace envi-
ronment. Dr Ali has received several awards, such as: Research Achievement
Award (2008) from the American Association of Bangladeshi Pharmaceu-
tical Scientists; NIEHS Intramural Research Training Award (2007); Best
Student Research Award (2007) from the Arkansas Society for Public
Health Education; and Alpha Epsilon Lambda (2006). He is the editorial
board member of the AAPS PharmSciTech Journal, Journal of Recent
Patents on Inflammation and Allergy Drug Discovery, and the Journal of
Management and Engineering Integration. Dr Ali is an active member
of the American Association of Aerosol Research (AAAR), American
Association of Pharmaceutical Scientists (AAPS), and the Association of
Technology, Management and Applied Engineering (ATMAE). Other
recognitions and awards bestowed on Dr Ali include Fullbright Scholarship
from the Government of France for Graduate Study at the Asian Institute of
Technology, Bangkok, Thailand (1993); United States National Collegiate
Award (2001) by the US Achievement Academy; Upsilon Pi Epsilon
(2001); and Biltmore Who’s Who in the World (2009).
Priya Batheja
Priya Batheja is a research assistant at the Drug Delivery Laboratory, NJ and
is currently pursuing her PhD in pharmaceutical sciences at Rutgers Uni-
versity, NJ. Post her Bachelors degree in Pharmacy and Masters in Business
Management, she has pursued a career in pharmaceutical sciences with
a focus on drug delivery and formulation development. Priya is an author of
eight publications and two book chapters and is also a co-inventor on
a patent. She is a recipient of a number of awards including the ‘‘Innovative
controlled delivery concept’’ award by the CRS NJ student chapter (2008),
xv
xvi Contributors
‘‘Outstanding Poster’’ at the GRASP (Graduate Research Association
of Students in Pharmacy) 2007, best poster (third place) at the ‘New
Approaches and Technologies in Oral Drug Delivery’’ conference organized
by the New Jersey Chapter of CRS (2009), and the AstraZeneca Travelship
award for the 2008 AAPS Annual Meeting.
Dr James N. Chang
James N. Chang is currently the Chief Executive Officer of TaiMed
Biologics, a biotech company focused on the development of antiviral
drugs. Dr Chang received his doctorate in Chemical Engineering from
the University of Washington in 1986. Prior to his current appointment,
he had a long career in the pharmaceutical/biotech industry working
at Procter & Gamble and Allergan, where he was in charge of formula-
tion development and drug delivery for a number of years. Dr Chang is an
expert in mathematic modeling and polymeric drug delivery systems, and
he has direct experience in taking drug delivery systems from conception,
through development and regulatory approval, to the market place.
Dr Chang is the author of over 30 patents and peer-reviewed papers in
ophthalmic drug delivery. He has also been invited to speak at international
conferences.
Dr Hong Dixon
Hong Dixon is the Senior Research Scientist in the Microencapsulation and
Nanomaterials Department at Southwest Research Institute, San Antonio,
TX. Dr Dixon is focusing on developing novel drug delivery technology,
including targeted and triggered drug delivery, micro- and nano-
encapsulation formulation, and novel polymer and nanocomposite material
synthesis. She holds 12 US and foreign patents.
Mr Dino J. Farina
Dino J. Farina is the Founder and CEO of Proveris Scientific Corporation.
Previously, Mr Farina developed quantitative imaging systems for temper-
ature and fluid flow measurement as a NASA Graduate Student Fellow at
Stanford University and the NASA–Ames Research Center. Mr Farina is
a named inventor on 18 US and international patents related to pharma-
ceutical spray product testing and analysis. Mr Farina is considered an expert
in the field of spray drug product characterization having authored and
co-authored numerous international journal articles and given technical
presentations to the FDA in this field. Farina holds an MS and Master
of Engineering from Stanford University and a BS from Northeastern
University in mechanical engineering.
Contributors xvii
Dr Ping Gao
Ping Gao currently holds a Director position, Global Pharmaceutical and
Analytical Sciences, Abbott Laboratories. He has over 18 years’ working
experience in the pharmaceutical industry. He developed his scientific and
technical expertise in areas including early discovery support and prefor-
mulation, material characterization, formulation sciences and drug delivery
technologies, and commercial scale manufacturing. His long-standing
interest and scientific investigation have focused on physicochemical/
biopharmaceutical properties of drugs, design and development of con-
trolled/extended release dosage forms, enabling drug delivery technologies
for poorly soluble drugs, and in vitro dissolution methods and the in vitro–
in vivo relationship. He has 47 publications including research articles in
peer-reviewed journals and book chapters, and has made 48 podium pre-
sentations at national and international conferences, workshops and short
courses, universities, and the US-FDA. He has 15 US patents and 17 patent
applications pending. He is a member of both ACS and AAPS and was
elected as AAPS Fellow in 2009.
Mr Longsheng Hu
Longsheng Hu is working as a product development scientist at the Global
Topical HealthCare Research and Development Department of Johnson &
Johnson, Morris Plains, NJ. Currently Mr Hu is also part time PhD student
working on iontophoretic transdermal drug delivery systems under the
guidance of Dr Bozena ‘‘Bo’’ B. Michniak-Kohn, at the College of Pharmacy,
Rutgers University, Piscataway, NJ. He has Masters degrees in both Chemical
Engineering and Pharmaceutical Science from the University of Cincinnati.
He has one patent publication. He is a member of AAPS.
Diksha Kaushik
Diksha Kaushik is currently a PhD student in the Department of Phar-
maceutics in the Ernest Mario School of Pharmacy at Rutgers – the State
University of NJ. She holds a Master’s degree in Pharmaceutics as well as
a Bachelor’s degree in Pharmacy from Hamdard College of Pharmacy, New
Delhi, India. She has contributed to several review articles and book
chapters. Her research interests are in the fields of transdermal/topical drug
delivery and the pharmacokinetics of the actives.
Mr Brian Kilfoyle
Brian Kilfoyle is currently a graduate student working towards his PhD in
the Department of Pharmaceutics at the Ernest Mario School of Pharmacy
at Rutgers, the State University of New Jersey. His current research areas
include the optimization of nanosphere-drug formulations as delivery
xviii Contributors
vehicles into and across biological membranes, permeation analysis across
biological and synthetic membranes, and the development of a synthetic
membrane for transdermal testing. Prior to his graduate studies, Brian
worked in the drug delivery field specializing in pulmonary delivery systems
at MicroDose Technologies and Alkermes Inc. and transdermal delivery
systems at MacroChem Corporation.
Mr Michael Ladika
Michael Ladika is the Senior Manager for Institute Business Development at
Southwest Research Institute, San Antonio, TX and is also the Chairman of
the Southwest Research Consortium. Mr Ladika has served on corporate
innovation councils to address technology and business issues requiring
multi-disciplinary, multi-organizations resources. He has led programs in
the research, development, engineering, and production of chemical and
mechanical systems. He holds two US Patents and has 22 classified invention
disclosures.
Dr Robert W. Lee
Dr Lee is Vice President of Pharmaceutical Development at Particle
Sciences Inc. He is responsible for product development at Particle Sciences
as well as providing support to clinical manufacturing operations and
business development. His responsibilities include oversight of formulation
development, drug delivery, analytical sciences, quality control, and quality
assurance.
Before joining Particle Sciences, Rob held senior management positions
at Novavax, Inc., Lyotropic Therapeutics, Inc., and Imcor Pharmaceutical
Co. He holds BSs in Biology and Chemistry from the University of
Washington and a PhD in Physical Bioorganic Chemistry from the
University of California, Santa Barbara.
Rob has published articles in numerous peer-reviewed journals and
three book chapters plus holding 11 issued patents and 14 provisional or
PCT patent applications.
He has more than 18 years of experience in pharmaceutical research and
development of both therapeutic drugs and diagnostic imaging agents. Rob
maintains strong academic ties, including an appointment as Adjunct
Associate Professor of Pharmaceutical Chemistry at the University of Kansas
in 1992, and serving as a reviewer for both the International Journal of
Pharmaceutics and Journal of Pharmaceutical Sciences.
Dr Guang Wei Lu
Dr Guang Wei Lu is currently a Research Fellow in the Parenteral Center
of Emphasis, Pfizer in Groton, CT. His recent interests focus on the
Contributors xix
development of liquid and semisolid formulations, and drug delivery
through topical, transdermal, and ocular routes of administration. Some of
his past positions include Associate Professor at the Shanghai University of
Traditional Chinese Medicine (China); Visiting Scholar at the Medical
School of Osaka City University, Department of Pharmacology (Japan);
Senior/Staff Scientist in Johnson & Johnson Consumer products (USA);
and principal research scientist and associate research fellow at Pharmacia
(USA). Dr Lu has written and published more than 30 research articles,
book chapters, and patent applications. He has also been invited to lecture at
numerous national and international conferences as well as universities. In
2006, he received the Pfizer Global Research and Development Achieve-
ment Award.
Dr Joe McDonough
Joe McDonough is the director for the Microencapsulation and Nano-
materials Department at Southwest Research Institute, San Antonio, TX.
Dr McDonough is currently developing novel drug delivery technology,
including cellular delivery and nano-stabilization. He oversees programs in
ocular, nasal, transdermal, oral and intramuscular delivery, primarily fo-
cusing on micron-and nanoparticle formulations of new and existing
pharmaceuticals. He has 20 years of experience managing research efforts in
pharmaceutical development, including bulk and dose-form manufactur-
ing, regulatory strategy and compliance for filings and licensing of new
chemical entities.
Dr Victor Meidan
Victor Meidan is a lecturer at the Strathclyde Institute of Pharmacy and
BioMedical Sciences (SIPBS) located at Strathclyde University in Glasgow,
Scotland. His main research interest is in the transfer of drugs across
biological barriers, particularly skin and mucosal surfaces. His current
publications include seven book chapters and 30 full-length papers in
internationally recognized, peer-reviewed journals.
Dr Bozena B. Michniak-Kohn
Bozena B. Michniak-Kohn obtained her PhD in Pharmacology from
Leicester Polytechnic, Leicester, UK now renamed the DeMontfort
University. Dr Michniak-Kohn is a tenured Full Professor in Pharmaceutics
at the Ernest Mario School of Pharmacy, Rutgers – the State University of
New Jersey, Piscataway, NJ and is the Director of the Laboratory for
Drug Delivery of the New Jersey Center for Biomaterials (NJCBM).
Dr Michniak-Kohn has directed over 26 PhD students, six Masters students,
and 200+ undergraduates and the work resulted in over 300 abstracts, three
xx Contributors
patents, two books, and more than 100 papers and book chapters. The work
is funded from both federal (NIH/NSF/DoD/US Army Natick/DARPA)
and industrial funds.
Dr Michniak-Kohn is also the US Editor of the Controlled Release
Society Newsletter. She is a Fellow of AAPS and is a reviewer for over
a dozen pharmaceutical and drug delivery journals.
Dr S. Narasimha Murthy
Dr S. NarasimhaMurthy is currently an Assistant Professor of Pharmaceutics
at the University of Mississippi, USA. Dr Murthy obtained his PhD from
BangaloreUniversity, India and completed his post doctoral research training
at Roswell Park Cancer Institute, Buffalo, NY. ‘‘Murthy research group’’
focuses on developing noninvasive drug delivery techniques including
transdermal drug delivery systems. Dr Murthy has about 50 publications in
peer reviewed international journals and has presented several papers in
scientific meetings. His research programs are funded by National Institutes
of Health and Pharmaceutical industries.
Mr Rajiv Sheel
Mr Sheel is Director of US Corporate Development & Strategy for Orgenus
Pharma (a wholly-owned subsidiary of Orchid Pharmaceuticals). He is re-
sponsible for growing Orchid’s footprint in the US via mergers/acquisitions,
joint ventures and product/technology licensing. His responsibilities in-
clude the scientific and commercial evaluation of new products and drug
delivery technologies.
Before joining Orgenus Pharma, Rajiv held key business development
and strategic marketing with Novavax, Inc., ImmunoGen and Smith and
Nephew Plc. He holds a BS in Biological Sciences from the University of
Massachusetts-Lowell and an MBA from Babson College, and received
graduate training in Molecular Neurobiology from MIT.
He has more than 12 years of experience in commercial evaluation,
planning and launch of new products and technologies in the pharma-
ceutical, biotech &medical device industries and has significant background
in the selection and pursuit of new applications for novel technologies.
Dr Dinesh B. Shenoy
Dr Shenoy is General Manager – Formulation Development, at Cadila
Pharmaceuticals Ltd (CPL), India. He is responsible for product de-
velopment (for both pharmaceuticals and biologicals) at CPL – with a focus
on innovative and novel delivery systems.
Before joining CPL, Dr Shenoy worked as Director (Formulation
Development) at Novavax, Inc., where he worked on development and