Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs. Formulation Challenges and Potential Benefits

274 Pages·2017·12.854 MB·English

by  Bojan Čalija (Eds.)

Microsized and Nanosized
Carriers for Nonsteroidal
Anti-Inflammatory Drugs
Formulation Challenges and Potential Benefits
Edited by
Bojan Cˇalija
Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade,
Belgrade, Serbia
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List of Contributors
Bojan Čalija, Department of Pharmaceutical Technology and Cosmetology, Faculty of
Pharmacy, University of Belgrade, Belgrade, Serbia
Nebojša Cekić, Faculty of Technology, University of Niš; R&D Sector, DCP Hemigal,
Leskovac, Serbia
Aleksandra Daković, Institute for the Technology of Nuclear and Other Mineral Raw
Materials, Belgrade, Serbia
Ljiljana Đekić, Department of Pharmaceutical Technology and Cosmetology, Faculty
of Pharmacy, University of Belgrade, Belgrade, Serbia
Sanela M. Đorđević, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Tanja M. Isailović, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Jelena Janićijević, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Danina Krajišnik, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Ana Micov, Department of Pharmacology, Faculty of Pharmacy, University of Belgrade,
Belgrade, Serbia
Jela Milić, Department of Pharmaceutical Technology and Cosmetology, Faculty of
Pharmacy, University of Belgrade, Belgrade, Serbia
Caroline O’Sullivan, Department of Process, Energy & Transport Engineering, Cork
Institute of Technology, Cork, Ireland
Uroš Pecikoza, Department of Pharmacology, Faculty of Pharmacy, University of
Belgrade, Belgrade, Serbia
Marija Primorac, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Snežana D. Savić, Department of Pharmaceutical Technology and Cosmetology, Faculty
of Pharmacy, University of Belgrade, Belgrade, Serbia
Radica Stepanović-Petrović, Department of Pharmacology, Faculty of Pharmacy,
University of Belgrade, Belgrade, Serbia
ix
x List of Contributors
Marija N. Todosijević, Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Maja Tomić, Department of Pharmacology, Faculty of Pharmacy, University of
Belgrade, Belgrade, Serbia
Sonja Vučen, School of Pharmacy, University College Cork, Cork, Ireland
Editor Biography
Bojan Čalija was born in Sarajevo (Bosnia and Herzegovina). He graduated
from the Faculty of Pharmacy, University of Belgrade in 2007. In 2013, he
received his PhD in Pharmaceutical Technology at the Faculty of Pharmacy,
University of Belgrade with his PhD thesis entitled “Functionality of chitosans
in formulation of alginate–chitosan microparticles as carriers for nonsteroidal
antiinflammatory drugs.” He completed postgraduate academic specialist stud-
ies in Industrial Pharmacy at the Faculty of Pharmacy, University of Belgrade
in 2015.
During his Master’s and PhD studies, he was awarded with the scholar-
ships of the Ministry of Science and Technology of Republic of Srpska and the
Ministry of Education and Culture of Republic of Srpska. In 2009, as a DAAD
scholar, he was a guest researcher at the Department of Pharmaceutical Tech-
nology at the University of Technology Carolo-Wilhelmina in Braunschweig
(Germany).
Since 2007, Bojan Čalija has been employed at the Faculty of Pharmacy,
University of Belgrade as a teaching associate, teaching assistant, and assistant
professor within the Department of Pharmaceutical Technology and Cosme-
tology. His teaching activities are involved in the Integrated Academic Stud-
ies for Pharmaceutical Technology I, Pharmaceutical Technology II, Novel
Pharmaceutical Dosage Forms, as well as Doctoral Studies in Pharmaceutical
Technology and Specialist Studies in Industrial Pharmacy and Pharmaceutical
Technology.
From 2008 to 2010, he was engaged in the national project of technologi-
cal development: “Development and characterization of colloidal carriers for
nonsteroidal anti-inflammatory drugs.” Since 2011, Bojan Čalija has partici-
pated in the national project of technological development: Development and
characterization of micro and nano drug delivery systems for nonsteroidal
anti-inflammatory drugs” and in the project of basic research: “Synthesis of
molecules with anti-inflammatory and cardio protective activity: structural
modifications, modeling, physicochemical characterization and formulation-
al investigation.” From 2010 through 2012, he was engaged in the interna-
tional Tempus project: “Postgraduate Qualification in Pharmacy—The Way
Forward.”
His research is focused on formulation and characterization of polymeric
microparticulate drug carriers.
xi
xii Editor Biography
Bojan Čalija is the author or the coauthor of more than 70 original articles,
professional papers, and short communications papers. He is a peer reviewer for
several international scientific journals.
He is the coauthor of one textbook in the field of Pharmaceutical Technol-
ogy, one workbook, and one multimedia publication in the field of Industrial
Pharmacy.
Preface
In recent decades, various drug carriers have been developed to overcome
limitations associated with use of conventional drug delivery systems, such as
low bioavailability, insufficient stability, high drug plasma fluctuations, lack of
selectivity for target tissues, frequent administration, and low patient compli-
ance. Owing to their tailorable properties and small size, micro- and nanosized
entities are nowadays the most intensively investigated drug carriers. Rapid
expansion of research in this field has been driven by utilization of materials
with improved functional properties, along with employment of innovative
preparation and characterization techniques.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most com-
monly used groups of medications worldwide. These drugs are widely used for
the treatment of pain, inflammation, fever, and thrombosis. However, their use
is related to some serious gastrointestinal, cardiovascular, and renal adverse
effects. Some of these drugs have short half-lives, so frequent administration is
required to maintain optimal blood concentration levels for a longer period of
time. Limited absorption and low bioavailability are also frequently related to
the oral administration of some NSAIDs. Encapsulation/entrapment of NSAIDs
in micro- and nanosized carriers could be used to overcome these limitations.
Nevertheless, development of a drug carrier with desirable characteristics is
a complex process involving selection of appropriate encapsulation/entrap-
ment material, encapsulation/entrapment procedure, and adjustment of optimal
encapsulation/entrapment conditions. Only careful selection of encapsulation/
entrapping materials and techniques with respect to the structure, physicochem-
ical, pharmacodynamic, and pharmacokinetic properties of the drug, and the
route of administration may result in the overall improvement of the therapeutic
efficacy of NSAIDs.
This book gives the reader a comprehensive overview of formulation strate-
gies of different micro- and nanosized carriers intended for oral, dermal, and
transdermal administration of NSAIDs in one resource, including particulate
carriers (microparticles, nanoparticles, and porous inorganic materials) and soft
colloidal carriers (microemulsions and nanoemulsions). It also discusses the
latest research on advances and limitations of both micro- and nanosized drug
carriers and NSAIDs. Special attention is paid to the functionality of polymers,
silica-based materials, and natural surfactants as potential excipients for micro-
and nanosized drug carriers.
xiii
xiv Preface
Practical solutions for improving overall therapeutic efficacy of NSAIDs
have been included throughout this book and may also apply to the formula-
tion of micro- and nanosized carriers containing other drugs that exhibit simi-
lar physicochemical, biopharmaceutical, and pharmacokinetic characteristics.
Therefore, we hope this book will serve as a useful resource for graduate stu-
dents, professors, and researchers in the pharmaceutical sciences, especially in
Pharmaceutical Technology.
Bojan Čalija
Department of Pharmaceutical Technology and Cosmetology,
Faculty of Pharmacy, University of Belgrade,
Belgrade, Serbia
Chapter 1
Clinical Uses of Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs) and Potential Benefits
of NSAIDs Modified-Release
Preparations
Maja Tomic´, Ana Micov, Uroš Pecikoza, Radica Stepanovic´-Petrovic´
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
1.1 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
The first record about the use of decoctions/extracts of willow bark/leaves for
musculoskeletal pain was 3500 years ago in the Ebers papyrus. Hippocrates,
Celsus, Pliny the Elder, Dioscorides, and Galen all recommended decoctions of
parts of willow and other plants containing salicylate for rheumatic pain and/or
fever. Salicylic acid was isolated in 1836 (by Pina) and synthesized in 1860 (by
Kolbe). The first nonsteroidal anti-inflammatory drug (NSAID)—acetylsalicylic
acid, was synthesized in 1897 (by Hoffmann) in an attempt to improve palat-
ability of salicylic acid. Acetylsalicylic acid was the first drug tested in animals
in an industrial setting, and after human studies it was marketed as aspirin in
1899 (Brune and Hinz, 2004; Vane, 2000).
At the present time, there are more than 50 different NSAIDs on the global
market (Rang et al., 2015b). They are the most frequently used medications for
their analgesic, anti-inflammatory, and antipyretic therapeutic properties, and
aspirin also for its antiplatelet/cardioprotective action. Their wide use could be
illustrated by the data that in the United States in 2010 more than 29 million
adults (12.1%) were regular NSAIDs users (used NSAID at least 3 times per
week for more than 3 months) and around 43 million adults (19.0%) were regu-
lar users of aspirin. Compared with 2005, an overall increase of 41% in NSAID
use and 57% in aspirin use was observed (Zhou et al., 2014).
Microsized and Nanosized Carriers for NSAIDs. http://dx.doi.org/10.1016/B978-0-12-804017-1.00001-7
Copyright © 2017 Elsevier Inc. All rights reserved. 1
2 Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs
1.1.1 Classification and Mechanism of Action
1.1.1.1 Classification
NSAIDs are traditionally classified by their chemical structure on derivatives of
salicylic acid (e.g., aspirin), acetic and phenylacetic acids (e.g., indomethacin,
ketorolac, diclofenac), propionic acid (e.g., ibuprofen, ketoprofen, naprox-
en), fenamic acid (e.g., mefenamic acid), and enolic acid (e.g., piroxicam,
meloxicam) (Table 1.1). After the development of the selective cyclooxygen-
ase (COX)-2 inhibitors, the classification according to the relative inhibition
of COX isoenzymes emerged and became widely accepted (FitzGerald and
Patrono, 2001; Frölich, 1997; Hawkey, 1999). According to this criterion
NSAIDs are classified into nonselective, traditional NSAIDs (tNSAIDs) that
inhibit both COX-1 and COX-2, and COX-2 selective NSAIDs, colloquially
termed coxibs. However, several older NSAIDs (e.g., diclofenac, meloxicam,
nimesulide) exert some degree of COX-2 selectivity similar to the first coxib—
celecoxib. Therefore these drugs are sometimes more accurately termed as
COX-2 selective NSAIDs, although this has not been used commonly (Grosser
et al., 2011; Rang et al., 2015b).
NSAIDs could also be classified on basis of their pharmacokinetic proper-
ties, that is, plasma t (Section 1.1.2).
1/2
Paracetamol (acetaminophen) is conventionally separated from the NSAID
group and classified as a nonopioid analgesic or analgesic–antipyretic. It shares
many properties with tNSAIDs relevant to its clinical action (e.g., analgesic and
antipyretic action) but it has some important differences. It is largely devoid of
anti-inflammatory activity, and its mechanism of action appears to be only part-
ly related to COX-inhibition (Borazan and Furst, 2015; Grosser et al., 2011).
1.1.1.2 COX Isoforms and Their Roles
COX-1 and COX-2 are closely related (they share >60% sequence identity) and
catalyze the same reaction—the formation of prostaglandins (PG)s PGG and
2
PGH from arachidonic acid (Fig. 1.1). Arachidonic acid is released from mem-
2
brane phospholipids by phospholipase A , which is activated by various stimuli
2
(inflammatory, physical, chemical, and mitogenic). PGG and PGH are cyclic
2 2
endoperoxides, unstable intermediates that are converted by tissue (relatively)
specific enzymes to PGs (PGE , PGF , PGD , and PGI ), and to thrombox-
2 2α 2 2
ane A (TxA ) collectively named prostanoids (FitzGerald and Patrono, 2001;
2 2
Smyth et al., 2011). Tissue specificity is illustrated by the examples of TxA ,
2
that is the dominant COX-1 product in platelets, and PGE , that is the dominant
2
COX-2 product in macrophages (Smyth et al., 2011).
The expression of COX-1 and COX-2 and their roles in the body are mostly
different (Grosser et al., 2011; Rang et al., 2015b; Smyth et al., 2009).
COX-1 is a predominantly constitutive enzyme widely expressed in most
tissues including gastrointestinal (GI) mucosa, platelets, endothelium, kidneys,
and uterus (Frölich, 1997; Jouzeau et al., 1997; Smyth et al., 2011). It has a