Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5626_Библиотеки_им_академика_М_И_Перельмана.pdf
References 271
8. Formation of Fatty Acyl CoA
3 Singh, V., Singh, A.K., Bhargava, P. (Eds.). et al. (2020).
Engineering of Microbial Biosynthetic Pathways.
4 Walsh, C.T. and Tang, Y. (2017). Natural Product
Biosynthesis. Royal Society of Chemistry.
5 Peck, S.C. and van der Donk, W.A. (2013). Phosphonate
6 Ghosh, S., Chisti, Y. and Banerjee, U.C. (2012).
7 Santos-Sánchez, N.F., Salas-Coronado, R., Hernández-
Aspects of Phenolic Compounds 1: 1–15.
8 Conn, E.E. (Ed.). (2013). The Shikimic Acid Pathway
9 Talapatra, S.K. and Talapatra, B. (2015). Shikimic acid
Stereochemistry, Conformation, Synthesis, Biology, and
Medicine, 625–678. Heidelberg: Springer.
10 Starcevic, A., Akthar, S., Dunlap, W.C. et al. (2008).
References
1 Evans, W.C. (2009). Trease and Evans’ Pharmacognosy.
Academy of Sciences 105 (7): 2533–37.
11 Fernandez, M. and Zuniga, M. (2006). Amino acid
Reviews in Microbiology 32 (3): 155–83.
12 Wendisch, V.F. (Ed.). (2007). Amino Acid Biosynthesis–
Pathways, Regulation and Metabolic Engineering (Vol. 5).
13 Meijer, A.J. (2003). Amino acids as regulators and
of Nutrition 133 (6): 2057S–62S.
14 Rohmer, M. (1999). The Discovery of a Mevalonate-
Reports 16 (5): 565–74.
15 Dubey, V.S., Bhalla, R. and Luthra, R. (2003). An
Biosciences 28: 637–46.
16 Lichtenthaler, H.K., Schwender, J., Disch, A. et al.
17 Khare, S., Singh, N.B., Singh, A. et al. (2020). Plant
2 Michal, G. (1999). Biochemical Pathways (Vol. 46).
Biology 63: 203–16.
18 Harwood, C.R., Mouillon, J.M., Pohl, S. et al. (2018).
23 Drew, S.W. and Demain, A.L. (1977). Effect of primary
Microbiology 31 (1): 343–56.
24 Sanchez, S. and Demain, A.L. (2008). Metabolic
19 Dixon, M. and Webb, E.C. (1960). Enzymes. Academic
20 Kraut, J. (1988). How do enzymes work? Science
21 Boyer, P.D. and Krebs, E.G. (1986). The Enzymes.
22 Copeland, R.A. (2023). Enzymes: A Practical
Introduction to Structure, Mechanism, and Data
Analysis. John Wiley & Sons.
Microbial Biotechnology 1 (4): 283–19.
25 Erb, M. and Kliebenstein, D.J. (2020). Plant secondary
Physiology 184 (1): 39–2.
14
Pharmaceutical Aids of Natural Origin
Santosh Yele1, Ashwini Deshpande2, Kanchan Salgar2, Mohan Kalaskar
1
Department of Pharmacognosy, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, India
2
SVKM’s NMIMS School of Pharmacy & Technology Management, Green Industrial Park, Polepally SEZ, TSIIC, Hyderabad, Telangana
3
Department of Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India
3
14.1 Introduction
Paracelsus, a fifteenth-century scholar, postulated that
every drug exhibits adverse effects when administered in
sufficiently high doses. The selection of synthetic pharmaceuticals for formulations is often driven by the prevalence
of mild-to-moderate side effects. Adverse effects of these
pharmaceuticals may manifest as direct toxicity, immunotoxicity, allergy, or intolerance. Although occurrences of
these effects are infrequent, the escalating utilization of
these products has raised concerns since the commencement of the twentieth century [1]. In addition to environmental concerns, there is a growing market for green
products in several industries, such as food, cosmetics, and
pharmaceuticals [2, 3]. This inclination motivates the quest
for innovative substitutes to formulate products that are
not only safer but also environmentally conscious. Within
this framework, the pharmaceutical sector is progressively
focusing on the characteristics of pharmaceutical aids.
Historically, pharmaceutical aids are inactive components
essential for ensuring active pharmaceutical ingredients’
(APIs) appropriate quality, safety, and effectiveness. APIs
can be derived from various sources, including biological,
mineral, plant-based, and chemical synthesis-based
sources [4]. However, the International Pharmaceutical
Excipients Councils (IPEC) provide a more comprehensive
and sufficient definition of excipients, defining them as
any material (apart from the API) that has undergone
safety testing and is approved for use in pharmaceutical
dosage forms [5]. According to definitions, a pharmaceutical excipient is a substance or a blend of substances that
occupies a defined volume when combined, serving as a
carrier while incorporating APIs within a mixture [6].
Pharmaceutical excipients serve a multitude of functions, encompassing tasks such as occupying the formulation volume, ensuring the stability of the API, improving
precision and accuracy in API dosing, enhancing bioavailability, and facilitating API administration by refining
organoleptic features or manufacturing a more aesthetically pleasing final pharmaceutical form. Additionally,
they contribute to enhancing patient acceptance of the
treatment. It is critical to emphasize that the safety and
efficacy of excipients are closely tied to these aforementioned functions. The paramount role of any excipient is to
guarantee the medicine’s safety and effectiveness throughout the formulation, storage, and administration phases.
Assessing the toxicological properties of pharmaceutical
aids, whether inherent or specific, presents a nuanced
challenge owing to the wide array of excipients featuring
diverse chemical compositions, origins, and technological
roles. Additionally, the potential existence or emergence
of by-products and impurities further complicates this
matter [7, 8].
Since the inception of medication production, pharmaceutical aids have been referred to as inactive compounds
added to the API just to get the desired consistency in the
formulation. Excipients are now recognized as more than
just inert substances, as they have the potential to interact
274 14 Pharmaceutical Aids of Natural Origin
Pharmaceutical
Aids of Natural
origin
Sources
Plant
Animal
Marine
Mineral
Microorganism
Figure 14.1 Classification of Natural Pharmaceutical aids. Source: Santosh U Yele.
with the API, thereby decreasing its potency. Additionally,
these excipients may introduce unwanted impurities or
Chemical nature
Aqueous,
Alcoholic
Acidic, Ether,
ester,
Carbohydrates,
Tannins, Protiens
Glycosides, Salts
of minerals
Natural pharmaceutical aids derived from plant sources
offer several advantages in pharmaceutical formulations.
impact the processes of absorption, distribution, metabolism, and excretion (ADME), consequently diminishing
the overall bioavailability of the API. It is acknowledged
that excipients play functional and vital roles in contemporary pharmaceutical formulations. Despite their importance, a universally accepted and consistent global standard
for ensuring the safety of excipients within the pharmaceutical industry is still lacking. Therefore, several natural
ingredients were employed in the formulation of medications due to their safety profile and compatibility [9, 10].
Advancements in pharmaceutical technology have enabled the evaluation of excipients right from their source,
allowing for the assessment of their interactions within a
mixture of other excipients and APIs. This process provides
a means to monitor and understand their performance.
Consequently, this capability leads to the development of
formulations that have the potential to enhance the bioavailability and effectiveness of the API as needed.
1. Natural origin: herbal pharmaceutical aids are
sourced from plants, providing a natural and sustainable option for pharmaceutical formulations.
2. Biodegradability: these pharmaceutical aids are
often biodegradable, contributing to environmentally
friendly and sustainable drug development.
3. Low toxicity: herbal pharmaceutical aids exhibit
lower toxicity than their synthetic counterparts,
enhancing their safety profile in pharmaceutical
applications.
4. Compatibility: they are generally compatible with a
wide range of APIs, allowing for versatile use in different drug formulations.
5. Cost-effectiveness: herbal pharmaceutical aids can
be cost-effective due to their widespread availability
and ease of extraction, potentially reducing production
costs.
Use/application
Disintegrants,
Diluents, suspending
agents
Binders, lubricants,
glidants
Colors, Plastsizers,
Coating agents
Surfactants,
Preservatives
14.2 Some Industrially Important Pharmaceutical Aids 275
6. Pharmacological benefits: some herbal pharmaceu-
tical aids may possess inherent pharmacological properties, providing additional therapeutic benefits in
addition to their role as formulation components.
7. Patient acceptance: using herbal ingredients aligns
with the increasing preference for natural and plantbased products, improving patient acceptance.
8. Regulatory compliance: herbal pharmaceutical aids
may comply with regulatory requirements for natural
and organic ingredients, facilitating regulatory approval
processes.
9. Enhanced stability: certain herbal pharmaceutical
aids contribute to the stability of formulations, potentially extending the shelf life of pharmaceutical
products.
10. Cultural significance: in regions with a rich history
of traditional medicine, incorporating herbal pharmaceutical aids may align with cultural practices, promoting acceptance and integration into healthcare
systems. [11–13]
While herbal excipients offer several advantages in pharmaceutical formulations, it is important to acknowledge
certain disadvantages associated with their use. Firstly,
variability in the composition of herbal materials may lead
to inconsistent performance and efficacy in drug formulations. The extraction process of herbal excipients can be
complex and may result in batch-to-batch variations,
impacting the reproducibility of formulations. Moreover,
allergens in herbal excipients can pose a risk to individuals
with sensitivities or allergies. Herbal materials may also
exhibit inherent batch-specific impurities, raising concerns
about product safety. Certain herbs’ limited availability and
cultivation challenges can lead to supply chain issues and
increased production costs. Additionally, the potential for
interactions between herbal excipients and certain drugs
needs careful consideration to avoid adverse effects.
Standardization of herbal extracts can be challenging due
to the diverse chemical profiles of plant materials. The
taste and odor of herbal excipients may affect the overall
acceptability of the drug formulation. Lastly, the lack of
comprehensive regulatory guidelines for herbal excipients
may result in uncertainties regarding their quality, purity,
and compliance with pharmaceutical standards [14, 15].
14.2 Some Industrially Important Pharmaceutical Aids
14.2.1 Acacia Gum
Acacia gum, also known as Gum Arabic, is derived from
plants, such as Acacia nilotica, Acacia seyal, and Acacia
senegal, all of which belong to the Leguminosae family.
This substance falls under the polysaccharide category of
biopolymers [16]. It is a biocompatible and bio-degradable
gummy polysaccharide. Gum acacia is a mildly acidic heteropolysaccharide. Acacia is a bit acidic heteropolysaccharide. Acacia possesses various functional physical
properties, including great swelling capacity, pH stability,
water solubility, and exceptional ability to produce gel [17].
Gum acacia available as salts of various metals potassium,
calcium, and magnesium of polysaccharides acids with
side chains of D-glucopyranosyl, L-rhamnopyranosyl,
L-arabinofuranosyl, and D-glucopyranosyl uronic acid
units and a main chain of (1, 3)-β-D-galactopyranosyl units
[18–20] (Figure 14.2). For numerous years, gum Arabic has
been utilized as a stabilizing agent, thickening agent, emulsifier, suspending agent, and more in a multitude of food
products and cosmetics. It is a firmly established excipient
for tablet formulations [21–25].
14.2.2 Agar-agar
Agar-agar, often known as agar, is a gelatinous biopolymer
formed from red algae, namely the Rhodophyta phyllum.
The composition of agar-agar includes galactose and
3,6-anhydrogalactose, which form a polymeric structure
H
C
O
HOOC
H
H H
HO
HO
HO
H
CH2OH
HO
H
HO
H
H
2
O
HO
HO HO
H H
H
H
O
H
O D
H
HO
O
HO
Figure 14.2 Chemical structure of Acacia gum.
H
O
- Galp
HOOC
H
HO
HO
H
C
O
2
O
HO
OCH
H
HO
H
HO
H
H
H
H
2
HO
HO
H
O
H
O D
H
H
H
H
HOOC
H
O
HHO
O
- Galp
HO
H
H
HO
H
OCH
HO
H
HO
H
H
HO
H2C
O
O
HO
H
H
H
2
O
H
HO
H
H
H
O D
HO
H
O
HHO
O
- Galp
276 14 Pharmaceutical Aids of Natural Origin
CH2OH
OH
O
β
Figure 14.3 Main chemical components of agar-agar.
OH
Agarose
O
O
α
O
CH
OH
2
O
(Figure 14.3). Furthermore, the agar-agar molecular structure contains an inorganic sulfate chemically bound to the
carbohydrate. The composition consists of two constituents, namely agarose and agaropectin [26]. One type of linear polysaccharide is agarose.
Agaropectin is a mixture of smaller molecules. An
increase in temperature causes agar-agar to become more
soluble in water. Agar-agar is commonly used in various
applications, such as nutrient and non-nutrient agar.
Specifically in microbiology, it is used in the form of
growth media like sabouraud agar (for fungi), blood agar,
pharmaceutical agar, chocolate agar, selective neomycinblood agar, trypticase or tryptone soy agar, etc. [27].
Pharmaceutical agar finds extensive application in the
formulation and development of tablets, granules, and
novel drug delivery systems (NDDS), such as microparticles and nanoparticles. Its widespread use is attributed to
its ready accessibility, cost-effectiveness, capacity for
cold-setting, non-toxic nature, and biodegradability.
Agar-agar has recently been utilized to develop hydrogels
to regulate medication release [28].
14.2.3 Albumin
Another significant naturally occurring protein polymer is
albumin, the most abundant blood protein. It is a reservoir
and moves many materials, including metals, nutrients,
pollutants, and hormones. Hepatocytes in the liver are the
primary source of albumin production. There are three
distinct forms of albumin, namely ovalbumin, human
serum albumin, and bovine serum albumin [29].
Ovalbumin, a monomeric phosphoglycoprotein, is a
highly useful ingredient in food and medicine products
because of its affordable, easily accessible, emulsion-stabilizing, and pH- and temperature-responsive properties
[30]. Bovine serum albumin’s remarkable ligand binding
characteristic makes it popular for drug delivery applications. Similarly, due to its widespread presence as a hydrophilic plasma protein and its biodegradability, human
serum albumin has emerged as a pivotal component in
numerous drug delivery systems [31, 32]. Recent advancements have seen the development of albumins tailored for
nanoparticle formation, further expanding their utility in
various drug delivery applications [33–40].
CH
OH
2
OH
O
β
Figure 14.4 The molecular composition of the sodium salt of
alginic acid.
OH
Agaropectin
H
O
O
-
COO
O
H
OH OH
H H
OH
OH
CH
OSO
2
3
O
O
H H
O
α
H
H
OH
COONa
H
O
O
n
14.2.4 Alginates
Alginate biopolymers are derived from marine algae, specifically brown sea algae like Laminaria hyperborea,
Macrocystis pyrifera, and Ascophyllum nodosum [41]. These
biopolymers consist of salts of alginic acid (Figure 14.4),
natural polysaccharides commercially harvested from
marine sources. The molecular structure of alginate
includes linear blocks with (1 4)-linkages connecting β-Dmannuronic acid (M unit) and α-L-guluronic acid (G unit)
monomers [42]. Alginate molecules create negatively
charged copolymers with different ratios of G-G, M-G, and
M-M units, arranged asymmetrically and linked by 1,4-glycosidic bonds (Figure 14.4). In their original form, alginates are salts combined with various metal cations present
+
in seawater, including sodium (Na
barium (Ba
2+
), strontium (Sr2+), and others [43]. Sodium
), magnesium (Mg2+),
alginate, the sodium derivative of alginic acid (Figure 14.3),
is a primary ingredient in pharmaceutical manufacturing.
It exhibits ionotropic gelation, a process activated by diva-
2+
lent or trivalent metal cations, such as Ca
2+
Pb
, Zn2+, Cd2+, Al3+, and Fe3+ [44–46]. Ionotropic gela-
, Ba2+, Cu2+,
tion occurs due to cross-linking interactions between monovalent sodium ions and cross-linking di-/tri-valent metal
cations, forming an “egg-box” structure by stacking guluronic groups in the alginate structure. This results in junction zones where metal cations cross-link the ions, binding
the polysaccharides [47, 48].
The interaction between di-/tri-valent metal cations and
monovalent sodium ions within sodium alginate molecules
leads to the attraction of polymer chains to each other. This
attraction is due to intimate contacts between ionotropic
cross-linking di-/tri-valent metal ions and carboxylate ions
14.2 Some Industrially Important Pharmaceutical Aids 277
of sodium alginate molecules, which occur within the
spaces between two polyuronate chains. These metal ions
are effectively coordinated by other electronegative oxygen
atoms [42]. Alginates are extensively employed in pharmaceutical formulation, including emulsions, gels, capsules,
tablets, buccal patches, and various particulates like beads,
microparticles, and nanoparticles. This widespread application is attributed to their advantageous physico-chemical
properties, encompassing solubility, viscosity, cross-linking, and the ability to transform sol-gel. They exhibit desirable biological properties, including immunogenicity,
biocompatibility, and bio-adhesion. Researchers are developing customized alginate materials for enhanced, intelligent drug delivery systems [49–52].
14.2.5 Anthocyanidins
Anthocyanidin is a vivid flavonoid that exhibits a spectrum of hues. The glycoside form of anthocyanidins,
anthocyanin, is found in plants much more often than its
parent compound, anthocyanidin. These water-soluble
plant pigments, known as anthocyanins, are responsible
for the coloration of terrestrial products, including fruits,
vegetables, and leaves, whenever their inherent color
manifests [53, 54]. The nomenclature of anthocyanins is
derived from the Greek words “antho” and “cyanidin,” signifying flower and dark blue, respectively. The catalog
comprises over 540 known natural shades of anthocyanins, making them one of the largest groups of easily
extractable water-soluble plant pigments. The substantial
diversity is emphasized by identifying more than 700 distinct patterns [55]. Six principal aglycone anthocyanidins
– namely, cyanidin, delphinidin, petunidin, peonidin, pelargonidin, and malvidin – are ubiquitously distributed
and significant in the human diet [56]. These aglycones
inherently consist of sugars and can undergo additional
acylation through interaction with aromatic or aliphatic
acids (Figure 14.5). Both acylation and glycosylation processes enhance the structural robustness of anthocyanin,
mirroring the natural occurrences. Certain fruits exhibit a
sole type of anthocyanin, such as cyanidin in apples, cherries, and figs, while others, like cherries and cranberries,
showcase a combination of cyanidin and peonidin, yielding a spectrum of colors, such as red, purple, blue, and
yellow, as observed in grapes, raspberries, or strawberries
[53, 57].
Beyond beverages, anthocyanin finds utility in coloring
various non-beverage food products, including gelatin, candies, fruit fillings, and specific confectioneries. The application of anthocyanins as natural pigments has faced challenges
due to unfavorable stability. When the hydroxyl group predominates, the color tends to shift toward a blue hue, while
the dominance of the methoxy group results in a reddish tint
[56]. Various factors, such as pH, temperature, light, copigment presence, protein, oxygen, and sugars, significantly
influence the stability of anthocyanin pigments [58].
14.2.6 Cellulose
Cellulose is a prominent homopolysaccharide that naturally exists as the primary structural element within plant
cell walls. Its origins lie in diverse renewable sources, predominantly found in plant fibers (such as cotton, hemp,
linen, jute, and wood fibers) [59]. Moreover, several microorganisms can make cellulose. A polymer of anhydro-βglucose, it comprises β (1, 4) glycosidic connection between
D-(+)-β-glucose. Crystalline microfibrils are partly formed
by their many parallel cellulose molecules and linear,
unbranched polysaccharide chains (Figure 14.6) [60, 61].
Due to their high mechanical strength, resistance to enzymatic assaults, and alignment, these crystalline cellulose
microfibrils are crucial in providing structural support to
both plant and bacterial cell walls [62].
Powdered cellulose can be obtained through the mechanical disintegration of cellulose derived from fibrous materials,
such as cotton and wood. Powdered cellulose has demonstrated its efficacy as a filler in the formulation of medicinal
tablets. High-quality powdered cellulose is generated through
chemical treatment with HCl, resulting in microcrystalline
cellulose. This form is preferred above regular powdered cellulose due to its excellent flowability and non-fibrous particle
structure. It is also utilized as a diluent and binder in medicinal tablets, utilizing direct compression and granulation
techniques. Cellulose exhibits low biodegradability in living
R
1
OH
+
O
OGlu
OH
Figure 14.5 Basic structure of anthocyanin.
OH
R
CH2OH
O
O
2
OH
H
Figure 14.6 Chemical structure of cellulose.
CH
OH
2
O
O
H
O
OH
n
278 14 Pharmaceutical Aids of Natural Origin
organisms, although its higher-order structure can be altered
to make it susceptible to hydrolysis [63]. The exceptional ability of this substance to be transformed into a wide range of
derivatives renders it a prime candidate as a raw material for
many biomedical uses. Diverse techniques, such as esterification, carboxymethylation, graft copolymerization, and crosslinking reactions can generate distinct cellulose derivatives
with varied properties and functionalities. The functionalization of cellulose produces various cellulose derivatives
through chemical modifications, such as hydroxypropyl
methylcellulose (HPMC) and carboxymethyl cellulose
(CMC). Additionally, cellulose can be esterified to yield valuable semi-synthetic products, such as cellulose nitrate, cellulose acetate, and cellulose acetate phthalate, among others.
Cellulose derivatives are employed to prepare various membrane-controlled drug release formulations, including developing enteric coatings for tablets and granules and creating
semi-permeable membranes utilized in osmotic pumps
[60–62, 64, 65].
14.2.7 Chitosan
Chitosan is a biopolymer obtained from marine sources,
specifically generated from chitin by a process called deacetylation reaction. Chitin is derived from the exoskeletons
of crustaceans or the cell walls of fungi. This marine-origin
biopolymer, known as chitin, is utilized as a foundational
substance for the production of chitosan. Chitosan molecules are composed of an amino polysaccharide structure
consisting of α-1, 4-linked 2-amino-2-deoxy-α-D-glucose
(N-acetyl glucosamine) (Figure 14.7).
The key determinant for the solubility of chitosan in
water resides in unbound amino groups and N-acetyl
groups within its molecular structure [32, 66, 67].
Chitosan is a cationic polymer possessing unbound
amino groups and exhibits insolubility in water under
neutral or alkaline pH conditions. Chitosan molecules
become soluble in water when the amino groups within
them undergo protonation in an acidic environment with
a lower pH. Chitosan, a biopolysaccharide with a cationic character and several free amino groups, can
undergo cross-linking [68–73]. In recent decades, chitosan has found application as a material for drug carriers
in various pharmaceutical dosage forms, facilitating the
delivery of a diverse range of medications. This is
attributed to its commendable biocompatibility and biodegradability properties.
Nevertheless, the extensive utilization of chitosan as a
potential biopolymeric component in drug delivery systems encounters limitations owing to its swift degradation
or dissolution within the acidic milieu of the stomach. This
impedes the controlled release of drugs from oral drug
delivery systems incorporating chitosan. Researchers
actively developed and utilized chemically modified chitosan materials to address this drawback and establish controlled drug-release carrier systems [74–86].
14.2.8 Cochineal
Red insect pigments result from the extraction of carminic
acid (from cochineal), lactic acid (Lac dye), kermesic acid
(Kermes), and Tyrian purple from dried insects and mollusks. In ancient times, these substances were widely
employed for pigment production [87]. The cochineal bug,
abundant in South Africa, is the key source of red pigments. Carminic acid (Figure 14.8), the primary anthraquinone colorant, is soluble in water. Its color shifts from
falling acidity red to violet [88]. These insects heavily rely
on color additives for their food and beverages, making carmine a prominent choice in this industry.
Crude extracts from oranges containing carminic acid
undergo a purification process before incorporation into
color formulations. The widely used carmine pigment is
synthesized using cochineal extract with aluminum sulfate under acidic conditions. This chemical reaction forms
a complex between the metal and carminic acid, causing a
shift in the absorption peak and creating an insoluble red
lake during sol-gel polymerization. Subsequent processing
steps produce water-dispersible powders, and the introduction of calcium ions can aid in lake precipitation.
Carminic acid and its derivatives have diverse applications
in various food products, such as ice cream, candy, desserts, beverages, and dairy items [89]. In the animal kingdom, tetrapyrroles like biliverdin contribute to the
development of blue pigments. Armenian cochineal, an
ancient crimson pigment utilized in the Middle East and
CH2OH
H
OH
H
O
H
NH
H
2
H
Figure 14.7 Chemical structure of chitosan.
CH2OH
H
H
O
OH
H
O
H
NH
OH
O
HO
HO
O
OH
OH
OH
O
O
H
n
2
HO
Figure 14.8 Chemical structure of carminic acid.
CH
OH
OH
O
3
14.2 Some Industrially Important Pharmaceutical Aids 279
Europe since 714 BC, imparts vibrant hues to silk and
wool garments, transforming them into intricately dyed
masterpieces [90, 91].
14.2.9 Curcumin
Curcumin is isolated from the rhizomes of the Curcuma
longa Linn, commonly identified as the curcuma plant.
Chemically, it is recognized as diferuloylmethane. The
structure is characterized by two hydrophobic aromatic
rings linked by a seven-carbon system containing an α,βunsaturated β-diketone moiety (Figure 14.9). Renowned
for its vibrant yellow hue, curcumin finds significant applications in the food and cosmetic industries due to its insolubility in water and polar solvents like chloroform,
dimethyl sulfoxide (DMSO), ethanol, acetonitrile, and
ethyl acetate. It is only sparingly soluble in hexane and
cyclohexane. Curcumin is recognized therapeutically for
its multifaceted properties, including antiparasitic, antiinflammatory, antispasmodic, antimicrobial, antioxidant,
and anticancer effects. The skincare industry also values
curcumin for its attributes as an antioxidant, antiseptic,
anti-inflammatory, and anti-aging agent. The skincare
industry also explores it for antioxidant, antiseptic, antiinflammatory, and anti-aging attributes [96–99].
14.2.10 Gelatin
Gelatin represents a naturally derived protein biopolymer
with inherent biodegradability and versatility. Its distinctive feature lies in its thermo-reversible characteristics.
O
OH
HO
OCH
3
Figure 14.9 Structure of curcumin.
H3CO
OH
This composite comprises proteins and peptides resulting
from the partial hydrolysis of collagen from animal bones
and skin trimmings. [100, 101] Gelatin is known for its
high glycine, proline, and hydroxyproline concentrations
in its polymeric chain form. Gelatin is classified into two
categories, type A and type B, based on the hydrolysis
method it undergoes. Type A gelatin refers to gelatin that
has been hydrolyzed under acidic conditions, while type B
gelatin is produced through hydrolysis under primary conditions. Because gelatin is thermo-reversible, it is considered a unique biopolymer with the sol-gel transformation
feature. It has been frequently employed as an emulsifier,
thickener, and stabilizer. It is a constituent ingredient in
the pharmaceutical industry that formulates soft and hard
gelatin capsules. Thanks to its significant swelling property, gelatin’s capacity to produce hydrogels has made it a
valuable element for drug delivery applications. In addition to these characteristics, gelatin can generate films.
This technique has already been utilized to create microparticles and nanoparticles for delivering a wide range of
substances, such as medicines, proteins, enzymes, DNA,
and more [64, 71, 100, 102–105].
14.2.11 Gellan Gum
Gellan gum, a biopolymer, is synthesized via microbial fermentation involving the microorganism Pseudomonas elodea. Two
chemically distinct variants of gellan gum exist: the deacetylated
form, characterized by a reduced number of acyl groups, and
another form, known as the native form, which is distinguished
by a higher number of acyl groups. Both variants share a typical
linear tetrasaccharide structure, consisting of(1→4)-L-rhamnose-α
(1→3)-D-glucose-β-(1→4)-D-glucuronic acid-β-(1→4)-D-glucose
as the repeating sugar units (Figure 14.10) [106–109]. The difference in substitutions between the two forms of gellan gum
introduces a potential variation in the gelling properties of this
substance.
Gellan gum is a biopolymeric pharmaceutical excipient
across various drug delivery formats, such as tablets, gels,
hydrogels, beads, microparticles, nanoparticles, and films.
OH
O
HO
OH
O
Figure 14.10 Chemical structure of gellan gum.
OH
O
H
HO
O
OH
H
O
OH
H
O
O
HO
OH
O
HO
H
O
OH
n
280 14 Pharmaceutical Aids of Natural Origin
Recent research has emphasized the advancement of ionotropically gelled gellan gum beads, which involves the utilization of deacetylated gellan gum in the ionotropic
cross-linking gelation process facilitated by di- or trivalent
metal cations. Scientific literature has extensively documented this approach [110–114].
14.2.12 Guar Gum
Guar gum represents a non-ionic polysaccharide plantbased polymer derived from Cyamopsis tetragonoloba
seeds, a Leguminosae family member. Guar gum’s key features and advantages include its physicochemical stability,
ability to dissolve in water, high capacity for swelling, ability to biodegrade, and compatibility with living organisms.
Additionally, its unique gelling network structure has led
to its utilization in formulating various controlled-release
oral dosage forms, including tablets, beads, microparticles,
pellets, etc. [115–119]. Additionally, its unique gelling network structure has led to its utilization in formulating various controlled-release oral dosage forms, including tablets,
beads, microparticles, pellets, etc. Researchers have
recently synthesized modified guar gum versions with
physical and chemical properties. These modified derivatives are designed to regulate the significant expansion of
native guar gum in various pH environments. These derivatives have been utilized in the development of drug delivery systems with improved properties [120, 121]. Guar gum
is recognized for its susceptibility to enzymatic degradation
by colonic microorganisms. This particular characteristic
has positioned guar gum as a favored option for the formulation of orally administered drug delivery systems specifically designed to target the colon [122–128].
with significant therapeutic value [129]. Sterculia gum is
derived from the exudates of the Sterculia urens plant, which
belongs to the Sterculiaceae family [130, 131]. Sterculia gum
is produced by extracting exudates from the tree bark of
S. urens through peeling or cutting. The exudates play a
crucial role as the unrefined source material in the production of sterculia gum. The lipopolysaccharide, slightly acetylated, is comprised of three distinct chains. The primary
chain constitutes approximately 50% of the overall polysaccharide, featuring repetitive units of four galacturonic acid
residues. L-rhamnose residues are situated at the reducing
end, accompanied by a β-D-galactose branch. The second
chain, accounting for about 17% of the polysaccharide, is
characterized by recurring units composed of L-rhamnose
residues at the reducing end, four galacturonic acid residues,
and a β-D-galactose branch. Approximately 17% of the polysaccharide comprises the second chain of sterculia gum
molecules with oligorhamnan, which includes branches of
D-galacturonic acid and residues of D-galactose. Around
30% of polysaccharides comprise the third chain of sterculia
gum molecules. The chain consists of D-glucuronic acid
residues, including galactose, rhamnose, and uronic acid
residues [131–134]. Sterculia gum possesses several notable
characteristics, including high viscosity, exceptional resistance to acidity, strong swelling ability, biodegradability, biocompatibility, nonallergenic qualities, and non-teratogenic
properties. Sterculia gum exhibits antibacterial properties as
well. In recent times, sterculia gum has gained significant
traction as an indispensable pharmaceutical excipient, finding extensive utilization across various applications, including tablet formulations, microparticles, beads, hydrogels,
and mucoadhesive drug delivery systems [135–139].
14.2.13 Gum Karaya
Karaya gum is an alternative name for sterculia gum. The
water-soluble polysaccharide is a plant-derived compound
CH2OH
O
H
H
O
CH
2
OH
H
H
OH
H
Figure 14.11 Chemical structure of guar gum.
O
OH
H
H
OH
H
H
OH
H
CH
2
H
H
OH
O
H
14.2.14 Gum Tragacanth
Gum tragacanth is a natural polysaccharide formed from different species of the Astragalus genus, namely from A. gum-
mier, A. tragacanth, and A. microcephalus Willd. These plants
OH
CH
2
O
OH
O
OH
H
H
H
O
CH
OH
2
H
H
H
OH
O
H
O
OH
H
H
OH
H
H
OH
H
O