Polymer in pharmaceutics by prof. TARiQUE khan sir. AACP Akkalkuwa

CONTENTS
 INTRODUCTION TO POLYMERS
 CLASSIFICATION OF POLYMERS
 GENERAL MECHANISM OF DRUG RELEASE
 APPLICATION IN CONVENTIONAL DOSGAE FORMS
 APPLICATIONS IN CONTROLLED DRUG DELIVERY
 BIODEGRADABLE POLYMERS
 NATURAL POLYMERS
 REFERENCESS
7th Sept. 2010 KLECOP, Nipani
1

INTRODUCTION
A polymer is a very large molecule in which one
or two small units is repeated over and over again
The small repeating units are known as
monomers
Imagine that a monomer can be represented by
the letter A. Then a polymer made of that
monomer would have the structure:
-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-
A-A-A
2

In another kind of polymer, two different monomers
might be involved
If the letters A and B represent those monomers, then
the polymer could be represented as:
-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-
B-A
A polymer with two different monomers is known as
a copolymer.
3

Chemistry of the polymers
 Polymers are organic, chain molecules
 They can, vary from a few hundreds to
thousands of atoms long.
 There are three classes of polymers that we
will consider:-
a. Thermo-plastic - Flexible linear chains
b. Thermosetting - Rigid 3-D network
c. Elastomeric - Linear cross-linked chains
4

THERMOPLASTICS
 In simple thermoplastic polymers, the chains are bound
to each other by weaker Van der Waal’s forces and
mechanical entanglement.
 Therefore, the chains are relatively strong, but it is
relatively easy to slide and rotate the chains over each
other.
5

ELASTOMERS
 Common elastomers are made from highly coiled,
linear polymer chains.
 In their natural condition, elastomers behave in a similar
manner to thermoplastics (viscoelastic)
– i.e. applying a force causes the chains to uncoil and
stretch, but they also slide past each other causing
permanent deformation.
 This can be prevented by cross-linking the polymer
chains
6

 Polymers can be represented by
 – 3-D solid models
 – 3-D space models
 – 2-D models
7

MOLECULAR STRUCTURE
 The mechanical properties are also governed by the
structure of the polymer chains.
 They can be:
Linear Network (3D)
Branched
Cross-linked
8

POLYMER MOLECULES
 Before we discuss how the polymer chain molecules are
formed, we need to cover some definitions:
 The ethylene monomer looks like
 The polyethylene molecule looks like:
9

 Polyethylene is built up from repeat units or mers.
 Ethylene has an unsaturated bond. (the double bond
can be broken to form two single bonds)
 The functionality of a repeat unit is the number of sites
at which new molecules can be attached.
10

MOLECULAR WEIGHT
 When polymers are fabricated, there will always be a
distribution of chain lengths.
 The properties of polymers depend heavily on the
molecule length.
 There are two ways to calculate the average molecular
weight:
1 Number Average Molecular Weight
2. Weight Average Molecular Weight
11

 Number Average Molecular Weight
Mn= Σ Xi Mi
Where, xi = number of chains in the ith weight range
Mi = the middle of the ith weight range
 Weight Average Molecular Weight
Mw = Σ Wi Mi
Where, wi = weight fraction of chains in the ith range
Mi = the middle of the ith weight range
12

MOLECULAR SHAPE
 The mechanical properties of a polymer are dictated in
part by the shape of the chain.
 Although we often represent polymer chains as being
straight,
 They rarely are.
13

Contd…
 The carbon – carbon bonds in simple polymers form
angles of 109º
14

15

POLYMER CRYSTALLINITY
 Thermoplastic polymers go through a series of changes
with changes in temperature. (Similar to ceramic
glasses)
 In their solid form they can be semi-crystalline or
amorphous (glassy).
16

17

CRYSTALLINE THERMOPLASTIC
 The ability of a polymer to crystallize is affected by:
1. Complexity of the chain: Crystallization is easiest for
simple polymers (e.g. polyethylene) and harder for
complex polymers (e.g. with large side groups,
branches, etc.)
2. Cooling rate: Slow cooling allows more time for the
chains to align
3. Annealing: Heating to just below the melting
temperature can allow chains to align and form crystals
4. Degree of Polymerization: It is harder to crystallize
longer chains
5. Deformation: Slow deformation between Tg and Tm
can straighten the chains allowing them to get closer
together.
18

CLASSIFICATION POLYMERS:
 ON BASIS OF INTERACTION WITH WATER:
 Non-biodegradable hydrophobic Polymers
E.g. polyvinyl chloride, polyethylene vinyl acetate
 Soluble Polymers E.g. HPMC, PEG
 Hydrogels E.g. Polyvinyl pyrrolidine
 BASED ON POLYMERISATION METHOD:
 Addition Polymers E.g. Alkane Polymers
 Condensation polymers E.g. Polysterene and Polyamide
 Rearrangement polymers
 BASED ON POLYMERIZATION MECHANISM:
 Chain Polymerization
 Step growth Polymerization
19

Contd….
 BASED ON CHEMICAL STRUCTURE:
 Activated C-C Polymer
 Polyamides, polyurethanes
 Polyesters, polycarbonates
 Polyacetals, Polyketals, Polyorthoesters
 Inorganic polymers
 Natural polymers
 BASED ON OCCURRENCE:
 Natural polymers E.g. 1. Proteins-collagen, keratin,
albumin, 2. carbohydrates- starch, cellulose
 Synthetic polymers E.g. Polyesters, polyamides
20

Contd….
 BASED ON BIO-STABILITY:
 Bio-degradable
 Non Bio-degradable
21

CHARACTERISTICS OF AN IDEAL POLYMER
 Should be versatile and possess a wide range of
mechanical, physical, chemical properties
 Should be non-toxic and have good mechanical strength
and should be easily administered
 Should be inexpensive
 Should be easy to fabricate
 Should be inert to host tissue and compatible with
environment
22

CRITERIA FOLLOWED IN POLYMER SELECTION
 The polymer should be soluble and easy to synthesis
 It should have finite molecular weight
 It should be compatible with biological environment
 It should be biodegradable
 It should provide good drug polymer linkage
23

GENERAL MECHANISM OF DRUG RELEASE FROM
POLYMER
 There are three primary mechanisms by which active
agents can be released from a delivery system: namely,
 Diffusion, degradation, and swelling followed by
diffusion
 Any or all of these mechanisms may occur in a given
release system
 Diffusion occurs when a drug or other active agent
passes through the polymer that forms the controlled-release
device. The diffusion can occur on a
macroscopic scale as through pores in the polymer
matrix or on a molecular level, by passing between
polymer chains
24

Drug release from typical matrix
release system
25

 For the reservoir systems the drug delivery rate can
remain fairly constant.
 In this design, a reservoir whether solid drug, dilute
solution, or highly concentrated drug solution within a
polymer matrix is surrounded by a film or membrane of
a rate-controlling material.
 The only structure effectively limiting the release of the
drug is the polymer layer surrounding the reservoir.
 This polymer coating is uniform and of a nonchanging
thickness, the diffusion rate of the active agent can be
kept fairly stable throughout the lifetime of the delivery
system. The system shown in Figure a is representative
of an implantable or oral reservoir delivery system,
whereas the system shown in b.
26


Drug delivery from typical
reservoir devices: (a)
implantable or oral
systems, and (b)
transdermal systems.
27


28

ENVIRONMENTALLY RESPONSIVE SYSTEM
 It is also possible for a drug delivery system to be
designed so that it is incapable of releasing its agent or
agents until it is placed in an appropriate biological
environment.
 Controlled release systems are initially dry and, when
placed in the body, will absorb water or other body fluids
and swell,
 The swelling increases the aqueous solvent content
within the formulation as well as the polymer mesh size,
enabling the drug to diffuse through the swollen network
into the external environment.
29

 Examples of these types of devices are shown in
Figures a and b for reservoir and matrix systems.
 Most of the materials used in swelling-controlled release
systems are based on hydrogels, which are polymers
that will swell without dissolving when placed in water or
other biological fluids. These hydrogels can absorb a
great deal of fluid and, at equilibrium, typically comprise
60–90% fluid and only 10–30% polymer.
30

 Drug delivery from (a) reservoir
and (b) matrix swelling-controlled
release systems.
31

Stimulus Hydrogel Mechanism
pH Acidic or basic
hydrogel
Change in pH-swelling-
release of
drug
Ionic strength Ionic hydrogel Change in ionic
strength change in
concentration of ions
inside gel change in
swelling release of
drug
Chemical species Hydrogel
Electron-donating
containing
compounds formation
electron-accepting
of charge/transfer
complex change in
groups
swelling release of
drug 32

Enzyme-substrate
Hydrogel
containing
immobilized
enzymes
Substrate present
enzymatic conversion
product changes swelling
of gel release of drug
Magnetic Magnetic particles
dispersed in
alginate
microshperes
Applied magnetic field
change in pores in gel
change in swelling release
of drug
Thermal Thermoresponsive
hrydrogel poly(N-isopro-pylacrylamide
Change in temperature
change in polymer-polymer
and water-polymer
interactions change in
swelling release of drug
33

APPLICATIONS
 The pharmaceutical applications of polymers range
from their use as binders in tablets
 Viscosity and flow controlling agents in liquids,
suspensions and emulsions
 Polymers are also used as film coatings to disguise the
unpleasant taste of a drug, to enhance drug stability and
to modify drug release characteristics.
07/09/2010 KLECOP, Nipani
34

Applications in
Conventional Dosage Forms
 Tablets :
- As binders
- To mask unpleasant taste
- For enteric coated tablets
 Liquids :
- Viscosity enhancers
- For controlling the flow
 Semisolids :
- In the gel preparation
- In ointments
 In transdermal Patches
35

Applications In Controlled
Drug Delivery
 Reservoir Systems
- Ocusert System
- Progestasert System
- Reservoir Designed Transdermal Patches
 Matrix Systems
 Swelling Controlled Release Systems
 Biodegradable Systems
 Osmotically controlled Drug Delivery
36

BIO DEGARADABLE POLYMERS
37

BIO DEGRADABLE POLYMER
 Biodegradable polymers can be classified in two:
 Natural biodegradable polymer
 Synthetic biodegradable polymer
 Synthetic biodegradable polymer are preferred more than the
natural biodegradable polymer because they are free of
immunogenicity & their physicochemical properties are more
predictable &reproducible
38

FACTORS AFFECTING BIODEGRADATION
OF POLYMERS
 PHYSICAL FACTORS
 Shape & size
 Variation of diffusion coefficient
 Mechanical stresses
 CHEMICAL FACTORS
 Chemical structure & composition
 Presence of ionic group
 Distribution of repeat units in multimers
 configuration structure
 Molecular weight
 Morphology
 Presence of low molecular weight compounds
39

CONTD
 Processing condition
 Annealing
 Site of implantation
 Sterilization process
 PHYSICOCHEMICAL FACTORS
 Ion exchange
 Ionic strength
 pH
40

ADVANTAGES OF BIODEGRADABLE
POLYMERS IN DRUG DELEVERY
 Localized delivery of drug
 Sustained delivery of drug
 Stabilization of drug
 Decrease in dosing frequency
 Reduce side effects
 Improved patient compliance
 Controllable degradation rate
41

ROLE OF POLYMER IN DRUG DELIVERY
The polymer can protect the drug from the physiological
environment & hence improve its stability in vivo.
Most biodegradable polymer are designed to degrade within the
body as a result of hydrolysis of polymer chain into biologically
acceptable & progressively small compounds.
TYPES OF POLYMER DRUG DELIVERY SYSTEM:
MICRO PARTICLES: These have been used to deliver
therapeutic agents like doxycycline.
NANO PARTICLES: delivery drugs like doxorubicin, cyclosporine,
paclitaxel, 5- fluorouracil etc
42

 POLYMERIC MICELLES: used to deliver therapeutic agents.
 HYDRO GELS: these are currently studies as controlled
release carriers of proteins & peptides.
 POLYMER MORPHOLOGY:
The polymer matrix can be formulated as either
micro/nano-spheres, gel, film or an extruded shape.
The shape of polymer can be important in drug release
kinetics.
43

Application
 For specific site drug delivery- anti tumour agent
 Polymer system for gene therapy
 Bio degradable polymer for ocular, non- viral DNA, tissue
engineering, vascular, orthopaedic, skin adhesive &
surgical glues.
 Bio degradable drug system for therapeutic agents such
as anti tumor, antipsychotic agent, anti-inflammatory
agent and biomacro molecules such as proteins, peptides
and nucleic acids
44

BIO DEGRADABLE POLYMERS FOR ADVANCE
DRUG DELIVERY
 Polymers play an vital role in both conventional as well as
novel drug delivery. Among them , the use of bio degradable
polymer has been success fully carried out.
 Early studies on the use of biodegradable suture
demonstrated that these polymers were non- toxic &
biodegradable.
 By incorporating drug into biodegradable polymer whether
natural or synthetic, dosage forms that release the drug in
predesigned manner over prolong time
45

DRUG RELEASE MECHANISM
 The release of drugs from the erodible polymers occurs
basically by three mechanisms,
I. The drug is attached to the polymeric backbone by a
labile bond, this bond has a higher reactivity toward
hydrolysis than the polymer reactivity to break down.
II. The drug is in the core surrounded by a biodegradable
rate controlling membrane. This is a reservoir type device
that provides erodibility to eliminate surgical removal of
the drug-depleted device.
III. a homogeneously dispersed drug in the biodegradable
polymer. The drug is released by erosion, diffusion, or a
combination of both.
46

Schematic representation of drug release mechanisms In mechanism 1, drug is released
by hydrolysis of polymeric bond. In mechanism 2, drug release is controlled by
biodegradable membrane. In mechanism 3, drug is released by erosion, diffusion, or a
combination of both
47

POLYMER EROSION MECHANISM
 The term 'biodegradation' is limited to the description of
chemical processes (chemical changes that alter either
the molecular weight or solubility of the polymer)
 ‘Bioerosion' may be restricted to refer to physical
processes that result in weight loss of a polymer device.
 The erosion of polymers basically takes place by two
methods:-
1. Chemical erosion
2. Physical erosion
48

CHEMICAL EROSION
 There are three general chemical mechanisms that cause
bioerosion
1. The degradation of water-soluble macromolecules that are
crosslinked to form three-dimensional network.
As long as crosslinks remain intact, the network is intact
and is insoluble.
Degradation in these systems can occur either at
crosslinks to form soluble backbone polymeric chains (type
IA) or at the main chain to form water-soluble fragments
(type IB). Generally, degradation of type IA polymers
provide high molecular weight, water-soluble fragments,
while degradation of type IB polymers provide low
molecular weight, water soluble oligomers and monomers
49

50

2. The dissolution of water-insoluble macromolecules
with side groups that are converted to water-soluble
polymers as a result of ionization, protonation or
hydrolysis of the groups. With this mechanism the
polymer does not degrade and its molecular weight
remains essentially unchanged. E.g. cellulose acetate
3. The degradation of insoluble polymers with labile
bonds. Hydrolysis of labile bonds causes scission of
the polymer backbone, thereby forming low molecular
weight, water-soluble molecules. E.g. poly (lactic
acid), poly (glycolic acid)
The three mechanisms described are not mutually
exclusive; combinations of them can occur. 7th Sept. 2010 KLECOP, Nipani
51

PHYSICAL EROSION
 The physical erosion mechanisms can be
characterized as heterogeneous or homogeneous.
 In heterogeneous erosion, also called as surface
erosion, the polymer erodes only at the surface, and
maintains its physical integrity as it degrades. As a
result drug kinetics are predictable, and zero order
release kinetics can be obtained by applying the
appropriate geometry. Crystalline regions exclude
water. Therefore highly crystalline polymers tend to
undergo heterogeneous erosion. E.g
polyanhydrides
52

 Homogeneous erosion, means the hydrolysis
occurs at even rate throughout the polymeric
matrix. Generally these polymers tend to be
more hydrophilic than those exhibiting surface
erosion. As a result, water penetrates the
polymeric matrix and increases the rate of
diffusion. In homogeneous erosion, there is loss
of integrity of the polymer matrix. E.g poly lactic
acid
53

 Natural polymers
 Polymers are very common in nature
 some of the most widespread naturally occurring substances are
polymers Starch and cellulose are examples
 Green plants have the ability to take the simple sugar known as
glucose and make very long chains containing many glucose units
These long chains are molecules of starch or cellulose
If we assign the symbol G to stand for a glucose molecule, then starch
or cellulose can be represented as:
 -G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-
54

NATURAL POLYMERS
 Natural polymers remains the primary choice of
formulator because
- They are natural products of living organism
- Readily available
- Relatively inexpensive
- Capable of chemical modification
 Moreover, it satisfies most of the ideal requirements of
polymers.
 But the only and major difficulty is the batch- to-batch
reproducibility and purity of the sample.
55

 Examples :
1) Proteins :
- Collagen : Found from animal tissue.
Used in absorbable sutures, sponge
wound dressing, as drug delivery vehicles
- Albumin : Obtained by fabrication of
blood from healthy donor.
Used as carriers in nanocapsules &
microspheres
- Gelatin : A natural water soluble polymer
Used in capsule shells and also as coating
material in microencapsulation.
56

2) Polysaccharides :
- Starch : Usually derivatised by introducing acrylic
groups before manufactured int microspheres.
Also used as binders.
- Cellulose :
Naturally occuring linear polysaccharide. It
is insoluble in water but solubility can be obtained by
substituting -OH group.
Na-CMC is used as thickner, suspending agent, and
film formers.
3) DNA & RNA :
They are the structural unit of our body. DNA
is the blueprint that determines everything of our body.
57

CURRENTLY AVAILABLE POLYMERS FOR
CONTROLLED RELEASE
 Diffusion controlled systems
 Solvent activated systems
 Chemically controlled systems
 Magnetically controlled systems
58

DIFFUSION CONTROLLED SYSTEM
 Reservoir type
 Shape : spherical, cylindrical, disk-like
 Core : powdered or liquid forms
 Properties of the drug and the polymer : diffusion rate
and release rate into the bloodstream
 Problems : removal of the system, accidental rupture
 Matrix type
 Uniform distribution and uniform release rate
 No danger of drug dumping
59

SOLVENT ACTIVATED SYSTEM
 Osmotically controlled system
 Semipermeable membrane
 Osmotic pressure decrease concentration gradient
 Inward movement of fluid : out of the device through
a small orifice
 Swelling controlled system
 Hydrophilic macromolecules cross-linked to form a
three-dimensional network
 Permeability for solute at a controlled rate as the
polymer swells
60

CHEMICALLY CONTROLLED SYSTEMS
 Pendant-chain system
 Drug : chemically linked to the backbone
 Chemical hydrolysis or enzymatic cleavage
 Linked directly or via a spacer group
 Bioerodable or biodegradable system
 Drug : uniformly dispersed
 Slow released as the polymer disintegrates
 No removal from the body
 Irrespective of solubility of drug in water
61

MAGNETICALLY CONTROLLED SYSTEMS
 Cancer chemotherapy
 Selective targeting of antitumor agents
 Minimizing toxicity
 Magnetically responsive drug carrier systems
 Albumin and magnetic microspheres
 High efficiency for in vivo targeting
 Controllable release of drug at the microvascular
level
62

RECENTLY DEVELOPED MARKETED FORMULATIONS
 Medisorb
• Microencapsulation by PLA, PGA, PLGA
• Drug release : week to one year
 Alzamer
• Bioerodible polymer : release at a controlled rate
• Chronic disease, contraception, topical therapy
63

USE OF FEW POLYMERS IN DRUG DELIVERY
 Poly(L-lactic acid) for release of progesterone, estradiol,
dexamethasone
 Copolymer of gluconic acid and –ethyl-L-glutamte as bioerodible
monolithic device
 PLA, PGA, PLGA for parenteral administration of polypeptide
 Sustained release (weeks or months)
Orahesive® : sodium carboxymethyl cellulose, Pectin,
gelatin
 Orabase ® : blend in a polymethylene/mineral oil base
64

REFERENCES
 Novel drug delivery systems – Y.W.Chien –
Dekker 50
 Bio–adhesive drug delivery system –
Dekker 98
 Encyclopedia of controlled drug delivery
systems.
 www.google.com
65

ANY QUERIES?
66

T H A N K Y O
U
67
Cell No: 00919742431000
E-mail:bknanjwade@yahoo.co.in

Polymer in pharmaceutics by prof. TARiQUE khan sir. AACP Akkalkuwa

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (20)

Similar to Polymer in pharmaceutics by prof. TARiQUE khan sir. AACP Akkalkuwa

Similar to Polymer in pharmaceutics by prof. TARiQUE khan sir. AACP Akkalkuwa (20)

Recently uploaded

Recently uploaded (20)

Polymer in pharmaceutics by prof. TARiQUE khan sir. AACP Akkalkuwa