Polymers Used In Controlled Drug Delivery System

1. Made By:
HEENA PARVEN
Assistant Professor

2. CHARACHTERISTICS FOR
IDEAL POLMERS:
Chemically inert & free from leaching impurity.
Good mechanical strength .
Non-toxic & compatible with enviornment .
Easily sterilized .
Easy and inexpensive .
Acceptable shelf life.

3.  POLYMER ACTIVITY:

4. POLYMER ACTION:

5. GENERAL MECHANISM OF DRUG
RELEASE FROM POLYMER:
 DIFFUSION:
Diffusion occurs when the drug passes from the
polymer matrix into the external environment.
The combinations of polymer matrices and
bioactive agents chosen must allow for the drug to
diffuse through the pores or macromolecular structure
of the polymer upon introduction of the delivery
system into the biological environment without
inducing any change in the polymer itself.

6.  DEGRADATION:
 Biodegradable polymer degrades within the body as a result
of natural biological processes, eliminating the need to
remove a drug delivery system after release of the active
agent.
 Degrade as a result of hydrolysis of the polymer chains into
biologically acceptable and progressively smaller
compounds.
 Some degradable polymers the poly anhydrides and poly
orthoesters, the degradation occurs only at the surface of
the polymer, resulting in a release rate that is proportional
to the surface area of the drug delivery system.

7. Various routes for degradation
of polymers:

8. Factors affecting
biodegradation of polymers:

9. SWELLING :
 They 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.

10. EROSION :
 TYPE 1 (erosion):
It involves hydrolysis of hydrogels and these are useful in the
controlled release of macromolecules entangled within their
network structure .
 TYPE 2 (erosion):
It involves solubilization of water-insoluble polymers by
reactions involving groups from polymer backbone .
Polymer that solubilizes by ionization of -COOH grp and the
utilisation of those systems.
 TYPE 3 (erosion):
It involves cleavage of hydrolytically labile bonds. 4 systems are
included:
1.Diffusion of drug from bioerodible membrane , 2. utilizes
macromolecules , 3.utilizes monolithic devices ,4. utilizes drugs
chemically bound to a bioerodible polymer.

11. Non Biodegradable hydrophobic polymers :
 Eg: polyvinyl chloride
 Soluble polymers :
 Eg:HPMC , PEG
 Hydro gels :
 Eg: polyvinyl Pyrrolidine

12. NON BIODEGRADABLE
HYDROPHOBIC POLYMERS:
The polymers are not biodegradable in-vivo in
systemic circulation .
These have hydro phobicity .
 SOLUBLE POLYMERS:
They are hydrophillic synthetic polymers .
These are not degradable in-vivo.
Polymers are low mol.wt than the renal threshold
in systemic circulation.

13. HYDROGELS:
A Lightly cross – linked water soluble polymer forms a hydrogels .
It absorbs water and swells but do not dissolves in aq. media .
Degree of cross – linking determines its swelling and expansion .
They are biostable and bioerodible , erosion occurs by hydrolytic
cleavage of cross – linking.
EG: 1.MEEP can be converted into hydrogels by exposing to gamma
radiation.
[MEEP- bis (methoxy ethoxy methoxy) phosphazene.]
2. Alginate hydrogels
3. Polyelectrolyte hydrogels

14. 2. BASED ON
POLYMERISATION
METHOD:
 ADDITION POLYMERS :
The polymer have the same mol.formula as the monomer.
Prepared by polymerisation of monomers bearing one or more double/triple
bonds or by the ring opening of cyclic structures.
Eg : Alkane polymers
 CONDENSATION POLYMERS :
The polymers are connected by successive reaction functional groups .
They are linear molecules that are semicrystalline and thermoplastic in nature
.
 Eg: polystyerene , polyamides

15. 3. BASED ON
POLYMERISATION
MECHANISM:
Chain polymerisation:
The high molecular mass molecules formed by monomers.
It involves 3 steps: initiation , propagation , termination.
a) INITIATION:
When free radical catalyst reacts with double bonded
carbon monomers , begins the polymer chain.
b) PROPAGATION :
It is the repetitive operation with the physical chain of
polymer is formed. The double bond of monomer is
opened up when monomer reacted to reactive polymer
chain.
c) TERMINATION:
It occurs when another free rdical, over from original
splitting of organic peroxide , melts end of growing
chain. This reaction produces a complete polymer chain.

16. STEP GROWTH
POLYMERISATION:
This method produces polymers of lower
molecular wt. than the chain reaction & requires
higher temp. to occur .
It involves 2 different types of disfunctional
monomers or end groups that react with one
another , forming a chain.

17. 4. BASED ON CHEMICAL
STRUCTURE:
Activated C-C polymer
Inorganic polymers
Natural polymers

18. 5. BASED ON OCCURRENCE :
NATURAL POLYMERS :
These may be proteins and poly sacchrides in chemical origin
.
They have improved degradation profile.
EG : a - PROTEINS : collagen , keratin , albumin
 Non toxic , biocompatible
 Anti genicity
 Low binding to drug
b- POLY SACCHRIDES : cellulose , dextran , insulin,
hyaluranic acid , starch, gum.

19. SYNTHETIC POLYMERS:
It is refered as plastic such as polyethylene & nylon .Synthetic is used over
natural as variation in its composition from sources. It is prefered as it
contains less microbial contamination compared to natural.
 It is synthesised by 2 methods:
o Addition polymerisation
o Step reaction polymerisation
EG: 1. –Cellulose nitrate – first synthetic polymer formed by cotton react
with nitric acid also known as gun cotton. It soon replaced gun
powder . Also used to make polymer for making safety glass.
 Some more examples:
A- Polyester : poly lactic acid , poly glycolic acid
B – Poly amide: poly amino acid , poly imino carbonate
C- Others: poly hydroxyl butyrate , poly anhydride , polyurethanes , poly
phosphonates

20. 6. BASED ON
BIOAVAILABILITY :
Biodegradable :
The least bio available polymer which are degrable
enzymatically by hydrolytic cleavage of linkages .These are
synthesised linking of monomers .
EG : poly ortho ester , poly phosphonates ,polyacetals .
Non bio – degradable :
They are bio available polymer which is not degradale
in the systemic circulation . Thus have more chances
of causing toxicity and incompatibility.
EG : a- cellulose derivatives – HPMC, cellulose acetate
b – silicons : poly dimethyl siloxane, colloidal silica
c – Other– poly vinyl pyrrolidine , poloxamine

21. 7. ENVIORNMENTALLY
RESPONSIVE POLYMERS:
 . [* also known as SMART Polymers or STIMULI Responsive Polymers .]
 PHASE sensitive polymers :
Phase sensitive smart polymers are mainly used to prepare biocompatible
formulations of proteins for controlled delivery in biologically active and
confarmationally stable form.
EG: a water insoluble biodegradable polymer such as poly(D,L-lactide) and poly(D,L-
lactide-co-glycoide) dissolve in pharmaceutically accepted solvent to which a drug is
added forming a solution .
After injecting the formulation into the body the water miscible organic solvent dissipates
and water penetrates into the organic phase. This causes the phase separation and
precipitation of the polymer forming a depot at the site of injection .
 PH sensitive polymers :
pH sensitive polymers are poly electrolytes that contains acid(carboxylic
or sulphonic ) or basic(ammonium salts) functional groups in their structure,
so in response to change in ph they can accept or release a protons .These
groups of smart polymers change its solubility by changing their electrical
charge of the polymer molecule.

22. PHASE
SENSITIVEPOLYMERS:

23. Cont….
LIGHT sensitive polymers :
It is attractive because it enables one to change the
geometry and dipole moment of photo-switching
molecules causing macroscopic variations of molecularly
organized structures by small perturbations. These changes
can effect final properties such as wettability , permeability,
charge, color, binding and alignment.
Thermosensitive Polymers :
The aqueous solutions of these polymers undergo sol-
gel transition in response to temperature changes and
deliver the drug in vivo

24.  SMART POLYMERS :
 ALSO KNOWN AS stimulli responsive or
enviornmentally responsive polymers .
 Smart polymers are materials composed of polymers that
respond in a dramatic way to very slight changes in their
environment.
 Environmental stimuli include salt, UV irradiation,
temperature, pH or concentration , chemicals, light,
magnetic or electricfield, ionic factors, biological
molecules, solvent exchange etc.

25.  SMART POLYMERS
EXAMPLES:
STIMULLI POLYMERS
PH Dendrimers , chitosan ,eudragit S , L-
100 , carbopol
TEMPERATURE Prolastin , poloxamer
PHOTO SENSITIVE PEG , Polylactic acid
PHASE SENSITIVE poly(D,L-lactide) ; poly(D,L-lactide-co-
glycoide)
MAGNETIC FIELD PNIPAAm hydrogels containing
ferromagnetic material PNIPAAm co-
acrylamide
ELECTRIC SIGNAL IONS Sodium alginate(Ca 2+) ; chitosan (mg
2+)
ORGANIC SOLVENT Eudragit S- 100

26.  ACTION OF SMART
POLYMERS:

27. 8. POLYMERS EMPLOYED IN
DRUG DELIVERY DEVICES:
Polymeric Phospholipids:
The phospholipids molecules easily form polymer on irridiation with u.v .
On incorporation with liposomes into bilayers , they increase their
precipitation and leakage .
Polyethyleneimine:
It is used in water purification , ore extraction , and in shampoos . It is a
vector for gene transfer .
 Polyamidoamine:
It is used for synthesis of dendrimers .Dendrimers also furnish a soluble
nanoscopic matrix to link targetting molecules or other moities for
enhancing transfection .
 Polyethylene Glycol:
PEG mol.wt upto10 KD are linear . Higher mol.wt are branching .They
are non-biodegradable .It is prefered due to excellent solubility ,low
toxicity,low antigenicity, and immunogenicity.

28. 9. BASED ON THERMAL
REPONSE:
THERMOPLASTIC :
Polymers with linear molecules are known as
thermoplastic . These are substances that soften
upon heating & can be remolded & recycled .
They can be semi-crystalline or amorphous .
THERMOSETTING :
They do not soften upon heating & can be moulded
or recycled .
They must be remachined used used as fillers .

29. 10. BASED ON LINEAR
STRUCTURE:
LINEAR and BRANCHED :
Monomers are linked to produce linear polymers . It may be
thermoplastic materials as they flow on heating and thereby
permitting fabrication by applying heat and pressure.
EG: PEG
 CROSS-LINKED:
They are also known as thermosetting materials . They do not flow
when heated . They are interconnected by cross links . They do not
dissolve but swells to the extent allowed by cross link density.
EG : Hydrogels

30. 11. BASED ON APPLICATION AND
PHYSICAL PROPERTIES:
RUBBER:
It has the capability of being deformed easily into varies
shaped . It can resist external pressure and temperature to an
extent of deformity.
PLASTICS :
Plastic polymeric materials that have capability of being
molded or shaped , by applying heat and pressure .it has low
density low electric conductivity , transparency.
EG: PVC
FIBRES:
It has the capability to form a network with drug to an extent so
as to form matrix structure to release the drug slowly.

31.  EXAMPLES:
 Poly (urethanes) :
For elasticity and coating .
• Poly (siloxanes ) :
Silicones for insulating capability .
• Poly ( methyl methacrylate ) :
For physical strength and transparency. It is compatibile to
human tissues and can be used create microfluidiclab-on-achip
devices.
• Poly (vinyl alcohol) :
For hydrophilicity and strength .Used for feminine
hygiene and adult incontinence pdts as a biodegradable plastic
backing sheet .
 Poly( vinyl pyrrolidone ) :
For suspension capability used as adhesives .

32. 12. BASED ON TACTICITY :
TACTICITY :
The spatial arrangement of monomers grp in chain . A
conformation of geometrical arrangement of atoms in the
polymeric chain . Isotactic and syndiotactic are semi-
crystalline.
ISOTACTIC :
In a configuration, when all the R grps lie on the same side of
the plane formed by the extented chain backbone.
SYNDIOTACTIC :
If the substituent groups regularly alternate from one side of
plane to the other side .
ATACTIC :
It is amorphous indicating absence of crystallinity .

33. 13. BASED ON CRYSTALLINITY:
CRYSTALLINITY :
Morphologically most polymers are semi – crystalline . It show a
high degree of ordered formed by folding and stacking of the
polymer chains .
 AMORPHOUS:
When it is compared with crystalline polymers are unorganised &
interwine with each other lacking a proper chain formation thus
making its strength temperature dependent .
EG : Poly sulfone , poly etherimide , polyethersulfone
SEMI CRYSTALLINE :
In it the molecules pack together in ordered regions ca crystallites
with in an amorphous matrix .It is arranged randomly and are
interwined.
CRYSTALLINE :
Crystalline molecules are arranged closely and in a discernible order .

34. 14. BASED ON STRUCTURE:
HOMOPOLYMERS:
It is the polymer which contains identical monomer units .
EG :
• Polyalkylenes
• Polyalkylnylenes
• Polyalkylnylynes
HETEROCHAIN POLMERS:
It is the polymers which contains 2 or more monomer
units in chain.
EG :
• C-O polmers
• C-S polmers
• C-N polymers

35. 15. MISC . APPROACHES FOR
POLYMERS:
 Polymers for colon targeting
• Azo polymers
• Poly sacchrides
 Polymers for site specific delivery in periodonitis
 Polymers for mucoadhesive site specific drug
delivery
 Dendrimers
 Polymers for particulate carriers
 Polymers for nano & micro particles

36. NOVEL MUCO ADHESIVE
POLYMERS:
 Bio adhesion can be defined as a phenomenon of
interfacial molecular attractive forces amongst the
surfaces of the biological substrate and the natural or
synthetic polymers, which allows the polymer to
adhere to the biological surface for an extended period
of time.
 Attraction and repulsion forces arise and, for a muco
adhesive to be successful, the attraction forces must
dominate. The mechanism of muco adhesion is
generally divided in two steps, the contact stage and
the consolidation stage :

37.  MECHANISM :

38. MUCO ADHESIVE
POLYMERS:
DRUG POLYMER ROUTE PURPOSE
Acyclovir Chitosan Ocular Slow release inc.
AUC
Methyl
prednisolone
Hyaluronic acid Ocular Slow release sustain
drug conc. in ear
fluid
Gentamicin DSM+LPC Nasal Inc. nasal
absorption
Insulin DSM+LPC Nasal Effective delivery
via nasal route
Cephradine ChitosanEC GI Prolong intestinal
absorption
Furosemide AD-MMS(PGEFs) GI Inc. bioavailability

39. Cont…..
Vancomycin PGEF coated
with eudragit – S
100
COLONIC Well absorbed
even without
absorption
enhancer
Insulin PGEF coated
with eudragit – S
100
COLONIC Absorbed only in
presence of
absorption
enhancer ,eg:
EDTA salt
Nerve growth
hormone
HYAFF Vaginal Inc. absorption as
compare to aq.
Sol of drug
Insulin HYAFF Vaginal Inc .absorptioas
compare to aq.
Sol of drugn

40. POLYMERS FOR
PERIODONITIS:
DRUG /SUSTAINED RELEASE
DELIVERY SYSTEM
POLYMER
Metronidazole bioerodible polymer
insert
Blends of cellulose acetate pthalate and
pluronic L101
Salicylic acid, caffeine tripelennamine
film
PEG+EC
Chlorhexide chitosan
Tetracycline films Poly (lactide-co- glycolide)

41. AZOPOLYMERS FOR COLON
TARGETING:
AZOPOLYMER DOSAGE
FORM
DRUG INVITROIN-
VIVO MODEL
COMMENTS
Copolymer of
styrene with 2-
hydroxy
methacrylate
Coating over
capsule
Vasopressin ,
insulin
Rats, dogs Show
biological
responseof
these peptide
hormone
Segmented
polyurethenes
Coating over
pellets
budesonide rat Bring about
healing in
induced colitis
Aromatic azo
bond
containing
urethane
analogs
Degradable
films
5-ASA INVITRO Film
degradation
Copolymer of
N-(2-hydroxy
propyl)methacr
Bioadhesive
polymer bound
to the drug
5-ASA Guinea pig fructose with
HPMA
copolymer

42. DENDRIMERS:
 Greek word “dendron”means tree like.
 Globular,highly branched polymers .
 3-D shape , size and mol.wt
 Construct via step wise procedure.
 Hyperbranched polymers:
• Prepared by a one step or single pot process
• posses greater mol.wt. distinction or polydispersity
trailored to posses uniform or discrete functionality and
posses tunable internal packaging densities,void
vol.,surface moities,mol.mass,solvent dependent size and
branching dimensions.
• Synthesis approaches: higher generation dendrimers

43. A. Convergent Approach
B. Divergent Approach
E.G: Polyamidoamine (PAMAM)dendrimers
 Dendrimer polycations for delivery of genes:
E.G: poly-4-vinyl pyridine
chitosan
poly[(2-dimethyl amino)ethyl metha crylate]

44. POLYMER FOR
NANOPARTICLES:-
1. NATURAL HYDROPHILLIC POLYMERS:-
A. PROTIENS:Gelatin,albumin,lutin,legumin,vecilin
B. POLYSACCHRIDES:Alginate,dextran,chitosan
2. SYNTHETIC HYDROPHOBIC POLYMER:-
A. PREPOLYMERISED:- Poly(ethly-caprolactone) (PECL)
• Poly(lactic acid)(PLA)
• Poly(lactids-co-glycolide)(PLGA)
• Poly styrene

45. B. POLYMERIZED IN PROCESS:-
 Poly(isobutyl cyanoacrylates)(PICA)
 Poly(butyl cyanoacrylate) (PBCA)
 Poly hexyl cyanoacrylate )PHCA)
 Polymethyl (methacrylate)(PMMA)
 Copolymer of amino alkyl methacrylate,methly
acrylate

46. Polymers for particulate carriers:
CARRIER TARGETS/DISEASE/THERAPY
1-PROTIENS:(antibodies;antibody
fragments)e.g:- collagen-specific
drug-toxin-cojugate
Injured sites of blood vessels
wall:tumour cells
lipoproteins Liver; cancer of ovaries & gonads
lectins Gen. carriers/recognition ligands
Dextrans(enz- drud-dextran
conjugate)
tumours

47. Deoxyribonucleic acid(lysosomatic
carrier)
Cancer cells
2-SYNTHETIC POLYMERS:-
Poly-4-lysine&Polyglutamic acid
cancer
Poly-4-aspartic acid (hydrolysable) Cancer
Polypeptide-mustard conjugates Lung tumor
HPMA/pyran copolymer Lysosomotropic carrier for cytotoxics

48. -HEENA PARVEEN