Polymers in CDDS

POLYMERS IN CONTROLLED DRUG

DELIVERY SYSTEMS
INTRODUCTION:

Controlled drug delivery systems can include the maintenance of drug levels within a desired range, the
need for fewer administrations, optimal use of the drug in question, and increased patient compliance. While
these advantages can be significant, the potential disadvantages cannot be ignored like the possible toxicity
or non-biocompatibility of the materials used, undesirable by-products of degradation, any surgery required
to implant or remove the system, the chance of patient discomfort from the delivery device, and the higher
cost of controlled-release systems compared with traditional pharmaceutical formulations. The ideal drug
delivery system should be inert, biocompatible, mechanically strong, comfortable for the patient, capable
of achieving high drug loading, safe from accidental release, simple to administer and remove, and easy to
fabricate and sterilize. The goal of many of the original controlled-release systems was to achieve a delivery
profile that would yield a high blood level of the drug over a long period of time. With traditional drug
delivery systems, the drug level in the blood follows the in which the level rises after each administration
of the drug and then decreases until the next administration. The key point with traditional drug
administration is that the blood level of the agent should remain between a maximum value, which may
represent a toxic level, and a minimum value, below which the drug is no longer effective.

Control of drug diffusion from the dosage form is a logical approach for drugs that require frequent
administration to maintain therapeutic levels in the body. However, major limitations are imposed on
maintaining controlled drug delivery by the normal physiological processes of the body, and by how much
drug can be enclosed conveniently in a single dosage form. For example, retardation of diffusion alone
cannot be used to extend the duration of release of a drug from an oral dosage form beyond its transit time
in the gastrointestinal tract. For drugs that require large doses, few patients would be compelled to swallow
a 5- or 10-g tablet or capsule, or even several smaller tablets or capsules at one time. Drugs that undergo
extensive first-pass metabolism are also poor candidates for the development of a controlled-release dosage
form.

Polymers can be used to control the diffusion of drugs by (1) controlling how rapidly the drug molecules
move through the polymer molecular matrix, or by (2) controlling the movement of dissolved drug
molecules through channels or pores in a matrix permeated by the dissolution medium. In the first case, the

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rate of diffusion depends on the solubility of the drug in the polymer matrix, the size of the drug molecules,
and the hindrance of movement by the matrix structure. In the second case, the rate of diffusion depends
on the availability, length, and tortuosity of the pores; the solubility of the drug in the penetrating medium;
and the medium’s viscosity. In a given microcapsule, both mechanisms may contribute to the movement of
the drug molecules into the dissolution environment. The extent of contribution by each mechanism will
depend on the nature of the drug, the polymer, other microcapsule parameters, and the dissolution
environment. Control of drug release with a polymer also can be accomplished by erosion of the polymer

to release the drug, or by a combination of drug diffusion and polymer erosion.

POLYMER USED IN CONTROL DRUG DELIVERY SYSTEM:

Polymers are becoming increasingly important in the field of drug delivery. The pharmaceutical
applications of polymers range from their use as binders in tablets to viscosity and flow controlling agents
in liquids, suspensions and emulsions. Polymers can be used as film coatings to disguise the unpleasant
taste of a drug, to enhance drug stability and to modify drug release characteristics. The review focuses on
the significance of pharmaceutical polymer for controlled drug delivery applications. Sixty million patients
benefit from advanced drug delivery systems today, receiving safer and more effective doses of the
medicines they need to fight a variety of human ailments, including cancer. Controlled Drug Delivery
(CDD) occurs when a polymer, whether natural or synthetic, is judiciously combined with a drug or other
active agent in such a way that the active agent is released from the material in a predesigned manner. The
release of the active agent may be constant over a long period, it may be cyclic over a long period, or it
may be triggered by the environment or other external events. In any case, the purpose behind controlling
the drug delivery is to achieve more effective therapies while eliminating the potential for both under and
overdosing.

The goal of the original controlled release system was to achieve a delivery profile that would yield over a
long period of time traditional tablets or injections, the drug level in the blood follows the profile shown in
figure la, in which the level rises after each administration of the drug and then decreases until the next
administration. The key point with traditional drug administration is that the blood level of agent should
remain between a maximum value, which may represent a toxic level and a minimum value, below which
the drug is no longer effective. In controlled drug delivery system designed for long term administration,
the drug level in the blood follows a profile shown in the figure , remaining constant between the desired
maximum and minimum, for an extended period of time depending on the formulation and the application.
this time may be anywhere from 24 hrs [procardia XL] to 1 month [luprondrpot] to 5 years (norplants].

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Polymers in CDDS

Fig.: Drug levels in plasma released from (-----) conventional drug delivery system and (—) controlled
drug delivery system.

Since the drug release rate should be by designed a constant, then following kinetic theory, the pattern of
drug administration into the body will follow zero order kinetics. While zero order-released system has
been known for some time, what particularly marked the innovative pharmacological work of the past
decade has been the development of biodegradable polymeric system. Following implantation of drug
polymeric carrier, the drug is continuously released into the body, the polymeric drug carriers materials
begins to hydrolyse or otherwise degrade. These polymeric drug carriers are most often synthesized from
the monomers which are the part of human metabolic path-way. These polymers hydrolyse to parent
monomers and are themselves subsequently metabolized, hence the terminology biodegradable drug
delivery system. Because these polymers are synthesized metabolic monomers and hydrolysed to their
native components, these materials have been found to be tissue compatible.

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Polymers in CDDS

CONTROLLED DRUG DELIVERY SYSTEM

Controlled drug delivery systems are designed to release drugs in a predetermined manner, providing
sustained or targeted delivery over an extended period. This approach enhances therapeutic effectiveness,
reduces side effects, and improves patient compliance. These systems often employ specialized carriers or
formulations that control the release rate, duration, and site-specific targeting of the drug. Examples include
microspheres, liposomes, and implants. The precise control afforded by these systems allows for a more
predictable and optimized drug release profile, contributing to improved treatment outcomes in various
medical applications.

Controlled drug delivery systems can be categorized into various types based on their design and release
mechanisms. Here are some key categories:

• Transdermal drug delivery system:

Transdermal drug delivery system (TDDS) is one of the systems lying under the category of controlled
drug delivery, in which the aim is to deliver the drug through the skin in a predetermined and controlled
rate. Transdermal Drug Delivery System are defined as self contained, discrete dosage forms which are
also known as ‘patches’ when patches are applied to the intact skin, deliver the drug through the skin at a
controlled rate to the systemic circulation. The main objective of transdermal drug delivery system is to
deliver drugs into systemic circulation through skin at predetermined rate with minimal inter and intra
patient variation. Currently transdermal delivery is one of the most promising methods for drug application.

The scheme provides a large surface area for diffusion. It has also been shown that the benefit of intravenous
drug infusion can be closely duplicated by continuous transdermal drug administration through intact
scheme. A transdermal system consists of a reservoir containing the drug dispersed as a separate phase with
in a highly permeable matrix. This is laminated between the rate controlling microporous membrane and
external backing that is impermeable to drug and moistures.

Example: nicotine patches or patches that contain painkillers, such as prescription opioids

• Implantable drug delivery system:

Implant drug delivery systems (IDDSs) are very attractive for a number of classes of drugs, particularly
those that cannot be delivered via the oral route, are irregularly absorbed via the gastrointestinal tract, or
that benefit from site-specific dosing, Examples include steroids, chemotherapeutics, antibiotics, analgesics
and contraceptives, and biologics such as insulin or heparin (Implants can be used as delivery systems for
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Polymers in CDDS

either systemic or local therapeutic effects. For systemic therapeutic effects, implants are typically
administered SC. intramuscularly, or intravenously, whereby the incorporated drug is delivered from the
implant and absorbed into the blood circulation) Implants for local effects are placed into specific body
sites, where the drug acts locally, with relatively negligible absorption into the systemic circulation)
Implants are typically designed to release the incorporated drug in a controlled manner, allowing the
adjustment of release rates over extended periods of time, ranging from several days to years.

• Ocular Delivery Systems:

The eye doesn't serve as a portal for systemic treatment but controlled release devices have been introduced
for localised treatment. The ocusert ocular therapeutic system for the release of pilo-carpine in the treatment
of glaucoma was the first diffusion controlled system marketed. This unit consists of a drug reservoir
between two soft membrane outer layers. The outer layers are made of microporous ethylene-vinyl-acetate
copolymers membranes. Recently an epinephrine releasing ocular therapeutic system was also developed.
Topical steroids, such as prednisolone acetate and hydrocortisone acetate, have been formulated into ocular
inserts.

• Nasal delivery systems:

Intranasal administration appear to be ideal alternative to the parenteral for systemic drug delivery. Various
bio adhesive polymers such as methyl cellulose, carboxy methyl cellulose, hydroxy propyl cellulose, poly
acrylic acid have been used to enhance nasal drug absorption.

• Intrauterine drug delivery:

Oral contraceptive pills and intrauterine contraceptive devices (IUD’s) are the most effective temporary
methods of fertility regulation. There are two types of IUD’s: Medicated and non medicated. Two classes
of medicated IUD’s are available: The copper bearing IUD or the progesterone releasing IUD (eg-
progestasert).

Progestasert is a T-shaped progesterone releasing IUD in which a drug containing forms an integral part of
the vertical limb of the polyethylene T-device.

• Oral delivery systems:

Oral drug delivery has been known for decades as the most widely utilised route of administration among
all the routes that have been explored for the systemic delivery of drugs in different dosage forms. Recently,
several technical advancement have been made. They have resulted in the development of new techniques
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Polymers in CDDS

for the drug delivery. These techniques are capable of controlling the rate of drug delivery system that can
be utilised for the controlled delivery of drugs in the alimentary canal by the use of polymers only. Some
of the novel drug delivery systems for oral controlled release drug administration includes.

(a) Pressure-Controlled Gastrointestinal delivery system:

These systems are fabricated by encapsulating an osmotic drug core containing an osmotically active drug
within a semipermeable membrane made from biocompatible polymers eg. Cellulose acetate. A delivery
orifice with a controlled diameter is drilled through the coating membrane for controlling the release of
drug solutes. An eg. of such type of system include Acutrim tablet which contain phenyl- propanol amine
as the drug.

(b) Gel diffusion – controlled gastrointestinal delivery system:

This type of gastrointestinal delivery system is fabricated from gel forming polymers such as carboxy
methyl cellulose. These are prepared by first dispersing the therapeutic dose of a drug in layer of water
soluble CMC, sandwiching the drug loaded CMC layers between layers of cross linked CMC and then
compressing these layers to form a multilaminated device. This device can be further coated with a polymer
coating material to form a delivery device.

(c) Bio (muco) adhesive drug delivery system:

Mucoadhesive polymers can be used to extended the gastrointestinal Itansist time. A mucoadhesive
polymer is natural or synthetic polymer capable of producing an adhesive interaction with a biological
membrane, which is then called a bio-adhesive polymers. A no. Of commonly used macromolecular
pharmaceutical excipients have been evaluated and found to have bio(muco) adhesive properties.

Many mucoadhesive gastrointestinal drug delivery system have been developed. One such system is a
mucoadhesive microsphere that consists of a drug dispersed hydrogel matrix fabricated from polyhydroxy
methacrylate (p- HEMA) and a mucoadhesive coating of carbopol 934.

(d) Oral Mucosal drug delivery:

It has been known that after buccal and sublingual administration drugs solutes are rapidly absorbed into
the reticulated vein and then drained into the systemic circulation. There fore, the buccal and sublingual
routes of administration can be utilised to bypass the hepatic-first- pass elimination of drugs.

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Polymers in CDDS

The oral mucosal bioadhesive drug delivery system is designed to be applied to an oral mucosal site. It
consists of a polymeric adhesive composition that, in contact with saliva, becomes adhesive and renders
the system attached to the oral mucosa. The system can be designed to stay in a fixed position on the oral
mucosa for a duration of upto 12 hours, during which the solutes are continuously released into the oral
cavity for transmucosal absorption into the systemic circulation Several polymeric adhesive composition
have been developed:

1.Severalose (>80%) and ethyl cellulose (<20%)

2. Hydroxy propyl cellulose (0.02-2%) and polyacrylicacid sodium salt (0.27%).

3 Sodium polyacrylate (10-60%)

4. Alkylacrylate (<30%) and acrylamide vinyl pyrrolidone (>70%)

A typical eg. Of the application of these adhesive composition in the formulation of saliva-activated oral
mucosal bioadhesive drug delivery system is demonstrated by the development of the susadrin trans
mucosal tablet. This tablet contains hyroxypropyl cellulose and ethyl cellulose together in a dry state as the
polymer system. It is designed to be adhere to the buccal mucosa between the lip and gum about the upper
incisors or between the cheek and gum for a duration of upto 6 hours.

ADVANTAGES OF CONTROLLED DRUG DELIVERY SYSTEM:

1. Maintains the drug level within the desired range.

2. Useful for delivery of ‘difficult’ drugs: the slow release of water- soluble drugs, and/or fast release of
poorly soluble drugs,

3. Reduces dosing frequency

4. Avoids over or under dosing,

5. Prevention or reduction of side effects,

6. Reduction in total health care cost

7. Improved efficacy in the treatment,

8. Reduction in adverse side effects and improvement in tolerability

9. Improved patient compliance

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Polymers in CDDS

10. Uses less amount of total drug,

11. Minimizes or removes local or systemic side effects.

12. Minimal drug accumulation on chronic usage

13. Cures or controls the condition more promptly

14. Reduces the fluctuation in drug level

15. Improves the bioavailability of some drugs.

DISADVANTAGES OF CONTROLLED DRUG DELIVERY SYSTEM:

1. May be costly,

2. Unpredictable and often provide poor in-vitro - in-vivo correlations,

3. May cause dose dumping, if the release design is failed,

4. Provides less scope for dosage adjustment,

5. May increase the first pass clearance,

6. Poor systemic availability in some cases,

7. Effective drug release period is influenced and limited by the gastric residence time.

8. All drugs are not suitable for formulating into ER dosage form.

9. Irretrievable
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Polymers in CDDS

POLYMERS
The word “polymer” is derived from the Greek (poly) for “many” and (meres) for “part,” meaning a long-
chain consisting of many parts. Polymers are large or macromolecules having high molecular weight
composed of several small repeating units. These are formed from small molecules called monomers
through a process known as polymerization.

Polymers can be used to control the diffusion of drugs by (1) controlling how rapidly the drug molecules
move through the polymer molecular matrix, or by (2) controlling the movement of dissolved drug
molecules through channels or pores in a matrix permeated by the dissolution medium. In the first case, the
rate of diffusion depends on the solubility of the drug in the polymer matrix, the size of the drug molecules,
and the hindrance of movement by the matrix structure. In the second case, the rate of diffusion depends
on the availability, length, and tortuosity of the pores; the solubility of the drug in the penetrating medium;
and the medium’s viscosity. In a given microcapsule, both mechanisms may contribute to the movement of
the drug molecules into the dissolution environment. The extent of contribution by each mechanism will
depend on the nature of the drug, the polymer, other microcapsule parameters, and the dissolution
environment. Control of drug release with a polymer also can be accomplished by erosion of the polymer
to release the drug, or by a combination of drug diffusion and polymer erosion.

BIODEGRADABLE POLYMERS:

Polymers which degrade in biological fluids when incorporated in DDS and result in the release of dissolved
or dispersed drug are called biodegradable polymers. They are used as they offer advantages like the DDS
is not required to be removed from the body (as it degrades in the body) and the products of degradation
are natural and biocompatible thus minimising the concern of toxicity. Biodegradable polymers can be used
in contraceptive implants and injections which are capable of constantly releasing the contraceptive for up
to one year, and in anticancer DDS that help in achieving specific drug concentrations at the site of cancer.

The following classes of biodegradable polymers have been employed in DDS.

1. Lactide / Glycolide Polymers –

These polymers show predictable kinetics of biodegradation, are biocompatible, can be easily incorporated
into DDS and have been approved by regulatory authorities for their use in DDS.

The in vivo degradation of these by their crystallinity and water uptake properties. Crystallinity in turn
depends on stereochemistry and polymer composition, whereas hydrophilicity of these polymers is based
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Polymers in CDDS

on their composition i.e., lactic acid polymers show greater hydrophilicity compared to glycolide polymers.
Thus, by varying the glycolide and lactide ratio, the polymers can be given a varying degree of
hydrophilicity which makes them suitable for incorporation in a wide range of DDS. Even their solubility
depends on the ratio of lactide to glycolide monomers present in them.

These polymers undergo bulk erosion in the body, by cleavage through hydrolysis resulting in the formation
of monomers. The degradation products are removed via Krebs cycle and in urine. Rate of degradation may
vary with temperature, pH or in presence of catalysts. Therefore, they degrade at similar rates at various
sites in the body.

The time in which the polymer gets degraded depends on its composition. For example, poly (/-lactide)
degrades in 18-24 months, poly(glycolide) in 2-4 months, 50:50 (dl-lactide-co-glycolide) in 2 months, etc.

The types of DDS prepared using these polymers include microspheres, microcapsules, implants, fibres etc.
Antibiotics, steroid hormones, anticancer agents, anaesthetics etc., have been incorporated in DDS using
these polymers.

2. Polyanhydrides -

Polyanhydrides show erosion in a controlled heterogeneous fashion and do not require any additives for
erosion. Drugs can be incorporated in polyanhydride matrices. They can also be used in the preparation of
microspheres. These polymers show rapid degradation in basic medium compared to that in medium and
do not erode at very acidic pH values. Drugs that have been incorporated into DDS using these polymers
include cortisone acetate, insulin, bethanechol, bovine growth hormones etc.

3. Poly (Caprolactones) -

This homopolymer degrades very slowly and may be used in DDS that are designed to last for more than a
year. It is capable of forming blends with various polymers like lactic acid, glycolic acid etc. These
derivatives and the homopolymer show high permeability to drugs and are non-toxic

It has a low glass transition temperature, is semi- crystalline and has a melting range of 59-64°C. It is
soluble in chloroform, carbon tetrachloride, toluene, benzene and a number of other solvents at room
temperature. It does not dissolve in petroleum ether, diethyl ether and alcohol, whereas exhibits poor
solubility in acetone, acetonitrile, 2-butanone etc. Microcapsules, films, porous membranes etc., can be
fabricated using these polymers.

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Polymers in CDDS

4. Poly (Orthoesters) -

These polymers are characterized by the presence of acid labile linkages in their structure which help in
alteration of their rate of hydrolysis by attaching acidic or basic excipients while formulating the DDS. An
additional benefit with these polymers is that their erosion is restricted to their surface, thus allowing for
maximum control over the drug release from the DDS.

They are sensitive to acids i.e., degrade rapidly whereas remain stable in basic environment. Therefore,
acidic and basic excipients are used to enhance the rate of hydrolysis and stabilize the interior of the DDS
respectively. As a result, short half-life DDS with rapid surface erosion use acidic excipients whereas for
long-term surface croding devices, basic excipients are used. Implants and oral DDS can be fabricated using
these polymers.

5. Poly (Phosphazenes) -

These polymers are made up of long chains of al- ternating phosphorous and nitrogen atoms. Each
phosphorous atom has two side groups attached to it. Based on the nature of the side groups, polyphos
phazenes are identified to be of various types, hydro- phobic, hydrophilic, insoluble but surface-active and
insoluble biodegradable polyphosphazenes.

The insoluble biodegradable polyphosphazenes are further classified into amino acid ester systems, glyceryl
derivatives and glycosyl derivatives. Polyphosphazene are also ampiphilic i.e., contain both hydrophilic
and hydrophobic groups. Few other act as hydrogels, while few are water soluble and bioactive. All these
categories find suitable applications in the designing of DDS.

6. Pseudopoly (Amino Acids) -

These polymers are made up of simple nutrient amino acids, as a result are expected to be least toxic.
However, these offer the following limitations.

(a) They possess antigenic nature

(b) They are highly water soluble, have high melting points, etc.

(c) They are expensive due to the synthetic method employed in their manufacture

These polymers can be modified structurally to overcome these limitations. For example, tyrosine derived
polymer (imino carbonates) were synthesized to poses the required biocompatibility and mechanical
strength.

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Polymers in CDDS

7. Natural Polymers -

Natural polymers offer several advantages over synthetic biodegradable polymers and hence are
continuously under research for use in DDS designing. They are easily available as they are natural products
of living organisms and inexpensive compared to synthetic forms and can be modified chemically to meet
the desired criteria. Protein like collagen, albumin, gelatin etc. and polysaccharides like starch, dextran etc.,
have been investigated as polymer matrices to be used in DDS, with many protein based DDS formulated
as solid cross- linked microspheres.

Collagen has been used in fabrication of the DDS. It is found in animal tissues as fibres in skin and tendons.
It helps in restricting deformation of tissues thereby preventing mechanical failure. It offers several
advantages like biocompatibility, non- toxicity, easy isolation and purification in large quantities, can be
fabricated in various forms and possess adequately documented structural, physical, chemical and
immunological properties. It’s structure, properties have facilitated it’s fabrication as absorbable sutures,
composite tissue tendon allografts, sponge wound dressing, injectables for facial reconstructive surgery etc.

Polysaccharides that have been used in DDS include starch and it’s derivatives, dextran, insulin and
cellulose. Starch has been combined with acrylic group to give poly(acryl) starch microspheres. Other
polysaccharides like dextran, cellulose and insulin have been used to deliver antibiotics, enzymes etc., thus
acting as carriers

Other natural polymers that have been used in DDS include hyaluronic acid and chitin. Hyaluronic acid is
a constituent of soft connective tissue and is a linear polysaccharide. It has been incorporated in ophthalmic
preparation to improve ocular absorption of timolol. Chitin is a cellulose like biopolymer which has been
used in the form of cross- linked hydrogels of films to deliver drugs.

Advantages :

Biodegradable polymers are preferred over non-biodegradable polymers as they have the following
advantages

1. Biodegradable polymers degrade or break down into biocompatible products that do not cause toxicity
and are easily removed or absorbed by the body. Surgical removal is never required as in the case of
depleted non-biodegradable polymer skeleton.

2. Natural biodegradable polymers are easily available and can be easily isolated and modified into many
forms. They are usually cheap and inexpensive.

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Polymers in CDDS

3. After slow dissolution and erosion, even water insoluble polymers show water soluble degradation
product.

Applications:

The following are the applications of biodegradable polymers.

Biopolymer Applications
1. Polyphosphazenes Used in implantable devices as they show minimum tissue
response
2. Natural polymers
(a) Collagen Can be fabricated to a wide variety of forms.
Used in solid ocular inserts
Carriers of antibiotics and enzymes as they form covalent
(b) Polysaccharides bonds with drugs
E.g. Starch, insulin, Used in ophthalmic preparations to enhance ocular
cellulose, hyaluronic acid absorbance of timolol
Delivery of drugs
(c) Partially deacylated
chitin Used for controlled delivery due to advantage of having
surface erosion. This is used in order to produce Compacts
(d) Polyanhydride for drugs like corticosteroids.

Can be fabricated as thin films or by compression moulding

for drugs like tetracycline etc.
(e) Poly caprolactone
Various types of formulations including implants and oral
delivery system
(f) Polyorthoesters

Biopolymers find their general application in contraceptive implants or injections that are utilised for long
term drug activity. Example: steroids or anti cancer agents

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HYDROGELS:

Certain hydrophilic polymers when placed in water imbibe (absorb) large amounts of water in their
structures and swell. These three dimensional aqueous gel networks are called hydrogels. The networks are
insoluble in water owing to the presence of chemical bonds or physical cross- links like hydrogen bonding,
hydrophobic interactions or tonic interactions. Hence hydrogels can imbibe water about 10-20 times their
molecular weight, swell and then return to their original shape even after a long-term holding.

The high water content of hydrogels contributes to their biocompatibility. Hence hydrogels are used in the
manufacturing of contact lenses, wound dressings, superabsorbents, drug delivery systems, linings artificial
hearts, membranes for biosensors, membranes for artificial skin etc.

On the other hand, if the chemical bonds and physical links are fewer in the hydrophilic polymer, then the
polymer when placed in water dissolve to form a polymer solution known as hydrosol. In simple terms, an
aqueous solution of a hydrophilic polymer is hydrosol and a cross-linked hydrosol is hydrogel. Both,
hydrogel and hydrosol can be reversibly transformed by altering functional groups and ionic concentration
in the polymeric structure as well as temperature of water. Hydrogels formulated in the presence of air,
nitrogen or carbon dioxide are known as porous hydrogels.

Certain hydrogels known as physiologically responsive hydrogels show drastic changes in their swelling
behaviour towards the changes in external environmental factors like temperature, pH, ionic strength and
electromagnetic radiations.

Hydrogel forming natural polymers include polysaccharides (starch, agarose, alginate etc..) collagen and
gelatin, whereas synthetic polymers that form hydrogels are prepared by employing chemical
polymerization methods.

Swelling of Hydrogels

Hydrogels are generally characterized by the following.

1. Swelling thermodynamics i.e., the capacity to absorb liquids.

2.Swelling kinetics i.e., the rate of absorbance of liquid into the polymer structure.

3. Wet strength i.e., their mechanical property in their hydrated state.

Hydrophilic polymers when placed in water or any aqueous solvents swell due to the presence of positive
and negative forces acting upon their chains.

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Polymers in CDDS

Fig. Structure of Hydrogel

For non-ionic polymers, the main driving force for swelling will be polymer-solvent interactions. When
these polymers interact with aqueous solvents, the ionic content of polymer increases and hence strong
osmotic and electrostatic forces gets generated within the structure. Now the ionic content within the
structure increases more than that in the solvent hence resulting in osmosis by which water enters the
polymer structure until the concentration of ions inside the hydrogel and in the surrounding solution
becomes equal. Certain amount of polymer also diffuses into water to balance its ionic content with the
surrounding solution. Now the polymer chains carrying ions gets positively or negatively charged and the
oppositely charged ions align in polymer chains and repel the similarly charged ions. Thereby generating
more space to accumulate extra water in the hydrogel.

Factors affecting swelling of Hydrogels:

Factors affecting swelling of hydrogels include cross-linking ratio, structure of the polymer as well as
environmental factors. Cross-linking ratio which is the ratio of moles of cross-linking agent to the moles of
polymer repeating units, is an important factor that effects the swelling of hydrogels. Cross-linking ratio is
directly proportional to the moles of cross-linking agent. Therefore lower cross-linking ratio indicates low
concentration of cross-linking agent, loose network and hence more swelling of the polymer when
compared to hydrogels with higher cross- linking ratios

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Polymers in CDDS

Swelling of hydrogels largely depends upon the chemical structure of the polymer. Polymers containing
hydrophobic groups usually collapse in the presence of water hence swell to a very low extent when
compared to polymers with hydrophilic groups. Hydrophilic groups absorb high proportions of water and
swell to a large extent.

Fig. : Hydrogels

Swelling of environmentally sensitive hydrogels can be affected by their respective stimuli. For instance
swelling of ionic strength, pH sensitive and temperature sensitive hydrogels can be affected by changes in
tonic strength, pH as well as temperature changes respectively.

Table: Hydrogel swelling and hydrosol solubility

Environmental Hydrogel/ hydrosol Effect on Effect on

factor hydrogels hydrosol
High temperature Inverse thermoresponsive Shrink Insoluble
Direct thermoresponsive Swell Soluble
Low temperature Inverse thermoresponsive Swell Soluble
Direct thermoresponsive Shrink Insoluble
High pH Cationic polymer Shrink Coil
Anionic polymer Swell Extend
Low pH Cationic polymer Swell Extend
Anionic polymer Shrink Coil
Low non- solvent More sensitive polymer Swell -
concentration
Less sensitive polymer Swell -

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Polymers in CDDS

Medium non solvent More sensitive polymer Shrink -

concentration
High non solvent Less sensitive polymer Shrink -
concentration

STRUCTURE AND PHYSICAL PROPERTIES OF HYDROGELS

The fundamental building block of a hydrogel is the water-soluble monomer. Many different monomers
can be used, ranging from hydrophilic vinyl-type monomers to sugars and amino acids. The latter two are
obtained from natural sources already in polymeric form. The monomer is then polymerized, either by
nature, as in the polysaccharides and proteins, or by a synthetic process. The crosslinking of the polymer to
form the hydrogel network may be done either during the polymerization, obtaining the hydrogel directly,
or after the water-soluble polymer has already been formed (see below). In addition to the general chemical
characteristics of the parent monomers, the resulting network is characterized by the average distance
between crosslinks (usually expressed in molecular weight as M.). which has a strong effect on its
properties.

A. THERMODYNAMICS AND SWELLING BEHAVIOR

In the dry state, hydrogels (often called xerogels when dry) are generally rather hard, with properties
ranging from “leathery” to “glassy.” However, when the material is placed in an aqueous medium, water is
imbibed, and the gel swells to an equilibrium defined by the point at which the swelling pressure is balanced
by the retractive force of the network.

The swelling pressure is the result of the difference in water activity inside and outside the polymer, and is
analogous to an osmotic pressure. Unlike osmotic pressure, the swelling pressure is not a colligative
property because, owing to the cross-linked structure of the polymer, there is really only one molecule in
“solution.” The final water content depends on the hydrophilicity of the polymer and the degree of
crosslinking, and can range up to well over 90%.

B. SURFACE PROPERTIES AND BIOCOMPATIBILITY

High interest in the use of hydrogels as biomaterials has led to intense study of their surface properties.
The importance of surface properties to biocompatibility can hardly be overstated; it is the interface
between the material and the biological environment where the interactions occur. Biocompatibility in its
most frequently used sense means the ability of the body to tolerate the material without unacceptable

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histological consequences for an extended period of time. For controlled drug delivery applications, the
importance of bio- compatibility depends on the site of administration and varies in proportion to the
lifetime of the device. For short-term delivery, e.g., oral dosage forms, biocompatibility is hardly an issue,
and the major concern is overt toxicity. For transdermal devices, irritation is a major concern, and may limit
useful service life to less than could be achieved by technology alone. However, toleration of transdermal
device may have little to do with the surface properties of the polymer, and may, in any given instance, be
related to the active agent, added penetration enhancers, etc. For a subdermal implant designed to release
drug over several months, biocompatibility is proportionally more important, although the requirements are
still probably less rigorous than for a permanent device in a critical area, such as a heart valve.

Unlike a crystalline solid, a hydrogel presents a diffuse surface with a more or less gradual transition
between the bulk gel and the surrounding bulk water. An important feature of the hydrogel surface is the
extremely high mobility of the polymer chains. This chain mobility allows the surface to adapt to its
environment. For example, poly(2-hydroxyethyl methacrylate) has two side chains: one terminated with a
methyl group, the other with a hydroxyl. Contact angle measurements by Holly and Refojo” showed that
the polymer surface appears hydrophobic when measured in air, but hydrophilic when measured in water.
The accepted explanation for this is that the side chains can rotate up or down to minimize the interfacial
energy. Thus the methyl group rotates to the surface when the polymer is placed in a hydrophobic
environment, and the hydroxyl group can extend outward when placed in a hydrophilic medium. The fact
that a hydrogel can be either hydrophilic or hydrophobic would seem to suggest an enhanced potential for
interaction with the components of the biological environment. However, in a survey of protein adsorption
measurements by Horbett, the observed trend was that hydrogels tended to adsorb less protein than the
(mostly hydrophobic) controls. Horbett suggests that in the absence of any strong binding sites on the
polymer, the high chain mobility may actually reduce the chance of forming a multipoint attachment.

C. WATER IN HYDROGELS

The condition of water in hydrogels is a subject of some controversy, with somewhat contradictory results
reported in the literature. The discussion usually centres on “free” versus “bound” water. Since the
distinction is not always clear, the states of water are often described in terms of the observable
freezing/melting behaviour. Studies on poly(glycerol methacrylate) by Yasuda et al. Utilizing DSC, NMR,
and permeability measurements showed only two kinds of water based on DSC measurements: a plot of
the enthalpy of fusion of water in the gel vs. Hydration yielded a straight line with slope equal to the heat
of fusion of pure water and an x-intercept corresponding a nonmelting water fraction of 0.36 (g water/g dry
polymer). However, their permeability measurements suggested the existence of an intermediate state of

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water in the gel. While the melting transition of water appeared at a volume fraction of 0.29 (by DSC and
NMR), the hydraulic permeability of the gel did not become measurable until the water volume fraction
reached 0.43. The authors were cautious in their interpretation of their results, stating: “These observations
suggest that water in swollen polymers is different from free water, no distinct state of water can yet be
assigned to it. Water seems to change gradually during increasing interaction with polymer molecules.

ADVANTAGES OF POLYMER USED IN CONTROLLED RELEASE

PREPARATION

1. Effective therapies while eliminating the potential for both under and over dosing
2. Maintenance of drug level within a desired range.
3. Optimal use of drug
4. Decrease incidence and/or intensity of adverse effect and toxicity.
5. Controlled rate and site of release.
6. Improved patient compliance
7. Reduce dosing frequency
8. More consistent prolonged therapeutic effect.
9. A greater selectivity of pharmacological activity.

DISADVANTAGES OF POLYMER USED IN CONTROLLED RELEASE

PREPARATION

1. Increase variability among units.

2. Toxicity due to dose dumping.
3. Undesirable by product of degradation.
4. More rapid development of tolerance.
5. Need for additional patient education and counselling.
6. The chances of patient discomfort form the delivery device.
7. Increase cost.

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CLASSIFICATION OF POLYMERS

Polymers are classified in a number of ways as described below.

(1) Classification based on source of availability (origin)

(2) Classification based upon structure.

(3) Classification based upon molecular forces.

(4) Classification based upon mode of synthesis (polymerization)

(5) Classification based upon the nature of monomers

(6) Classification based upon biostability

(A) BASED ON SOURCE OF AVAILABILITY (ORIGIN):

They are classified as :

a) Natural polymers

b) Synthetic polymers

c) Semi-synthetic polymers

NATURAL POLYMER:

These are also called biopolymers and possess the property of being biodegradable i.e., get converted to
simple biomolecules after a certain period of time of upon action by other substances present in the body.
These are natural in origin i.e., obtained from plants, animals, etc.

➢ Polysaccharides:
Plant origin- e.g. Starch, pectin

Microbial origin- e.g. xanthan gum

Marine origin- e.g. Alginates

➢ Proteins:
Animal origin- e.g. Gelatin, albumin, keratin

Plant origin- e.g. Zein

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SYNTHETIC POLYMERS:

Synthetic polymers are polymers which humans can artificially create/synthesize in a lab. These are
commercially produced by industries for human necessities. Some commonly produced polymers which
we use day to day are Polyethylene (a mass-produced plastic which we use in packaging) or Nylon Fibres
(commonly used in our clothes, fishing nets etc.)

SEMI-SYNTHETIC POLYMERS:

Semi-Synthetic polymers are polymers obtained by making modification in natural polymers artificially
in a lab. These polymers formed by chemical reaction (in a controlled environment) and are of
commercial importance. For example cellulose is naturally occurring polymers, cellulose on acetylation
with acetic anhydride in the presence of sulphuric acid forms cellulose diacetate polymers. It is used in
making thread and materials like films glasses etc. Vulcanized rubber is also a example of semisynthetic
polymers used in making tyres etc. Gun cotton which is cellulose nitrate used in making explosive.

(B) BASED ON THE STRUCTURE:

On the basis of structure of polymers these can be classified as

a) Linear polymers

b) Branched chain polymers

c) Cross linked polymers

LINEAR POLYMERS:

These are polymers in which monomeric units are linked together to form linear chain. These linear
polymers are well packed and therefore have high densities, high tensile (pulling) strength and high
melting points. Some common example of linear polymers are polyethylene nylon, polyester, PVC, PAN
etc.

Figure: linear polymer

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BRANCH CHAIN POLYMERS:

As the title describes, the structure of these polymers is like branches originating at random points from a
single linear chain. Monomers join together to form a long straight chain with some branched chains of
different lengths. As a result of these branches, the polymers are not closely packed together. They are of
low density having low melting points. Low-density polyethene (LDPE) used in plastic bags and general
purpose containers is a common example. Some common examples are low density polythene, glycogen,
starch etc. (Amylopectin).

Figure: Branched chain polymer

CROSSLINKED POLYMER:

In this type of polymers, monomers are linked together to form a three-dimensional network. The
monomers contain strong covalent bonds as they are composed of bi-functional and tri-functional in
nature. These polymers are brittle and hard because of network structure. Ex:- Bakelite (used in electrical
insulators), Melamine etc.

Figure: cross-linked polymer

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(C) CLASSIFICATION BASED UPON MOLECULAR FORCES:

Intramolecular forces are the forces that hold atoms together within a molecule. In Polymers, strong
covalent bonds join atoms to each other in individual polymer molecules. Intermolecular forces (between
the molecules) attract polymer molecules towards each other.

Depending upon the intermolecular forces, the polymers have been classified into four type.

a)Elastomers

b)Fibres

c)Thermoplastics

d)Thermosetting polymers

ELASTOMERS:

The polymers that have elastic character like rubber (a material that can return to its original shape after
stretching is said to be elastic) are called elastomers. In elastomers the polymers chains are held together
by weak intermolecular forces. Because of the presence of weak forces, the polymers can be easily stretched
by applying small stress and regains their original shape when the stress is removed. The most important
example of elastomers is natural rubber.

FIBRES:

These are the polymers which have strong intermolecular forces between the chain. These forces are either
hydrogen bonds or dipole-dipole interaction. Because of strong forces, the chains are closely packed giving
them high tensile strength and less elasticity. Therefore, these polymers have sharp melting points. These
polymers are long, thin and thread like and can be woven in fabric. Therefore, these are used for making
fibres. For example : Nylon 66, Dacron, silk etc.

THERMOPLASTICS:

These are the polymers which can be easily softened repeatedly when heated and hardened when cooled
with little change in their properties. The intermolecular forces in these polymers are intermediate between
those of elastomers and fibres. There is no cross linking between the chain. The softening occurs as the
polymer chain move more and more freely because of absence of cross link. When heated, they melt and
form a fluid which can be moulded into any desired shapes and then cooled to get the desired product.

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Example: Polythene, polystyrene, PVC, Teflon etc.

THERMOSETTING POLYMERS:

These are the polymers which undergo permanent change on heating. They become hard and infusible on
heating. They are generally prepared from low molecular mass semifluid substances. When heated they get
highly cross linked to form hard infusible and insoluble products. The cross links hold the molecule in place
so that heating does not allow them to move freely. Therefore a thermosetting plastic is cross linked and is
permanently rigid.

Example : Bakelite, melamine formaldehyde etc.

(D) BASED UPON MODE OF SYNTHESIS (POLYMERIZATION)

a) Addition polymers

b) Condensation polymers

ADDITION POLYMER:

These type of polymers are formed by the repeated addition of monomer molecules. The polymer is formed
by polymerization of monomers with double or triple bonds (unsaturated compounds). In this process, there
is no elimination of small molecules like water or alcohol etc.

For example: Alkane polymer

(Ethene) nCH2=CH2 —› -(CH2-CH2)n (polyethene)

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CONDENSATION POLYMERS:

A polymer formed by the condensation of two or more than two monomers with the elimination of simple
molecule like water, ammonia HCl, alcohol etc. is called condensation polymers.

For example: Nylon 66 made by adipic acid and hexamethylene diamine. It leads to loss of
hydrogenmolecules.

(E) CLASSIFICATION BASED UPON THE NATURE OF MONOMER:

On the basis of nature of monomer polymer are of two type

a) Homopolymers

b) Copolymers

HOMOPOLYMERS:

These polymers contain only one kind of repeating unit in their structure. The proper identification of this
unit is especially needed when the polymer is a condensation polymer.

E.g.: Polybutadiene, polyethylene, poly (ethylene terephthalate), etc.

COPOLYMERS:

These polymer formed from two or more different monomers is called copolymer or mixed polymer.

Example: nylon 66

Alternating Copolymers:

These polymers contain two or more kinds of repeating units arranged alternately.

E.g.: Poly(styrene-alt-butadiene).

(–A–B–A–B–A–B–A–B–A–B–A–B–)

Random copolymer:

A random copolymer is a polymer composed of two or more different monomers in no specific sequence.
The arrangement of monomer units occurs randomly along the polymer chain, resulting in a diverse
chemical structure. (–A–A–A–B–A–B–A–B–B–B–B–A–A–)

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Block copolymers:

Block polymers are those in which different blocks of identical monomer units alternate with each other as

(– A – A – A – A – B – B – B – B – A – A – A – A – B – B – B – B –)

Graft polymer:

Graft polymers are those in which homopolymer branches of one monomer units are grafted on the
homopolymer chains of another monomer units as:

Figure: Graft polymer

(F) BASED ON BIOSTABILITY:

Two types:

a)Biodegradable

b)Non- biodegradable

BIODEGRADABLE :

e.g. Polyester

NON- BIODEGRADABLE :

e.g. Ethyl cellulose

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CHARACTERISTICS OF POLYMERS

PROPERTIES OF POLYMERS:

1. Molecular Weight:

Polymers are described using average molecular weight as these may possess molecules with different
molecular weights. This property along with molecular weight distribution of polymers is important as it
in determining other properties of the polymer such as its mechanical strength. The molecular weight of
polymers can be determined by using osmometry, light scattering, viscometry and gel permeation
chromatography. Osmometry utilizes the principle of osmotic pressure which is capable of measuring high
molecular weight characteristics to polymers, and employs a semipermeable membrane that allows only
solvent molecules to pass through and not the high molecular weight polymers. Therefore, the activity of
the solvent in the two regions across the semipermeable membrane establishes an osmotic pressure gradient
that can be related to the molecular weight of polymer. Scattering of light by dilute solutions of polymers
can be used to estimate average molecular weight of polymers. Osmometry and light scattering absolute
methods of determining molecular weight i.e., indicates the molecular weight directly. Viscometry is a
relative method of measuring molecular weight of the polymers wherein the viscosity of solution of a
polymer of unknown molecular weight is compared with the viscosity of a solution containing a polymer
of known molecular weight (standard solution). Therefore the equipment and the method used for
determination require calibration using standard samples. This determination is based on the principle that
with increase in molecular weight of the viscosity of its solution also increases. Even gel permeation
chromatography is a relative method for measuring molecular weights and molecular weight distribution
of polymers. The procedure uses column containing porous beads with varying pore sizes, which helps in
differential elution of polymers having varying molecular weight when dilute solutions of polymers with
varying molecular weights are passed through the column, high molecular weight polymer solutions will
come out of the column first, followed by others in descending order of their molecular weights.

2. Polymer Hydrophobicity:

Polymers present in the DDS interact with water when the DDS is exposed to the aqueous environment in
the body. Based on the type of interaction. Are classified as hydrophobic polymers, hydro philic polymers,
water-soluble polymers and hydrogels.

(a) Hydrophobic Polymers:

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Polymers which do not allow water to permeate through and absorb less than 5% by weight of water when
placed in an aqueous environment are called hydrophobic polymers. The parameters which determine this
property include chain stiffness, high degree of crystallinity of polymer and presence of highly hydrophobic
groups in the polymer.

(b) Hydrophilic Polymers:

Polymers which absorb more than 5% by weight of water when placed in an aqueous environment are
called hydrophilic polymers. The parameters which determine this property include chain flexibility,
presence of groups like carboxyl, amino etc., and absence of crystalline nature.

(c) Water-soluble Polymers:

These polymers dissolve freely in water despite their high molecular weight.

E.g.: acid), poly(vinyl alcohol) etc.

(d) Hydrogels:

Polymers which absorb excessive amounts of water but do not dissolve in it due to the presence of covalent
cross-linkages in their structure are called hydrogels.

3. Glass Transition Temperature:

Amorphous polymers remain in a glassy state characterized hardness, brittleness and stiffness at low
temperatures. When the temperature is raised above a certain point known as glass transition temperature
T. (characteristic to a polymer), they g show a change in their properties like refractive index, hardness,
permeability etc. This temperature is also known as second-order transition and depends upon chain
stiffness and intermolecular forces.

4. Crystallinity:

Polymers show crystallinity when they show an ordered arrangement of molecules. This property imparts
to the polymer, thereby reducing its permeability to water.

5.Thermal Analysis:

Polymers can be analysed using techniques like thermogravimetric analysis (TGA), differential scanning
calorimetry (DSC) and thermomechanical analysis (TMA) to determine various properties.

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TGA involves measurement of weight of a sample while it is being heated. Thus, the loss of weight of
sample can be estimated. It helps in estimating the thermal stability of the polymer wherein the temperature
at which weight loss begins is regarded as the upper limit of thermal stability.

DSC can be used for estimation of glass transition temperature, heats of fusion, heats of crystallization and
crystalline melting points of polymers. TMA can be used to measure softening temperatures and transition
of polymers from glassy to rubbery state.

6.Mechanical Properties:

Polymers can be characterized for their mechanical properties by plotting stress-strain graphs using suitable
methods. In these methods, stretching force (stress) is applied to the polymer sample and the resultant
elongation (strain) due to the force is determined. These are plotted as graphs to estimate the mechanical
properties of the polymer.

CRITERIA FOLLOWED IN POLYMER SELECTION:

Polymer chosen as potential drug carrier must exhibit properties as listed below

1.The polymer must be soluble and easy to synthesized, it must have a finite molecular weight and narrow
distribution.

2. It should provide drug attachment sites for possibility of incorporation of drug polymer linkages.

3.The polymers should be compatible with the biological environment, that is nontoxic, non antigenic, non-
immunogenic, non-thrombogenic, non-allergenic, non-carcinogenic and non-provocative, in any other
respect

4. It should be biodegradable or be eliminated from the organization after the fulfilment of its function.

5. It should be easily sterilisable.

6. It should be free of leachable impurities.

7. It should be reproducibly synthesizable.

8. It should be versatile, and have wide range of physical, mechanical and chemical properties.

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MECHANISM OF POLYMERIZATION:

Polymerization occurs in three steps, i.e.

• Initiation
• Propagation
• Termination

Initiation :

Chain initiation is the foremost step in the polymerization process. An active centre is generated in this
process to begin polymerization. All the monomers are not liable for the initiation process.

• One or two radicals are created from the initiating molecules in the first step.
• Radicals are transferred from the initiating molecules to the monomer units in the second step.

Figure: chain Initiation step

Propagation :

A polymer spends most of its time expanding its chain length or propagating. After initiation of free radical,
it attacks another monomer subunit. It uses one of the pi bond electrons to form a stable bond with another
carbon atom. The other electron returns to the second carbon atom, turning the whole molecule into a
radical.

After initiation, the chain propagates until no monomer is left or termination starts.

Figure: chain propagation step

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Termination

Chain termination is the final step in the polymerization process. Termination occurs in different stages. If
longer chains are expected, the initiator concentration should be less; otherwise, many short chains will
form.

Figure: chain termination step

GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER

3 different mechanisms:

• Diffusion
• Degradation
• Swelling (water penetration)

Any of these mechanisms may occur

Diffusion :

In this system the drug release rate depends on diffusion rate of the from the membrane. It is the major
process of absorption. Basically diffusion is movement of drug molecule from higher to lower
concentration. It is directly proportional to concentration gradient across the membrane. No energy is
required in this process. The rate controlling step is diffusion. Diffusion follows zero order kinetics.

A) Reservoir (encapsulated) –
In membrane-controlled reservoir devices, the drug is contained in a core, which is
surrounded by a polymer membrane, and it is released by diffusion through this rate-
controlling membrane. Coating or micro encapsulation used for polymer coating. It is
governed by Ficks law of diffusion.
e.g. Poly(N-vinyl pyrrolidone), Poly(ethylene-co-vinyl acetate).

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B) Matrix (monolithic) –
The drug is homogeneously distributed in polymeric matrix. In these devices, the drug is released either
by passing through the pores or between polymer chains, and these are the processes that control the
release rate.
Matrix diffusion is governed by Higuchi equation.
E.g. Fatty material, hydrophilic gums, natural polymer (guar gum, tragacanth), synthetic
(polyacrylamide), semi synthetic polymer (HPMC, CMC)

DEGRADATION:

The drug is initially dispersed in a polymer and it is released when the polymer starts eroding and degrading.

The four most commonly used biodegradable polymers in drug delivery systems are poly(lactic acid),
poly(lactic- co-glycolic acid), polyanhydrides, esters), and poly(phosphoesters).

It can occur by 2 mechanism:

Hydrolytic degradation - polymer bonds react with water molecules, break up, and produce new chain ends

Enzymatic mechanisms - adsorption of enzymes on the polymer surface, followed by hydro-

peroxidation/hydrolysis of the bonds

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WATER PENETRATION ( SWELLING):

This type of systems are initially dry and when placed in body, absorb water or other fluid and it swells.

Swelling increases aq. solvent content within the formulation as well as the polymer mesh size, enabling
the drug to diffuse through the swollen network into external environment.

E.g. (N-isopro-pylacrylamide), Ethylene-vinyl alcohol.

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APPLICATIONS OF POLYMERS:

1.Polymers in Mucoadhesive Delivery:

The new generation mucoadhesive polymers for buccal drug delivery with advantages such as; increase in
the residence time of the polymer, penetration enhancement, site-specific adhesion, and enzymatic
inhibition, site-specific mucoadhesive polymers will undoubtedly be utilized for the buccal delivery of a
wide variety of therapeutic compounds. The class of polymers has enormous potential for the delivery of
therapeutic macromolecules

2. Ocular Drug Delivery System :

It allows prolonged contact of the drug with the corneal surface of the eye. An example of ODDS is
pilocarpine in the treatment of glaucoma. In this, mucoadhesive polymers are used as barriers to control
the drug release. E.g. Polyacrylic acid, Copolymers of acetate vinyl, and ethyl.

3. Oral drug delivery systems

4. Formulation of Matrix tablets.

5. Formulation of Nanoparticles.

6. Micelles for cancer therapeutics.

7. Transdermal Drug Delivery System :

TDDS is defined as, self-contained, self-discrete dosage forms, which when applied to the intact skin,
deliver the drug at a controlled rate to the systemic circulation. In this, polymer matrix plays a major role.
It releases the drug from the device to the skin.

8.. Drug Delivery of Various Contraceptives and Hormones :

It consists of a drug saturated liquid medium encapsulated in a polymeric layer which controls the
concentration and release of drugs into the bloodstream. E.g. Medoxy progesterone acetate, Progestasert,
Duromine, etc.

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9. Drug Delivery and the Treatment of Diabetes:

Here the polymer will act as a barrier between the bloodstream and insulin. E.g. Polyacrylamide or N, N-
Dimethyl amino ethylmetha acrylate.

10.. In solid dosage form, polymer like CMC is used. Cellulose acetate thylate used as enteric coating
material

11. Used in coating, to mask taste.

12. Natural gums are used as thickening agent ( cellulose derivatives)

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 65|

MALARIA

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