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 Encyclopedia of Biomedical Polymers and Polymeric
Biomaterials

ISSN: (Print) (Online) Journal homepage: http://www.tandfonline.com/doi/book/10.1081/E-EBPP

Pharmaceutical Polymers

Narendra Pal Singh Chauhan , Arpit Kumar Pathak , Kumudini Bhanat ,

Rakshit Ameta , Manish Kumar Rawal , Pinki B. Punjabi

To cite this entry: Narendra Pal Singh Chauhan , Arpit Kumar Pathak , Kumudini Bhanat ,
Rakshit Ameta , Manish Kumar Rawal , Pinki B. Punjabi . Pharmaceutical Polymers. In
Encyclopedia of Biomedical Polymers and Polymeric Biomaterials. Taylor and Francis: New
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 Pharmaceutical Polymers

Narendra Pal Singh Chauhan

Department of Polymer Science, University College of Science, Mohanlal Sukhadia University, Udaipur, India
Arpit Kumar Pathak
Kumudini Bhanat
Department of Chemistry, University College of Science, Mohanlal Sukhadia University, Udaipur, India
Rakshit Ameta
Department of Chemistry, Pacific College of Basic and Applied Sciences, Pacific Academy of Higher Education and Research
Society (PAHER) University,, Udaipur, India
Manish Kumar Rawal
Department of Chemistry, Vidya Bhawan Rural Institute, Udaipur, India
Pinki B. Punjabi
Department of Chemistry, University College of Science, Mohanlal Sukhadia University, Udaipur, India
Downloaded by [Narendra P. S. Chauhan] at 00:27 14 April 2016

Abstract
Synthetic and natural-based polymers have found their way into the pharmaceutical and biomedical industries,
and their applications are growing at a fast pace. Major applications of polymers in the current pharmaceutical
field are for controlled drug release, which will be discussed in detail in the following sections. In the
biomedical area, polymers are generally used as implants and are expected to perform long-term service.
In general, the desirable polymer properties in pharmaceutical applications are film forming (coating),
thickening (rheology modifier), gelling (controlled release), adhesion (binding), pH-dependent solubility
(controlled release), solubility in organic solvents (taste masking), and barrier properties (protection and
packaging). From the solubility point of view, pharmaceutical polymers can be classified as water-soluble
and water-insoluble (oil soluble or organic soluble). In this entry, many water-soluble biomedical and
pharmaceutical polymers including polyethylene glycol (PEG), polyvinyl alcohol, polyethylene oxide,
polyvinyl pyrrolidone, polyacrylate or polymethacrylate esters, cellulose-based polymers, hydrocolloids,
and many plastics and rubbers will be tabulated and their anionic and cationic functionalities will be
summarized and discussed. This entry will also focus on PEGylation, defined as the covalent attachment of
PEG chains to bioactive substances.

INTRODUCTION Examples of pharmaceutical polymers:

Synthetic and natural-based polymers have found their 1. Vinyl polymers

way into the pharmaceutical and biomedical industries 2. Cellulose ethers
and their applications are growing at a fast pace. The use 3. Polyesters
of polymers for biomedical and pharmaceutical applica- 4. Silicones
tions has gained an enormous impact during the past 5. Polysaccharides and related polymers
6. Miscellaneous polymers
decades. Polymers can be applied in drug delivery
systems, as scaffolds for tissue engineering and repair,
and as novel biomaterials.[1] Polymers are becoming APPLICATION OF BIOMEDICAL
increasingly important in the field of drug delivery. The PHARMACEUTICAL POLYMERS
pharmaceutical applications of polymers range from their
use as binders in tablets to viscosity and flow controlling In a traditional pharmaceutics area, such as tablet manufac-
Pharmaceutical—Plant Oil

agents in liquids, suspensions, and emulsions. Polymers turing, polymers are used as tablet binders to bind the
can be used as film coatings to disguise the unpleasant excipients of the tablet. Advanced pharmaceutical dosage
taste of a drug, to enhance drug stability, and to modify forms utilize polymers for drug protection, taste masking,
drug release characteristics. controlled release of a given drug, targeted delivery,

Encyclopedia of Biomedical Polymers and Polymeric Biomaterials DOI: 10.1081/E-EBPP-120050558

Copyright © 2015 by Taylor & Francis. All rights reserved. 5929
 5930 Pharmaceutical Polymers

increase drug bioavailability, and so on and so forth. To one
side from solid dosage forms, polymers have found appli-
cation in liquid dosage forms as rheology modifiers.
They are used to control the viscosity of an aqueous solu-
tion or to stabilize suspensions or even for the granulation
step in preparation of solid dosage forms. Major applica-
tions of polymers in the current pharmaceutical field are for
controlled drug release, in the biomedical area. Polymers
are generally used as implants and are expected to perform
long-term service. This requires that the polymers have
unique properties that are not offered by polymers intended
for general applications. Table 1 provides a list of polymers
with their applications in pharmaceutical and biomedical
industries. In general, the desirable polymer properties in
pharmaceutical applications are film forming (coating),
thickening (rheology modifier), gelling (controlled release),
adhesion (binding), pH-dependent solubility (controlled
release), solubility in organic solvents (taste masking), and
barrier properties (protection and packaging). From the
solubility standpoint, pharmaceutical polymers can be

Table 1 Polymers in pharmaceutical and biomedical applications

Name of the Polymer Applications
Water-Soluble Synthetic Polymer
Poly(ethylene oxide) Coagulant, flocculent, swelling agent
Poly(vinyl pyrrolidone) Plasma replacement, tablet granulation
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Poly(vinyl alcohol) Water-soluble packaging, tablet binder, tablet coating

Poly(ethylene glycol) Plasticizer, base for suppositories
Poly(isopropyl acrylamide) and poly(cyclopropyl methacrylamide) Thermogelling acrylamide derivatives, its balance of
hydrogen bonding, and hydrophobic association changes
with temperature
Water-Insoluble Biodegradable Polymers
(Lactide-co-glycolide) polymers For protein delivery
Starch-Based Polymer
Sodium starch glycolate Superdisintegrant for tablets and capsules in oral delivery
Starch Glidant, a diluent in tablets and capsules, a disintegrant in
tablets and capsules, a tablet binder
Plastics and Rubbers
Polycyanoacrylate Biodegradable tissue adhesives in surgery, a drug carrier in
nano- and microparticles
Polychloroprene Septum for injection, plungers for syringes, and valve
components
Polyisobutylene Pressure-sensitive adhesives for transdermal delivery
Silicones Pacifier, therapeutic devices, implants, medical grade adhesive
for transdermal delivery
Polystyrene Petri dishes and containers for cell culture
Poly(methyl methacrylate) Hard contact lenses
Poly(hydroxyethyl methacrylate) Soft contact lenses
Poly(vinyl chloride) Blood bag, hoses, and tubing
Hydrocolloids
Carrageenan Modified release, viscosifier
Chitosan Cosmetics and controlled drug delivery applications,
mucoadhesive dosage forms, rapid release dosage forms
Pectinic acid Drug delivery
Alginic acid Oral and topical pharmaceutical products; thickening and
Pharmaceutical—Plant Oil

suspending agent in a variety of pastes, creams, and gels, as

well as a stabilizing agent for oil-in-water emulsions; binder
and disintegrant
Cellulose-Based Polymers
Hydroxypropyl methyl cellulose Binder for tablet matrix and tablet coating, gelatin alternative
as capsule material
Hydroxyethyl and hydroxypropyl cellulose Soluble in water and in alcohol, tablet coating
 Pharmaceutical Polymers
classified as water-soluble and water-insoluble (oil soluble
or organic soluble). The cellulose ethers with methyl and
hydroxypropyl substitutions are water-soluble, whereas
ethyl cellulose and a group of cellulose esters such as cel-
lulose acetate butyrate or phthalate are organic soluble.
Hydrocolloid gums are also used when solubility in water is
desirable. The synthetic water-soluble polymers have also
found extensive applications in pharmaceutical industries,
among them polyethylene glycol (PEG), vinyl alcohol poly-
mers, polyethylene oxide (PEO), polyvinyl pyrrolidone, and
polyacrylate or polymethacrylate esters containing anionic
and cationic functionalities are well established (Table 1).
CLASSIFICATION OF BIOMEDICAL
PHARMACEUTICAL POLYMERS
Polymers have played important roles in the preparation of
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biomedical pharmaceutical products. Their applications
range widely from material packaging to fabrication of the
most sophisticated drug delivery devices. Of the many
materials used in the pharmaceutical formulations, poly-
mers play the most important roles. The use of polymers
ranges from the manufacturing of various drug packaging
materials to the development of dosage forms.
Polymers in pharmaceutical applications are classified
into three general categories according to their common uses:
1. Polymers in conventional dosage forms
2. Polymers in controlled release dosage forms
3. Polymers for drug packaging
From the solubility point of view, pharmaceutical poly-
mers can be classified into two categories:
1. Water-soluble polymers
2. Water-insoluble polymers (oil soluble or organic
soluble)
Polymers in Conventional Dosage Forms
Despite the well-known advantages of controlled release
dosage forms, conventional dosage forms are still more
widely used, probably because they cost less to manufac-
ture. More than three-quarters of all drug formulations are
made for oral administration. Oral dosage forms such as
tablets, capsules, and liquids are still most popular. Since
tablet is one of the most widely used dosage forms and its
preparation requires the incorporation of polymers, we will
focus on polymers used in the tableting process.
Polymers Used in Controlled Release Dosage
Forms
One of the most important applications of polymers in
modern pharmaceutics is the development of new, advanced
drug delivery systems, commonly known as controlled
5931
release drug delivery systems. Controlled release formula-
tions attempt to alter drug absorption and subsequent drug
concentration in blood by modifying the drug release rate
from the device. Polymer use in controlled release dosage
is reduced fluctuations in the plasma drug concentration,
less side effects, and increased patient compliance. Con-
trolled release products consist of the active agent and the
polymer matrix or membranes that regulate its release.
Advances in controlled release technology in recent years
have been possible as a result of advances in polymer sci-
ence that allow the fabrication of polymers with tailor-
made specifications, charge density, such as molecular
size, specific functional groups, hydrophobicity, biocom-
patibility, and degradability. Controlled release dosage
forms refresh old drugs by reducing pharmaceutical short-
comings and improving biopharmaceutical properties of
the drugs. Polymers used in controlled release dosage
forms are an alternative to the development of new drugs,
which is extremely costly. The controlled release dosage
forms are also important in the delivery of newly devel-
oped protein drugs. Currently, most protein drugs are
administered by injection. Although protein drugs have
delicate bioactivity, its success in treating chronic illness
largely depends on the development of new delivery sys-
tems for the routine administration other than injection.
The mechanisms of controlled drug delivery can be
classified into the following five mechanisms: 1) diffusion;
2) dissolution; 3) osmosis; 4) ion-exchange; and 5) poly-
meric prodrug. In all cases, polymers function as a princi-
pal component that controls the transport of drug molecules
and the way this process is utilized in the device determines
the primary mechanism for each drug delivery system.
Polymers for Drug Packaging
Many polymers are used as packaging materials for phar-
maceutical products. The properties of the plastic packag-
ing materials, such as gas permeability, flexibility, and
transparency, are responsible for specific applications.
Flexible packages are made by the use of thin and flexible
polymer films. When they are wrapped around a product,
they can easily adapt their shape to conform to the shape of
the contents. The thin, flexible films are usually produced
from cellulose derivatives, Ppoly(vinyl chloride) (PVC),
polyethylene, polypropylene, polyamide (nylon), polysty-
rene, polyesters, polycarbonate, poly(vinylidene chloride),
and polyurethanes. These polymeric materials are gener-
ally heat sealable and are also capable of being laminated
to other materials.[2] A tight package can be prepared by
Pharmaceutical—Plant Oil
wrapping an article with these polymer films followed by a
brief heat treatment. Rigid packages such as bottles, boxes,
trays, cups, vials, and various closures are made from
materials of sufficient strength and inflexibility. Widely
used polymers are high-density polyethylene, polypropyl-
ene, polybutene, poly(vinyl chloride), acrylic copolymers,
polycarbonate, nylon, and polyethylene terephthalate (PET).
 5932
Biodegradable PET is preferred due to environmental con-
cerns, but it is expensive.
The closing or cap of the container is typically made of
polypropylene or polyethylene. The cap is usually lined with
moisture-resistant materials such as low-density polyethyl-
ene, polyvinyl chloride, or poly(vinylidene dichloride).[3]
Polyisoprene, ethylene propylene/dicylopentadiene copoly-
mer, styrene/butadiene copolymer, polybutadiene, silicone
elastomers, and natural rubber are used as polymeric ingre-
dients of the rubber stopper.[4] One of the most important
necessities of any packaging material is that it should not
release any component into the drug product. The prepara-
tion of containers free from any leachable components are
especially important for the containers of ophthalmics, par-
enteral products, and any liquid products. It was shown that
di(2-ethylhexyl) phthalate was released from the PVC bags
and that caused uncertainty of the taxol solution.[5] United
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States Pharmacopeia/NF offers the protocol of chemical,
spectral, and water vapor access tests and tolerances for plas-
tic containers.[6] Among those, a chemical test is designed to
give a quantitative assessment of the extractable materials in
both organic solvents and water. When drugs are stored in
the polymeric containers or in contact with polymer sur-
faces, the drug loss by adsorption to the polymer surface
should be considered. It was reported that significant por-
tions (ranging from 23% to 55%) of drugs, such as diaze-
pam, isosorbide dinitrate, nitroglycerin, and warfarin
sodium, were lost during the 24 hr storage in PVC bags.[7]
Caution should be exercised in the use of polymeric contain-
ers and other devices for the delivery of protein drugs, since
proteins readily adsorb and sometimes denature on the
hydrophobic polymer surface. It was shown that more than
90% of tissue necrosis factor was lost when delivered using
a burette mixing set simply due to the adsorption onto the
surface of the delivery device.[8] It has been projected that
insulin molecules aggregate in the bulk solution as a result
of adsorption to the container surface and subsequent dena-
turation.[9] Clearly, the loss of protein drugs by adsorption to
the polymeric surface can be significant.[10,11]
Taste Masking
Taste is an important factor in the development of dosage
form. Taste masking becomes a requirement for bitter
drugs to improve patient agreement especially in the
pediatric and old population. Taste-masking technologies
are increasingly paying attention on aggressively bitter
tasting drugs like the macrolide antibiotics, non-steroidal
anti-inflammatory drugs, and penicillin. Taste-masking
Pharmaceutical—Plant Oil
technologies offer a great scope for invention and patents
(Fig. 1). Undesirable taste is one of the significant formu-
lation problems encountered with most drugs. The meth-
ods most commonly involved for achieving taste masking
include various chemical and physical methods that pre-
vent the drug substance from interaction with taste buds.
The simplest method for taste masking is to use of flavor
Pharmaceutical Polymers
Fig. 1 Taste masking.
enhancers. Where these methods fail, more complex
methodologies are adopted. A variety of techniques have
been recognized for taste masking, which include poly-
mer coating, inclusion complex formation with cyclo-
dextrin, use of ion exchange resins, solubility-limiting
methods, liposome, multiple emulsions, use of anesthetic
agents, etc.
Methods usually in use for achieving effective taste
masking include various physical and chemical methods
that prevent the drug substance from interaction with the
taste buds:
1. Use of flavor enhancers.
2. Applying polymer coatings: Polymer coating is one of
the most important methods of taste masking of bitter
drugs. It avoids direct contact of the bitter drug with the
taste buds. The selection of polymer for taste masking
is based on the physiochemical property and compati-
bility with the drug.[12,13] A water-soluble polymer such
as a cellulose acetate, cellulose butyrate, hydroxyethyl
cellulose is used in taste masking of bitter drug.
3. Complexation with ion exchange resins.
4. Inclusion complex formation with cyclodextrins.
Rheology Modifiers
Rheology modifiers commonly referred to as thickeners or
viscosifiers are ever present in most of the products. The
use of these additives cut across several process industries
including food, pharmaceuticals, cosmetics and personal
care, adhesives, textile, ceramics, paper, detergents, paints,
inks, and coatings, among others. Rheology can be defined
as “the science or study of how things flow.” Thickeners
come from both natural and synthetic sources. Naturally
occurring polymers comprise polysaccharide or amino
acid building blocks and are generally water-soluble. Com-
mon examples are starch, cellulose, alginate, egg yolk,
agar, arrowroot, carrageenan, collagen, gelatin, guar gum,
pectin, and xanthan gum.
 Pharmaceutical Polymers
Barrier Properties
Barrier polymers are used for many packaging and protec-
tive applications. As barriers, it is a separate system, such
as an article of food or an electronic component, from an
environment. Barrier polymers’ boundary movement of
substances is called permeants. The movement can be
through the polymer or, in some cases, merely into the
polymer. After crossing the barrier polymer, the permeant
moves to the polymer surface, desorbs, and moves away.
Permeant movement is a physical process that has both a
thermodynamic and a kinetic component. For polymers
without special surface treatments, the thermodynamic
contribution is in the solution step. The permeant partitions
between the environment and the polymer are generally
according to thermodynamic rules of solution. The poly-
mers that are good barriers to permanent gases, especially
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oxygen, have important commercial significance. Vinyli-
dene chloride copolymers are available as resins for extru-
sion, latices for coating, and resins for solvent coating.
Hydrolyzed ethylene–vinyl acetate copolymers, com-
monly known as ethylene–vinyl alcohol (EVOH) copoly-
mers, are usually used as extrusion resins, although some
may be used in solvent-coating applications. Copolymers
of acrylonitrile are used in extrusion and molding appli-
cations. Commercially important comonomers for barrier
applications include styrene and methyl acrylate. Poly-
amide polymers can provide a good-to-moderate barrier-
to-permeation by permanent gases. Two often-used
polymers have adequate properties for some applications.
Poly(ethylene terephthalate) is used to make films and
bottles. PVC is a moderate barrier-to-permanent gas.
Plasticized PVC is used as a household wrapping film. In
regard to water–vapor transmission rate (WVTR) values,
those polymers that are good oxygen barriers are often
poor water–vapor barriers and vice versa. Polymer mole-
cules without dipole–dipole interactions, such as polyole-
fins, dissolve very little water and have low WVTR and
permeability values. The permeation of flavor, aroma, and
solvent molecules in polymers follow the same physics as
the permeation of small molecules, but with two signifi-
cant differences. For these larger molecules, the diffusion
coefficients are much lower and the solubility coefficients
are much higher. Furthermore, the large solubility coeffi-
cient can lead to enough sorption of the large molecule so
that plasticization occurs in the polymer, which can
increase the diffusion coefficient. Generally, vinylidene
chloride copolymers and glassy polymers such as poly-
amides and EVOH are good barriers to flavor and aroma
permeation, whereas polyolefins are poor barriers. Sev-
eral physical factors can affect the barrier properties of a
polymer. These include temperature, humidity, orienta-
tion, and cross-linking. Typically, the permeability
increases 5–10% for every increase of 1°C. When a poly-
mer equilibrates with a humid environment, it absorbs
water. This can plasticize the polymer and increase the
5933
permeability. The effect of orientation on the permeability
of polymers is difficult to assess; diffusion in some poly-
mers is unaffected by orientation, and in others increases
or decreases are observed. Cross-linking has been shown
in few cases to decrease the diffusion coefficient. Reason-
able prediction can be made of the permeabilities of low
molecular weight gases such as oxygen, nitrogen, and
carbon dioxide in many polymers. The diffusion coeffi-
cients are not complicated by the shape of the permeant,
and the solubility coefficients of each of these molecules
do not vary from polymer to polymer.
Gelling
Gels are semisolid vehicles for drug. The gel has been used
as a medium for the delivery of drug for both local treat-
ment and systematic effect. Gel remains one of the most
popular and important pharmaceutical dosage forms.
There are many types of gelling agents used in pharmaceu-
tical applications. There are some common gelling agents
are acacia, alginic acid, bentonite, Carbopols (now known
as carbomers), carboxymethylcellulose, ethylcellulose
(EC), gelatin, hydroxyethylcellulose, hydroxypropyl cel-
lulose, magnesium aluminum silicate, methylcellulose
(MC), poloxamers, polyvinyl alcohol (PVA), sodium algi-
nate, and xanthan gum. Topical gel formulations of diclof-
enac sodium were prepared by using Carbopol 934,
Carbopol 940, sodium carboxymethylcellulose (NaCMC),
and polymer as a gel-forming material that is biocompati-
ble and biodegradable. The transdermal and topical deliv-
ery of drugs afford advantages over conventional oral
administration. Hydroxypropyl methylcellulose (HPMC)
is one of the most commonly used hydrophilic biodegrad-
able polymers for developing controlled release formula-
tions, because it works as a pH-independent gelling agent.
HPMC is a widely accepted pharmaceutical excipient
polymer, because HPMC is available in a wide range of
molecular weights and the successful control of gel viscos-
ity is easily possible.[14] The development of in situ gel sys-
tems has received significant attention over the past few
years. In situ gel forming drug delivery systems are in prin-
ciple capable of releasing drugs in a sustained manner
maintaining relatively constant plasma profiles. Both natu-
ral and synthetic polymers can be used for the production
of in situ gels. In situ gelling systems are liquid at room
temperature but undergo gelation when in contact with
body fluids or change in pH. The formation of gel depends
on factors like temperature modulation, pH change, pres-
Pharmaceutical—Plant Oil
ence of ions, and ultra violet irradiation from which the
drug gets released in a sustained and controlled manner. In
situ gelling systems are liquid at room temperature but
undergo gelation when in contact with body fluids or
change in pH. Carboxymethyl mungbean starch (CMMS)
is also investigated as a gelling agent in the topical
pharmaceutical.[15]
 5934
POLYETHYLENE GLYCOL
PEG is a polyether compound with many applications from
industrial manufacturing to medicine. PEG is also known
as PEO or polyoxyethylene (POE), depending on its
molecular weight. PEGs contain potential toxic impurities,
such as ethylene oxide and 1,4-dioxane. PEGs are nephro-
toxic if applied to damaged skin.[16]
They are used commercially in numerous applications,
including as surfactants, in foods, in cosmetics, in pharma-
ceutics, in biomedicine, as dispersing agents, as solvents,
in suppository bases, as tablet excipients, and as laxatives.
Some specific groups are lauromacrogols, nonoxynols,
octoxynols, poloxamers, macrogol used as a laxative, is a
form of PEG. PEG is the basis of a number of laxatives
(e.g., macrogol-containing products, such as Movicol and
PEG 3350, or SoftLax, MiraLAX, or GlycoLax). Whole
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bowel irrigation with PEG and added electrolytes is used
for bowel preparation before surgery or colonoscopy. PEG
is used as an incipient in many pharmaceutical products.
Lower-molecular-weight variants are used as solvents in
oral liquids and soft capsules, whereas solid variants are
used as ointment bases, tablet binders, film coatings, and
lubricants.[17] PEG is also used in lubricating eye drops.
● PEG, when labeled with a near-infrared fluorophore,
has been used in preclinical work as a vascular agent,
lymphatic agent, and general tumor-imaging agent by
exploiting the enhanced permeability and retention
effect of tumors.[18]
● High-molecular-weight PEG (e.g., PEG 8000) has been
shown to be a dietary preventive agent against colorec-
tal cancer in animal models.[19]
● The chemoprevention database shows PEG is the most
effective known agent for the suppression of chemical
carcinogenesis in rats. Cancer prevention applications
in humans, however, have not yet been tested in clinical
trials.[20]
● The injection of PEG 2000 into the bloodstream of
guinea pigs after spinal cord injury leads to rapid recov-
ery through molecular repair of nerve membranes.[21]
The effectiveness of this treatment to prevent paraple-
gia in humans after an accident is not known yet.
● Research is being done in the use of PEG to mask anti-
gens on red blood cells. Various research institutes have
reported that using PEG can mask antigens without
damaging the function and shape of the cell.
● Research is also being done on the use of PEG in the
field of gene therapy.
● PEG is being used in the repair of motor neurons dam-
Pharmaceutical—Plant Oil
aged in crush or laceration incidents in vivo and in
vitro. When coupled with melatonin, 75% of damaged
sciatic nerves were rendered viable.[22]
● PEG is commonly used as a precipitant for plasmid
DNA isolation and protein crystallization. X-ray dif-
fraction of protein crystals can reveal the atomic struc-
ture of the proteins.
Pharmaceutical Polymers
● In microbiology, PEG precipitation is used to concentrate
viruses. PEG is also used to induce complete fusion
(mixing of both inner and outer leaflets) in liposomes
reconstituted in vitro.
● Gene therapy vectors (such as viruses) can be PEG-
coated to shield them from inactivation by the immune
system and to de-target them from organs where they
may build up and have a toxic effect.[23] The size of the
PEG polymer has been shown to be important, with
larger polymers achieving the best immune protection.
● PEG is a component of stable nucleic acid lipid particles
(SNALPs) used to package siRNA for use in vivo.[24,25]
● In blood banking, PEG is used as a potentiator to
enhance the detection of antigens and antibodies.[26]
● When working with phenol in a laboratory situation,
PEG 300 can be used on phenol skin burns to deactivate
any residual phenol.
PEGylation
PEGylation has become a well-accepted method for the
delivery of biopharmaceuticals especially peptide and pro-
tein. PEGylation is the process of covalent attachment of
PEG polymer chains to another molecule, normally a drug
or therapeutic protein. PEGylation is routinely achieved by
incubation of a reactive derivative of PEG with the target
molecule. Those in the biomedical, biotechnical, and phar-
maceutical communities have become quite familiar. In its
most common form poly(ethylene glycol), with the
improved pharmacological and biological PEG, is a linear
or branched polyether terminated properties that are asso-
ciated with the covalent of poly(ethylene glycol) or PEG to
therapeutically useful polypeptides.
PEGylation, the covalent attachment of PEG to mole-
cules of interest, has become a well-established prodrug
delivery system.[27,28] This polymer is nontoxic, non-immu-
nogenic, non-antigenic, and highly soluble in water and
FDA approved. The PEG-drug conjugates have several
advantages: a prolonged residence in body, a decreased
degradation by metabolic enzymes, and a reduction or
elimination of protein immunogenicity. PEGylation now
plays an important role in drug delivery, enhancing the
potentials of peptides and proteins as therapeutic agents.
The covalent attachment of PEG to a drug or therapeutic
protein can “mask” the agent from the host’s immune sys-
tem (reduced immunogenicity and antigenicity), and
increase the hydrodynamic size (size in solution) of the
agent, which prolongs its circulatory time by reducing
renal clearance. PEGylation can also provide water solubil-
ity to hydrophobic drugs and proteins. PEGylation is a pro-
cess of attaching the strands of the polymer PEG to
molecules most typically peptides, proteins, and antibody
fragments that can help to meet the challenges of improv-
ing the safety and efficiency of many therapeutics.[29] It
produces alterations in the physiochemical properties
including changes in conformation, electrostatic binding,
 Pharmaceutical Polymers
hydrophobicity, etc. These physical and chemical changes
increase the systemic retention of the therapeutic agent.
Also, it can influence the binding affinity of the therapeutic
moiety to the cell receptors and can alter the absorption and
distribution patterns. Typically, most of the PEG-based
prodrugs have been developed for the delivery of antican-
cer agents such as paclitaxel, methotrexate, and cisplatin.
High-molecular-weight prodrugs containing cytotoxic
components have been developed to decrease peripheral
side effects and to obtain a more specific administration of
the drugs to the cancerous tissues.[30]
PEGylation, by increasing the molecular weight of a
molecule, can impart several significant pharmacological
advantages over the unmodified form, such as:
● Improved drug solubility
● Reduced dosage frequency, without diminished effi-
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cacy with potentially reduced toxicity
● Extended circulating life
● Increased drug stability
● Enhanced protection from proteolytic degradation
Starch is one of the superior known natural and biode-
gradable biopolymers. Starch and its derivatives received
much concentration in the food, plastic, and pharmaceuti-
cal industries because of its gelling, film forming, and bio-
degradable properties.[31] Different modifications or
derivatization techniques have been tried for developing
new polymers from natural biopolymers. One approach is
acetylation of starch, which converts the hydrophilic starch
to hydrophobic starch acetate. Starch acetate has been
broadly used for drug delivery applications. Acetylation of
starch has received much attention for varied drug delivery
applications, such as in the preparation of coatings for the
sustained release of drugs. Hydrophobically modified
polymers have attracted much attention in drug delivery
applications due to their fine balance of hydrophilic–hydro-
phobic nature and biodegradability.[32,33] Starch was allowed
to react with acetic anhydride (1:4 ratio) with sodium
hydroxide as a catalyst as per the reported method.[34] Tight
junction visualization studies demonstrated that PEGylated
starch acetate nanoparticles are capable of opening tight
junctions. The control Caco-2 cells stained with rhodamine
phalloidin, to visualize actin, showed uniform staining pat-
tern as shown in Fig. 2(A). However, cells treated with
PEGylated starch acetate nanoparticles displayed a dis-
rupted staining pattern [Fig. 2(B)]. The untreated cells
were observed as smooth lines at the cell–cell junction
[Fig. 2(C)]; whereas, for PEGylated starch acetate nanopar-
ticle-treated cells the staining intensity was weaker at cell–
cell contact sites [Fig. 2(D)].
The use of PEGylated starch acetate nanoparticles for
controlled drug deliveries utilize its self-aggregation prop-
erty. Micellar nanoparticles are formed on the self-associa-
tion of PEGylated starch acetate in the presence of aqueous
insulin solution. The hydrophobic core of starch acetate
5935
protects insulin from the gastric environment. It has been
demonstrated that the insulin released from these nanopar-
ticles was stable with no conformational changes. PEG-
modified starch acetate is a good approach for the controlled
delivery of insulin or other proteins for various therapeutic
applications.[35]
POLYVINYL ALCOHOL AND POLYVINYL
PYRROLIDONE
A polyvinyl pyrrolidone was the first synthetic polymer
used as a blood substitute. Its solutions were mainly used
to treat the shock after the burns and in the case when the
blood transfusion was not indicated.[36–38]
Likewise, the solutions of PVA have found applications
as blood substitutes. However, they were withdrawn from
the list of the blood substitutes as result of their undesirable
side effects. The blood substitutes with the therapeutic
action have also been elaborated as a result of incorpora-
tion of some therapeutic agents (e.g., penicillin, pelentanic
acid, p-aminosalicylic chloride) into PVA.[36,38] PVA has a
hydroxyl group in its structure. It is synthesized by the
polymerization of vinyl acetate to polyvinyl acetate
(PVAc), which is then hydrolyzed to get PVA. PVA hydro-
gels have been used for various biomedical and pharma-
ceutical applications.[39] PVA hydrogels have certain
advantages, which make them ideal candidates for bioma-
terials. Advantages of PVA hydrogels are that they are non-
toxic, non-carcinogenic, and bioadhesive in nature. PVA
also shows a high degree of swelling in water (or biological
fluids) and a rubbery and elastic nature and therefore
closely simulates natural tissue and can be readily accepted
into the body. PVA gels have been used for contact lenses,
the lining for artificial hearts, and drug-delivery applica-
tions. PVA is mainly used in topical pharmaceutical and
ophthalmic formulations.[40,41] It is used as a stabilizer in
emulsions. PVA is used as a viscosity increasing agent for
viscous formulations such as ophthalmic products. It is
used as a lubricant for contact lens solutions, in sustained
release oral formulations, and transdermal patches.[42]
HYDROCOLLOID
Hydrocolloids refer to a range of polysaccharides and
proteins that are nowadays widely used to perform a num-
ber of functions in the pharmaceutical and biomedical
sector. The specific application of plant-derived hydrocol-
loids in pharmaceutical formulations include their use in
Pharmaceutical—Plant Oil
the manufacture of solid monolithic matrix systems,
implants, films, beads, microparticles, nanoparticles,
inhalable and injectable systems, as well as viscous liquid
formulations.[43–47] The hydrocolloids are available in a
wide range and variety, which can be modified depending
upon research requirement. The selection of appropriate
hydrocolloid is dictated by the functional characteristics
 5936 Pharmaceutical Polymers
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Fig. 2 Confocal images (20×) of Caco 2 cell-actin. (A) Caco cells without any treatment (control). (B) Caco cells exposed to 5 mg of
SA-PEG1900 nanoparticles for 1 hr—tight-junction protein ZO-1. (C) Caco cells without any treatment (control). (D) Caco cells exposed
to 5 mg of SA-PEG1900 nanoparticles for 1 hr.
Source: From Minimol et al.[35] © 2013, with permission from Elsevier.

required; moreover it is inevitably influenced by price.
A lot of work has been carried out on various hydrocol-
loids in the field of scientific research. The biomedical
and pharmaceutical applications of hydrocolloid-based
polymer hydrogels are of greater importance because of
properties such as biocompatibility, non-toxicity, equilib-
rium swelling, and renewability. Hydrocolloids are often
utilized in the design of novel drug delivery systems such
as those that target the delivery of the drug to a specific
region in the gastrointestinal tract or in response to exter-
nal stimuli to release the drug. This can be done via differ-
ent mechanisms including the coating of tablets with
polymers having pH-dependent solubilities or incorporat-
Pharmaceutical—Plant Oil
degraded by the bacterial polysaccharidases. This property
makes these hydrocolloids exceptionally suitable for the
formulation of colon-targeted drug delivery systems.[48]
PLASTICS AND RUBBERS
Plastics are synthetic materials, which mean that they are
artificial or manufactured. Synthesis means that “some-
thing is put together,” and synthetic materials are made of
building blocks that are put together in factories. Plastics
and natural materials such as rubber or cellulose are com-
posed of very large molecules called polymers. Plastics are

ing non-digestible polymers that are degraded by bacterial
enzymes in the colon. Non-starch, linear polysaccharides
are resistant to the digestive action of the gastrointestinal
enzymes and retain their integrity in the upper gastroin-
testinal tract. Matrices manufactured from these hydro-
colloids therefore remain intact in the stomach and the
small intestine, but once they reach the colon they are
polymers, but polymers do not have to be plastics. The way
plastics are made is actually a way of imitating nature,
which has created a huge number of polymers. Cellulose,
the basic component of plant cell walls, is a polymer and
so are all the proteins produced in the body and the pro-
teins one eats. Another famous example of a polymer is
DNA—the long molecule in the nuclei of ones cells that
 Pharmaceutical Polymers
Fig. 3 Polyethylene.
Downloaded by [Narendra P. S. Chauhan] at 00:27 14 April 2016
Fig. 4 Structure of cellulose.
carries all the genetic information about oneself. Wool,
cotton, silk, wood, and leather are examples of natural
polymers that have been known and used since ancient
times. This group includes biopolymers such as proteins
and carbohydrates that are constituents of all living organ-
isms. Synthetic polymers, which include the large group
known as plastics, came into prominence in the early 20th
century. An artificial polymer that is known to everyone in
the form of flexible, transparent plastic bags that is poly-
ethylene. It is also the simplest polymer, consisting of
random-length (but generally very long) chains made up of
two-carbon units (Fig. 3).
The largest single use of rubber is the production of
vehicle tires. Tires are highly engineered products that use
different kinds of rubber in different parts.
Rubber is used in the pharmaceutical industry to make
closures, cap liners, and bulbs for dropper assemblies. The
rubber stopper is used mainly for multiple dosage vials and
disposable syringes. The rubber polymers most commonly
used are natural, neoprene, and butyl rubber. Butyl rubbers
and nitrile rubbers are some of the synthetic rubbers used
for the manufacturing of closures.
CELLULOSE-BASED POLYMER
Polysaccharides, natural polymers, fabricated into hydro-
philic matrices stay accepted biomaterials for controlled-
release dosage forms. Cellulose is the most abundant
naturally occurring biopolymer.[49,50] A variety of natural
fibers such as cotton and higher plants have cellulose as a
main constituent.[51,52] It consists of long chains of anhydro-
D-glucopyranose units (AGU) with each cellulose mole-
cule having three hydroxyl groups per AGU, with the
exception of the terminal ends shown in Fig. 4.
5937
Cellulose is insoluble in water and the most common
other solvent. In spite of its poor solubility, cellulose is
used in many applications including composites, netting,
upholstery, coatings, packing, paper, etc. Cellulosics (cel-
lulose derivatives) are in general strong, reproducible,
recyclable, and biocompatible,[53] being used in various
biomedical applications such as blood purification mem-
branes and the like.
Pharmaceutical Uses of Cellulose and Cellulose
Derivatives
Methylcellulose
MC resembles cotton in appearance and is neutral, odorless,
tasteless, and inert. When MC contacts with water, it swells
and reproduces a clear to opalescent, viscous, colloidal
solution and it is insoluble in most of the common organic
solvents. Solutions of MC are stable over a wide range of
pH (2 to 12) with no change in viscosity. They can be used
as bulk laxatives, so it can be used to treat constipation, and
in nose drops, ophthalmic preparations, burn preparations
ointments, and like preparations.
Ethylcellulose
EC is the non-ionic, pH-insensitive cellulose ether and is
Pharmaceutical—Plant Oil
insoluble in water but soluble in many polar organic sol-
vents. It can be used on its own and in combination with
water-soluble polymers to prepare sustained release film
coatings that are frequently used for the coating of micro-
particles, pellets, and tablets. Many researchers like Fried-
man and Golomb.[54] and Soskolne et al.[55] have confirmed
the ability of EC to sustain the release of drugs.
 5938
Sodium carboxymethyl cellulose
It is a low-cost commercial soluble and polyanionic poly-
saccharide derivative of cellulose that has been used in
medicine, as an emulsifying agent in pharmaceuticals, and
also used in cosmetics.[56] Carboxymethyl cellulose (CMC)
is one of the important cellulose derivatives in industries,
which is widely used as an anti-caking agent, emulsifier,
stabilizer, dispersing agent, thickener, and gelling agent.
Sodium carboxymethyl cellulose is used in both therapeu-
tic and excipient. Therapeutic uses include bulk-forming
laxatives in which it may be the primary ingredient. Excip-
ient uses include those of suspending, tablet binding, or
viscosity increasing.
Hydroxypropylcellulose
Downloaded by [Narendra P. S. Chauhan] at 00:27 14 April 2016
Hydroxypropylcellulose (HPC)-SL and low-viscosity HPC
polymers are versatile pharmaceutical excipients. It is
widely used in pharmaceutical formulations like in oral
products, as a tablet binder, in film-coating, and as a con-
trolled-release matrix. All of the cellulosic polymers
described in the previous section have been used as binders
for solid dosage forms in wet granulation and dry- or
direct-compression tableting processes.[57–59]
REVERSE MICELLES FOR PHARMACEUTICAL
APPLICATIONS
Polymeric micelles are core–shell structures formed through
the self-assembly of amphiphilic polymers in a solvent that
is considered hostile toward either moiety. In water, these
micelles are characterized by a hydrophobic core shielded
from the external medium by a hydrophilic shell. This par-
ticular type of micelle has been extensively studied with a
particular attention to their ability to improve the aqueous
solubility of hydrophobic therapeutic agents.[60,61] Polyami-
doamine-based reverse micelles (RMs) were also proposed
for the controlled delivery of the anticancer drug 5-fluoro-
uracil. However, moderate success was obtained, since in
vitro an aqueous dispersion of the micellar formulation
induced less than 5% drug release over 7 hr.[62] Vasopressin
(9 amino acids, 1084 Da), also known as the antidiuretic
hormone, is naturally secreted in response to changes in
blood pressure or volume.[63]
It is highly soluble in water but has incomplete affinity
for apolar solvents such as ethyl oleate, as indicated by a
low Kapp (b0.05) (Fig. 5). However, in the presence of RMs,
Pharmaceutical—Plant Oil
the resemblance of vasopressin for the oil phase was sig-
nificantly enhanced.[64] Thus, SA-YCZ RMs seems better
suited for the encapsulation of peptidic molecules with a
MW not exceeding a few 1000 Da. All alkylated star-
shaped polymers are referred to as SA-YCZ, where A, Y,
and Z are the degree of branching, alkyl chain length and
DA respectively. According to Fig. 5 at an initial loading of
Pharmaceutical Polymers
Fig. 5 Partition of vasopressin between ethyl oleate and water in
the presence of RMs composed of S4-12C60 (circles), S4-14C60
(squares), and S4-18C60 (open triangles). Blank ethyl oleate was
used as control (closed triangles). Kapp values were calculated
from the ratio of mean peptide concentrations in oil and water.
Source: From Jones et al.[64] © 2008, with permission from
Elsevier.
12.5 µg, the experimental Kapp was maximal and reached 2,
4, and 77 for the C12, C14, and C18 derivatives, respec-
tively. The ability of RMs to solubilize vasopressin in oil
decreased with increasing peptide loading until saturation
of the available space was achieved, as indicated in Fig. 5.
FILM FORMING (COATING)
Film coating is one of the most commonly used methods
for the preparation of sustained and controlled release dos-
age forms leading to the evaluation of various materials
with film-forming property.[65] The drug delivery applica-
tions of polymer or biomaterial films are well established
for providing protective coatings and controlled drug
release from dosage forms.[66] The main parameters used
to characterize the film-forming materials for coating
purposes are mechanical properties,[67,68] permeability
properties,[69] and WVTRs.[70] Coated formulations for drug
release behavior have been investigated for different condi-
tions by various investigators.[71–73]
Aqueous film coating applications are either solutions
or dispersions, depending on the water solubility of the
film former polymers. Film formation from the polymer
solution occurs through a series of phases. When the poly-
mer solution is applied to the surface of the tablet, cohesion
forces form a bond between the coating polymer mole-
cules. Film formation from dispersion occurs when poly-
meric particles coalesce to form a continuous film (Fig. 6),
making it a more complex mechanism compared to film
formation from solution.[74]
 Pharmaceutical Polymers 5939

POLYDIMETHYLAMINOETHYLMETHACRYLATE Figure 8 shows the in vitro release profile of Eudragit-

A poly[2-(dimethylamino)ethylmethacrylate] (PD), bio-
compatible, water-soluble polymer finds extensive applica-
tions as membranes,[75] efficient non-viral gene-delivery
vectors,[76] antimicrobial agents,[77] and biosensors.[78]
N-hydroxypropyltrimethylammonium polydimethyl-
aminoethylmethacrylate (PDG) prepared by the quater-
nization reaction of PD was conducted using
N-hydroxypropyltrimethylammonium chloride as the qua-
ternizing agent. Swelling of polymers or drug-polymer
matrices in the dissolution test media have been reported
according to significant effects on ordinary dosage forms
and controlled drug release systems. Atomic force micros-
copy (AFM) image shown in Fig. 7(A) confirms the
morphology and size of PDG. The swelling profile of PDG
at pH 1.2 and 6.8 is depicted in Fig. 7(B). PDG particles
Downloaded by [Narendra P. S. Chauhan] at 00:27 14 April 2016
coated insulin-loaded PDG at gastric and intestinal pH.
PDG exhibited encapsulation efficiency of 85.5 ± 3.24%.
Due to the swelling nature of the particles at pH 1.2, the
particles were coated with Eudragit L 100-55. About 1.5%
of insulin was released at gastric conditions whereas about
30% of insulin was released at intestinal pH in the first
hour. The results are statistically significant as the P-value
was found to be less than 0.05. ELISA and Circular dichro-
ism studies proved that the insulin released from PDG was
capable of retaining its biological activity.
PDG having high positive charge displayed a calcium bind-
ing property, which helped in the loosening of epithelial tight
junctions by actin filament dislocation and binding to ZO-1
proteins. The PDG polymer is mucoadhesive thereby making
it a suitable carrier for the mucosal delivery of proteins.
Recently, a number of terpolymers derived from 4-acetyl-

exhibited a high percentage of swelling at acidic pH pyridineoxime, 4-chloroacetophenone oxime, 8-hydroxy-

whereas the degree of swelling was lower at intestinal pH. quinoline, formaldehyde, benzoic acids, furfural, and
P-value as determined by Student’s t-test was found to be substituted acetophenones have been reported with excel-
statistically significant.[79] lent antimicrobial properties.[80–84]

Fig. 6 Film formation from aqueous polymeric dispersion.

Pharmaceutical—Plant Oil

Fig. 7 (A) AFM of N-hydroxypropyltrimethylammonium polydimethylaminoethyl methacrylate and (B) swelling profile of N-hydroxy-
propyltrimethylammonium polydimethyl aminoethylmethacrylate at pH 1.2 and 6.8. Indicated values are the mean of three measurements
(±SD) (n = 3).
Source: From Sonia & Sharma[79] © 2013, with permission from Elsevier.
 5940
Fig. 8 In vitro release profile of N-hydroxypropyltrimethylam-
monium polydimethyl aminoethylmethacrylate at pH 1.2 and 6.8.
Downloaded by [Narendra P. S. Chauhan] at 00:27 14 April 2016
Each data point is the mean of three measurements (±SD) (n = 3).
Source: From Sonia & Sharma[79] © 2013, with permission from
Elsevier.
CONCLUSION
Polymeric substances are in contact with drugs not only as
ingredients in final dosage forms but also as processing
aids or packaging materials. In conventional dosage forms,
the majority of polymers used as excipients are natural
polymers and many are included in the GRAS list as a
result of a long history of pharmaceutical marketing. In
pharmaceutical packaging, polyethylene, polypropylene,
and PVC have been used most widely. There is a trend,
however, to replace them with more environment-friendly,
biodegradable polymers. Of the numerous roles played by
polymers in the production of pharmaceutical products,
emphasis often has been placed on the use of polymers in
the fabrication of controlled release drug delivery systems.
Progress in the area of controlled drug delivery has been
possible only as a result of the incorporation of polymer
science into pharmaceutics. The development of sophisti-
cated pharmaceutical products requires multidisciplinary
efforts. Polymers with special or multiple properties need
to be developed to achieve self-regulated drug delivery,
long-term delivery of protein drugs, and drug targeting to
specific organs in the body. These cannot be achieved by
elaborate device design alone. These require the develop-
ment of smart polymeric systems, which recognize and
respond to physiological and pathological processes in the
body. Polymers will remain the indispensable component
in the development of new pharmaceutical products.
Pharmaceutical—Plant Oil
ACKNOWLEDGMENT
One of the authors, Dr. Narendra P. S. Chauhan, is thank-
ful to Elsevier for copyright permission. Authors are
also thankful to Prof. Suresh C. Ameta, Department of
Pharmaceutical Polymers
Chemistry, Pacific College of Basic & Applied Sciences,
PAHER University, Udaipur (Raj.) for suggestions.
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