Preface
Page: i-i (1)
Author: Martin Masuelli and Mauricio Filippa
DOI: 10.2174/9789815049428123010001
Physical Pharmacy
Page: 1-28 (28)
Author: Mauricio Filippa*
DOI: 10.2174/9789815049428123010003
PDF Price: $15
Abstract
In this chapter, we focus on solutions. In the introduction, general and
descriptive aspects are defined, such as the classification of solutions and the addition
of solids. Considering the properties of these systems, we focus on definitions related
to colligative properties, and on the use of this property for the adjustment of isotonic
solutions considering the selective capacity of the membranes, differentiation of
tonicity and osmolarity. We also introduce the calculations necessary for the
preparation of isotonic solutions with blood plasma, using the mass and volume
adjustment method. The solutions require different methods of expressing their
concentration, and in order to develop this point, we present the different forms of
expression, with extensive detail on one of the variables, i.e., normality, very important
in the formulation of parenteral solutions. Since the preparation of solutions is an
important aspect, we detail the existing interactions between the solute and the solvent,
specify the thermodynamic aspects that condition the solubility of the solute in the
solvent, and develop variables such as polar interactions, capacities to accept or give
Hydrogen bridge junctions and the energy requirement to generate space within the
solvent, giving a rational look at the process of improving the capacity of the solvent to
contain the solute. The dissolution rate is another variable developed through simple
equations, which make an analysis of the factors that modify it, such as agitation,
temperature, particle size, and diffusion coefficient. We also describe variables such as
the pH and the dielectric constant of the solvent to modify solubility.
Preformulation: Active Pharmaceutical Ingredient-Excipient Compatibility Studies
Page: 29-44 (16)
Author: Adriana Segall*
DOI: 10.2174/9789815049428123010004
PDF Price: $15
Abstract
A relevant area of research in the preformulation phase for the development
of new dosages is active pharmaceutical ingredient (API)-excipient compatibility. The
possibilities of chemical and physical interaction of API and the excipients may affect
how efficient and effective it is, while displaying an impact on the nature, stability and
availability of API. The most common signs of deterioration of an API are changes in
the color, taste, odor, polymorphic form, or crystallization (pharmaceutical
incompatibility). These changes arise from chemical reactions with the excipient,
leading to degradation of the API. The active components are usually more stable than
solid dosage forms, and although testing the compatibility of API-excipients is
essential, no protocol has yet been accepted to evaluate their interactions. Fourier
Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC),
Isothermal Stress Testing-High Performance Liquid Chromatography (IST-HPLC), Hot
Stage Microscopy (HSM), Scanning Electron Microscopy (SEM), Solid state Nuclear
Magnetic Resonance Spectroscopy (ssNMR) and Power X-ray Diffraction (PXRD) are
commonly used as screening techniques for assessing the compatibility of an active
pharmaceutical ingredient (API) with some currently employed excipients. The
potential physical and chemical interactions between drugs and excipients can affect
the chemical nature, the stability and bioavailability of drugs and, consequently, their
therapeutic efficacy and safety. Once the solid-state reactions of a pharmaceutical
system are understood, the necessary steps can be taken to avoid reactivity and improve
the stability of drug substances and products. In this chapter, we summarize the
techniques to investigate the compatibility between APIs and excipients.
Some Medicinal Chemistry Applications of the QSAR/QSPR Theory
Page: 45-61 (17)
Author: Pablo R. Duchowicz* and Juan C. Garro-Martínez
DOI: 10.2174/9789815049428123010005
PDF Price: $15
Abstract
The application of QSAR/QSPR techniques and computer-aided modelling
are considered valuable tools to initiate the search for new drugs, and nowadays, these
are being intensively used for this purpose. Trustworthy models can provide insight
into the structural characteristics that may influence the drug inhibitory activity,
drastically improving the success and the pace of the development of more effective
drugs with weaker secondary effects. The present book chapter revises and comments
on different recent QSAR/QSPR applications conducted in medicinal chemistry field in
the last five years (2016-2020), developed on various interesting biological activities
and physicochemical properties of drug compounds.
Computer-assisted Study of Garlic Organosulfur as Antioxidant Agents
Page: 62-82 (21)
Author: Mario G. Díaz, Esteban G. Vega-Hissi, Matias F. Andrada and Juan C. Garro Martinez*
DOI: 10.2174/9789815049428123010006
PDF Price: $15
Abstract
Although many sulfur-containing garlic compounds exhibit antioxidant
activity, little is known about the molecular mechanisms through which these
compounds react with reactive oxygen species. For this reason, in this chapter, we
present a summary of various papers in which, the scavenging of hydrogen peroxide
and hydroxyl radical by garlic compounds allyl methyl disulfide, allyl methyl sulfide,
and diallyl sulfide is analyzed from a theoretical-quantum outlook.
Different computational methods and methodologies were analyzed. The DFT
functional B3LYP, CAM-B3LYP, BKM, M05-2X, and M06-2X and even other
methods such as Gaussian-n (G3MP2B3) were also evaluated. A broad series of basis
sets were used from the simple 6-31G(d) to the extended triple-zeta 6-311++G(3df,2p).
The thermodynamic and kinetic aspects of different proposed reactions were explored.
Epoxidation, sulfonation, and hydrogenation were some of the processes raised as
possible reaction pathways. Reaction mechanisms were proposed for each pathway,
and different methods used to obtain the TS structure (TS Berny, QST2, and QST3)
were compared. The kinetic and the rate constants were obtained through the Intrinsic
Reaction Coordinate calculations. Gas and aqueous phases were mostly utilized in our
papers; however, we included and studied the behavior of the systems in non-polar
environments in our last publication.
Enzymes in Biocatalysis: Characteristics, Kinetic Approach, Production, and Uses
Page: 83-107 (25)
Author: Lucrecia L. Chaillou, Valeria Boeris, Darío Spelzini and Mónica A. Nazareno*
DOI: 10.2174/9789815049428123010007
PDF Price: $15
Abstract
Enzymes are proteins that efficiently catalyze chemical reactions of specific
substrates; they are highly specific for one reaction or a class of reactions, based on the
structure of their active sites. This chapter presents the classification according to the
nature of the reactions where enzymes are involved as biocatalysts and shows examples
of biocatalyzed chemical processes. Kinetic aspects are discussed, and the relevance of
the kinetic parameters is highlighted. Inhibitors of enzyme-mediated reactions are also
described and classified; their kinetic implications are revealed; besides, examples of
enzyme inhibition, examples of pharmacological drug-inhibition are presented. The
roles of enzyme cofactors and cosubstrates are described taking examples of biological
systems. Enzymes are also used in bioremediation processes and examples are
mentioned. Enzyme production strategies developed to enable industrial application are
presented, taking lactase as a model example; enzyme preparation, purification,
recovery, and stabilization are the key steps in their utilization. Nowadays, with the
development of genomics and proteomics, it is possible to access new enzyme
activities as well as manipulate, design and improve new and traditional enzyme
activities. Biocatalysis is a multidisciplinary area of science that is gaining increasing
interest both from a scientific point of view and for its growing industrial applications
due to its high specificity in the conversion of substrates into specific products, the
reduced volume of waste generated and the non-aggressive operating conditions.
Specifically, the enzymes’ use in pharmacological drugs synthesis is remarkably
interesting, since they allow to improve both the performance and the stereoselectivity
of the active principles.
Antifungal Agents
Page: 108-134 (27)
Author: Estefanía Butassi, Laura Svetaz and Maximiliano Sortino*
DOI: 10.2174/9789815049428123010008
PDF Price: $15
Abstract
Fungal infections represent an increasing threat to a growing number of
immune- and medically compromised patients. Fungi, like humans, are eukaryotic
organisms and there are a limited number of selective targets that can be exploited for
antifungal drug development. This has also resulted in a very restricted number of
antifungal drugs that are clinically available for the treatment of superficial and
invasive fungal infections at the present time. Moreover, the utility of available
antifungals is limited by toxicity, drug interactions and the emergence of resistance,
which contribute to high morbidity and mortality rates. These limitations have created a
demand for the development of new antifungals, particularly those with novel
mechanisms of action.
The 1990s can be considered the “golden era” of antifungal drug development with
multiple big pharmaceutical companies actively engaged in the discovery and
development of novel antifungals. However, this has largely become stagnant since
then, and it has been two decades since the newest class of antifungal agents (the
echinocandins) reached the market. Overall, there are currently few classes of FDA-approved antifungal agents clinically used in the treatment of fungal infections. In this
chapter, we reviewed antifungal drugs and summarized their mechanisms of action,
pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics
inhibit nucleic acid and microtubule synthesis, membrane ergosterol synthesis and cell
wall polymers’ synthesis, or sequestrate ergosterol. The experimental antifungal drugs
in clinical trials are also reviewed. We report sphingolipids and protein biosynthesis
inhibitors, which represent the most promising emerging antifungal therapies.
Naturally and Chemically Sulfated Polysaccharides in Drug Delivery Systems
Page: 135-196 (62)
Author: Héctor J. Prado*, María C. Matulewicz and Marina Ciancia
DOI: 10.2174/9789815049428123010009
PDF Price: $15
Abstract
Sulfated polysaccharides have always attracted much attention in food,
cosmetic and pharmaceutical industries. These polysaccharides can be obtained from
natural sources such as seaweeds (agarans, carrageenans, fucoidans, mannans and
ulvans), or animal tissues (glucosaminoglycans). In the last few years, several neutral
or cationic polysaccharides have been sulfated by chemical methods and anionic or
amphoteric derivatives were obtained, respectively, for drug delivery and other
biomedical applications. An important characteristic of sulfated polysaccharides in this
field is that they can associate with cationic drugs generating polyelectrolyte-drug
complexes, or with cationic polymers to form interpolyelectrolyte complexes, with
hydrogel properties that expand even more their applications. The aims of this chapter
are to present the structural characteristics of these polysaccharides, to describe the
methods of sulfation applied and to review extensively and discuss developments in
their use or their role in interpolyelectrolyte complexes in drug delivery platforms. A
variety of pharmaceutical dosage forms which were developed and administered by
multiple routes (oral, transdermal, ophthalmic, and pulmonary, among others) to treat
diverse pathologies were considered. Different IPECs were formed employing these sulfated polysaccharides as the anionic component. The most widely investigated is κ-carrageenan. Chitosan is usually employed as a cationic polyelectrolyte, with a variety
of sulfated polysaccharides, besides the applications of chemically sulfated chitosan.
Although chemical sulfation is often carried out in neutral polysaccharides and, to a
less extent, in cationic ones, examples of oversulfation of naturally sulfated fucoidan
have been found which improve its drug binding capacity and biological properties.
Immunomodulatory Plant Extracts and their Compounds. Evaluation of your Safety
Page: 197-224 (28)
Author: Roberto C. Davicino* and Claudia Anesini
DOI: 10.2174/9789815049428123010010
PDF Price: $15
Abstract
Medicinal herbs have been in use for the management of human health, for
prevention. as well as for the cure of human diseases since ancient civilizations. In
recent times, the use of herbal drugs has increased in both developed and developing
countries, because of the large chemical, pharmacological, and clinical knowledge of
plant drugs and their derivatives, the development of new analytical methods for
quality control, the development of new forms of preparation and administration of
plant drugs and their derivatives and finally the relatively wide therapeutic margins
with less frequent adverse effects. However, naturals are not a synonym for innocuous
as many adverse effects can occur. In this regard, there are different levels of
perceptions about the safety of medicinal herbs, varying from “completely safe” to
“completely harmful”, although there is also a clear idea about its side effects
depending on factors such as dosage, characteristics of the plant material and
consumer-related factors. Because of this, medicinal plants need to be studied and
effective and innocuous doses must be established.
Nowadays, immunomodulatory drugs have gained a main role principally as a
consequence of COVID-19 produced by the SARS-CoV-2 virus.
Some South American plants frequently used in Argentine folk medicine such as
Larrea divaricata and Ilex paraguariensis and others used all over the world like Tilia
spp. and Coffeea Arabica are known to exert immune-enhancing effects.
In this review, we discussed some reports about the immunological effect of the
mentioned plants and their majority compounds, focusing on their efficacy and safety.
Biofilms: the Achilles’ Heel of Antimicrobial Resistance
Page: 225-241 (17)
Author: María Gabriela Paraje*
DOI: 10.2174/9789815049428123010011
PDF Price: $15
Abstract
Microbial biofilms are communities of sessile cells with a three-dimensional
(3D) extracellular polymeric substance (EPS). The EPS consists of exopolysaccharides,
nucleic acids (eDNA and eRNA), proteins, lipids, and other biomolecules, that they
produce and are irreversibly attached to living or non-living surfaces. This is the most
frequent growth mode of microorganisms in nature. The biofilm formation consists of
several steps, starting with attachment to a surface and the formation of microcolonies.
Subsequently, in the maturation step, three-dimensional structures are formed and end
the life cycle of biofilms with the dispersal or detachment of the cells. This type of
growth has been reported to be more resistant to antimicrobial treatment and immune
response than its planktonic (free-living) counterparts. Several intrinsic resistance
factors including the interaction between antimicrobial and biofilm matrix components,
reduced growth rates, persister cells presence, increased production of oxidative stress,
and antagonist and degradation mechanisms may be active in some parts of the
biofilms have been described. Extrinsic factors such as increased horizontal genes
transmission conferring antimicrobial resistance have been described contributing to
the biofilm antimicrobial resistance.
Due to the heterogeneous nature of biofilms, it is likely that multiple mechanisms of
biofilm antimicrobial resistance are useful in order to explain biofilm survival in a
number of cases, being the result of an intricate mixture of intrinsic and extrinsic
factors. The understanding of the nature of biofilm development and drug tolerance are
great challenges for the use of conventional antimicrobial agents and indicate the need
for multi-targeted or combinatorial therapies.
Development of Analytical Methods for Analysis of Drugs of Abuse in Biological Fluids using Design of Experiments and Response Surface Methodology
Page: 242-276 (35)
Author: Christiano dos Santos, Caroline Fernandes Grecco, Jacques Florêncio and Delia Rita Tapia Blácido*
DOI: 10.2174/9789815049428123010012
PDF Price: $15
Abstract
New Psychoactive Substances (NPS), also known as design drugs, are
developed by modification of the chemical structure of the initially prohibited
substances. The idea behind this strategy is to create alternatives for consumption and
to evade national and international control measures applied to controlled substances,
bypassing the legislative prohibition. In this context, the emergence of NPS has raised
questions about the analytical methods that can be applied to identify and to
characterize these substances in different scenarios, including biological fluids
(serum/plasma, whole blood, oral fluid, and urine). Because biological fluids are
complex matrixes, a sample preparation step is required to remove undesired
endogenous matrix components and to isolate and pre-concentrate the analytes before
chromatographic analysis. Different extraction or sample preparation techniques such
as liquid-liquid extraction, solid phase extraction, dispersive liquid-liquid
microextraction, and microextraction by packed sorbent can be used prior to
chromatographic analysis (gas chromatography, mass spectrometry, or liquid
chromatography mass spectrometry). All these techniques involve many factors that
must be optimized so that the analytical method can detect NPS in biological samples.
Tools like design of experiments (DoE) and Response Surface Methodology (RSM)
can contribute to the study and optimization of the variables involved in these
analytical techniques. This book chapter shows how experimental design tools (full
factorial design, fractional factorial design, Plackett-Burman design, Box-Behnken
design, central composite design) and response surface methodology can aid the
development of analytical methods for the analysis of drugs of abuse in biological
fluids.
Steric Exclusion Chromatography (including the Chromatography of Polymers in an Aqueous Solution)
Page: 277-298 (22)
Author: Marguerite Rinaudo*
DOI: 10.2174/9789815049428123010013
PDF Price: $15
Abstract
This chapter describes the different difficulties encountered when studying a
new polymer by GPC or SEC. This technique is known as liquid chromatography in
which a soluble polymer is eluted through a porous gel filling a column. The different
molecular weights are separated following their hydrodynamic volumes compared with
the pore diameters. It appeared in the sixties firstly in an aqueous medium. The main
factors playing a role in the elution through the porous support are examined.
Especially, the SEC behaviour of water-soluble polymers is discussed introducing the
behaviour in aqueous medium where H bonds and hydrophobic interactions are
important. Examples of dextrans and neutral oligosaccharides, rich in -OH groups are
discussed showing that weak adsorption increases the elution volumes when eluted in
water. Other important interactions concern the electrostatic interactions causing
exclusion from the gels and changes in the polyelectrolyte conformation. Elution with
monovalent electrolytes (NaNO3
or NaOAc) around 0.1M is recommended. SEC of
charged oligosaccharides, hyaluronan, pectins and chitosan are briefly described.
Fortunately, new equipment appeared progressively and especially in 1983 the
multiangle laser light scattering (MALLS) was introduced, which is probably the most
useful detector to associate with the differential refractometer. In that case, Mw is
obtained independently of the elution volume as soon as there are no aggregates and
good solubility of the polymer tested in the solvent selected. To conclude, it is
necessary to insist on the quality of the polymeric solution avoiding the presence of
aggregates which may be identified by dynamic light scattering (DLS). In their
presence, even after filtration on 0.2 µm pore membrane, the SLS overestimates the
Mw.
Intrinsic Viscosity Methods in Natural Polymer as Pharmaceutical Excipients
Page: 299-329 (31)
Author: Federico Becerra, Lismet Lazo Delgado, Maria F. Garro, Jesica Gassmann, Franco Tonelli, Liliana Villegas, Sergio Picco, Monica Aubert, Mario E. Aguilera Merlo and Martin Masuelli*
DOI: 10.2174/9789815049428123010014
PDF Price: $15
Abstract
Intrinsic viscosity is the most economical and used measure in the
determination of polymers and biopolymers used as excipients in the pharmaceutical
industry. The most used methods in the measurement of intrinsic viscosity are Huggins,
Kraemer, Schulze-Blashke and Martin, the first being used as a standard and reference
for the others. There are also Simple Point methods such as Solomon Ciuta and others
that help in this regard. In this chapter, we will focus on those methods best known and
applied in intrinsic viscosity measurements. In the measurement of intrinsic viscosity in
dilute solutions of polymers, experimental methods such as Huggins, Martin, Kraemer
and Shulze-Blashke are particularly useful. In dilute concentrations, graphical methods
such as those of Fuoss, Fidors, and Tanglertpaibul and Rao can also be used without
major errors. Although there are many more methods these can be more difficult and
impractical in their calculations and graphs. The methods furthest from experimental
practicality are those that depend on other methods and constants, such as Budtov's and
Baker´s. As for the simple point methods, the simplest and most used is that of
Solomon-Ciuta, the rest have similar or better results. As for the proposed methods, the
most prominent and with the least error is Square, the rest being affordable but with a
somewhat higher margin of error
Extraction Techniques in Green Analytical Chemistry
Page: 330-364 (35)
Author: Andres Fabián Pighin, Laura Natalia Rigacci, Emiliano Camilli, Ana Clara Chirillano, Juan Ángel Cufré and María Emilia Villanueva*
DOI: 10.2174/9789815049428123010015
PDF Price: $15
Abstract
Analytical chemistry determinations are not exempted from generating
environmental contamination. A variety of strategies are now being proposed to reduce
the impact on the environment caused by the different stages of the analytical process.
These strategies can focus on the different stages of the analysis, ranging from sample
collection and preparation to the acquisition and processing of analytical signals.
Sample preparation constitutes a basic and crucial stage in the success of any analytical
method and extraction is one of the most chosen techniques. Extractions often involve
the use of a large amount of harmful solvents that may damage the health of the
operator and the environment, into which these solvents are disposed of, often without
treatment. Therefore, new techniques have been applied in order to reduce the impact
of this procedure, also focusing on lowering the costs and complexity, always taking
into account the quality of the procedures. Current trends in green analytical chemistry
are directed towards simplification, miniaturization, and automation, also involving the
use of solvent-free, environmentally friendly procedures and, at the same time,
maintaining acceptable extraction efficiencies in a short time.
In this chapter, the fundamentals and technological advances in green extraction
systems will be presented. Through representative examples of different compounds in
different matrices, the advantages and limitations of different procedures will be
presented, including ultrasound-assisted extraction, pressurized solvent extraction,
microwave-assisted extraction, single drop liquid-liquid extraction, headspace
extraction, dispersive liquid-liquid microextraction, hollow-fiber liquid-phase
microextraction, micro-solid phase extraction, stir-bar sorptive extraction and stir-cake
sorptive extraction
Subject Index
Page: 365-370 (6)
Author: Martin Masuelli and Mauricio Filippa
DOI: 10.2174/9789815049428123010016
Introduction
Advanced Pharmacy is a textbook dedicated to advanced applications in pharmacy. The book balances information by including chapters that give basic knowledge and inform readers on the latest insights in pharmaceutical science. Authored by pharmacology experts and academics, each chapter highlights current knowledge in the field, presenting research in a didactic and educational manner for academics, researchers, and students who need to understand pharmacy. Additional features of the book include chapter summaries and references for advanced readers. Topics: Physical Pharmacy: Covers foundations of physical pharmacy, providing a solid understanding of the subject. Preformulation Studies: examines active pharmaceutical ingredient-excipent compatibility studies, a crucial aspect of drug formulation. Medicinal Chemistry Applications: explores medicinal chemistry applications using QSAR/QSPR theory. Computer-assisted Study: explains computer-assisted studies with the example of garlic organosulfur as an antioxidant agent. Enzymes in Biocatalysis: sheds light on enzyme characteristics, kinetics, production, and applications in biocatalysis. Antifungal Agents: provides insights into antifungal agents and their significance. Polysaccharides in Drug Delivery: explores the use of naturally and chemically sulfated polysaccharides in drug delivery systems. Immunomodulatory Plant Extracts: covers the evaluation of safety and benefits of immunomodulatory plant extracts. Biofilms and Persistent Cells: examines the development, causes, and consequences of biofilms and persistent cells. Analytical Methods for Drug Analysis: focuses on the development of analytical methods for analyzing drugs of abuse using experimental design. Steric Exclusion Chromatography: discusses steric exclusion chromatography, including chromatography of polymers in aqueous solutions. Intrinsic Viscosity Methods: explores intrinsic viscosity methods in natural polymer pharmaceutical excipients. Extraction Techniques in Green Analytical Chemistry: highlight environment-firendly techniques in analytical chemistry. Advanced Pharmacy is a comprehensive resource that bridges the gap between pharmaceutical research and practice, offering invaluable insights into the latest developments in the field. This textbook serves as an essential reference for both learners and scholars in basic and advanced courses in pharmacy and pharmaceutical science.