Natural and Biodegradable polymer.

1. SEMINAR ON
BIODEGRADABLE POLYMER
&
NATURAL POLYMER
FACILITATEDBY:
mr. prakash goudanavar
DEPT OF PHARMACEUTICS
N.E.T. Pharmacy College
PRESENTEDBY:
Dharmendra chaudhary
DEPT OF PHARMACEUTICS
N.E.T. Pharmacy College

2.  Polymers are very large molecules consisting of
many repeating units and formed by a process
known as polymerization, which links together
small molecules known as monomers.
 They are also known as macromolecules.
 The monomers are linked together by covalent
bonds.
 Monomers can be linked together in various ways
to give
1. Linear
2. Branched
3. Cross linked polymers

3.  Linear and branched polymers are also
known as thermoplastic polymers becauses
they can flow when heated thus can be
fabricated by the application of heat and
pressure they are also soluble in certain
solvents.
 Crossed linked polymers are known as
thermosetting polymers as they don’t flow
when heat or pressure is applied and hence
cannot be fabricated by application of heat
and pressure since all the polymer chains are
inter connected by covalent cross links , they
cannot dissolve and only swell to the extent
allowed by crossed linked density

4.  Biodegradable polymers are polymer that
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 has been completed.
 They are broken down into biologically
acceptable molecules that are
metabolized and removed from the body
via normal metabolic pathways.

5.  The drug depleted delivery systms used could
cause toxicological rxns if retained in the body &
removal of this from body was difficult and surgical
methods had to be adopted to remove it.
 These type of polymers have wide range of
applications because in non biodegradable
polymers, the drug release is controlled by
diffusion through polymer phase which depends on
molecular weight, solubility of drug & polymer
permeability. Therefore drugs which are poorly soluble
like proteins having a high a high molecular weights are
not suitable candidates for delivery system involving non-
biodegradable matrices systems as these can aggregate
in the matrix and may lead to clogging of pores for
diffusion.

6.  It should be inert to tissues and compatible with
environment.
 It should be non- toxic and non –antigenic.
 It should be biodegradable and should be
eliminated from body after its function.
 It should be soluble and easy to synthesis.
 It should have good mechanical strength, tensile
strength, hydrophilicity & crystallarity.

7. 1.Synthetic polymers
a) Polyamides e.g.:Polyamino acids, Polypeptides
b) Polyesters e.g.: Poly(glycolide), Poly(D,L-lactide)
Poly(D,L-lactide-co-glycolide)
Poly(E-caprolactone)
Poly(dioxanone), Poly(hydroxybutyrate)
c) Polyanhydride
d) Polyorthoester
e)Polyphosphazene
f)Polyphosphoester e.g.: Polyphosphate,
Polyphosphonate, Polyphosphate

8. 2. Natural polymers
a)Polysaccharides e.g.: Dextran, Chitosan
Alginate, Starch
Hyaluronic acid
b)Polypeptides, Proteins e.g.: Collagen, Gelatin,
Fibrinogen , Albumin
Bovine serum albumin (BSA)
Human serum albumin (HSA)

9. BIODEGRADATION
ENZYMATIC
DEGRADATION COMBINATION
HYDROLYSIS
BULK EROSION SURFACE EROSION

10. Degradation primarily is the process of chain clevage leading to
reduction in molecular weight
Erosion is the sum of all the processes leading to loss of mass from
polymer matrix
A polymer can erode without degradation and a polymer can degrade
completely without being eroded.
Polymer DEGRADATION
BULK EROSION SURFACE EROSION
rate of water penetration exceeds the
rate at which polymer is converted into
water soluble materials
rate of water penetration is slower than the
rate at which polymer is converted into
water soluble materials

11. Polymer Degradation by Erosion

12. Steps in polymer degradation:
• In first Phase water penetrates the bulk of the device &
preferentially attacks the chemical bonds in the
amorphous phase leading to conversion of long chain
polymer into short water soluble fragments & due to this
there is change in physical property of polymer matrix.
• In second Phase there is rapid loss of polymer
mass due to enzymatic attack which leads to
fragmentation.
Polymer erosion:
Term polymer erosion is generally used to
signify conversion of an initially water insoluble material
to water soluble

13. Type 1 erosion: evident with water soluble polymers
cross linked to form a 3D structure.
This network remains insoluble till the cross links are
intact but when placed in aqueous environment
erosion occurs by cleavage of cross links or water
soluble back bone following which the matrix begins
to swell & dissolves
Type 2 erosion:occurs with polymers that were earlier
water insoluble but converted to water soluble forms
by hydrolysis, ionization or protonation of a pendant
group
Type 3 erosion: occurs in polymers that were of high
molecular weight but transformed to small, water
soluble molecules via hydrolytic cleavage of labile
bonds in the polymer

14. Factors affecting polymer degradation:
1. Hydrophilicity:  hydrophilicity  water  rate
2. Tg:  Tg   water uptake  rate
3. Crystallinity:  crystallinity   water uptake  rate
4. Temperature:  temp  rate
5. Acid or base: rate
6.  porosity (inc. surface area)  rate
7. Presence of drug (may both promote and perclude polymer
hydrolysis)

15.  poly (glycolide), poly(lactide), and various
copolymers of poly(lactide-co-glycolide) are
ubiquitous choice because of their proven safety
and lack of toxicity, their wide range of
physicochemical properties, and their flexibility to
be processed into a variety of physical dosage
forms.
 prepared by anionic ring-opening reaction of
highly purified glycolide and lactide monomers, the
cyclic dimers of glycolic acid and lactic acid,
respectively.

16.  Homopolymers of polylactide are semicrystaline hence
water transport (uptake) to polymer is low and so the
degradation rate of polymer is relatively slow (18-24
mnth).
 In contrast Poly(D,L-lactide) PLA is amorphous and
degrade somewhat faster(12-16 mnth).
 Polyglycolide despite being semicrystaline degrade
faster(2-4mnth) even compared to amorphous PLA bcoz
of greater hydrophilicity of glycolide over lactide.
 Poly(D,L-lactide-co-glycolide) PLG amorphous if
glycolide content is 0-70%.
 Poly(L-lactide-co-glycolide) amorphous when glycolide
content is 25-70%.
 Most rapid degradation (2 mnth) in PLG is copolymer
with 50% glycolide content.

17. Biodegradation:
Occurs in 2 steps
1. Random hydrolytic cleavage of ester linkage
leading to redn in mol.wt.
2. Onset of wt.loss and a change in rate of
chain scission.
Drug release:
Combination of initial leaching/diffusion
followed by bioerosion of matrix.
Uses:
In microparticulate drug delivery.

18. Adv. Of PCL as biodegradable CDDS
1. Slow degradtion rate, suitable for long term(1yr)
delivery system
2. Biodegradibility can be increased by
copolymerization.
3. High permiability to large no. of drugs.
4. Non-toxic profile.
5. Ability to form compatible blends with many
other polymers.

19.  Monomer Synthesized by oxidation of cyclohexane
with perchloric acid .
 Can be blended with cellulose propionate, cellulose
acetate butyrate, polylactide, PLG.
Biodegradation:
 Random hydrolytic chain scission of the ester linkage
 In 2nd phase, shows decreased rate of chain scission
& weight loss due to diffusion & phagocytosis

20.  Specially for surface eroding dosage forms.
 The anhydride linkages of these polymers are, in general,
more hydrolytically labile than the polyester bond. In order to
achieve a surface-eroding mechanism, polymers are
generally prepared from very hydrophobic monomers in
order to minimize water penetration into the bulk of the
device. By doing this, hydrolysis of the labile anhydride
linkages would be restricted to the outer exposed surfaces
of the polymer device.
 Prepared from dicarboxylic acid like adipic acid, sebacic
acid(SA), fumaric acid(FA).
 Degrade only from the surface to maximize control in a
heterogeneous manner over the release process
without requiring any additives .
 Degrade more rapidly in basic media then in acidic media.

21.  Have acid labile linkage in their backbone which
facilitates manipulation of hydrolysis rate by means of
acidic or basic excipients.
 Are acid sensitive and are stable in base.
 Used to fabricate contraceptive steroid bearing
bioerodible implants.
 Prepared by transesterifiacation of diol and co-hydroxy
butyric acid.
 Also prepared by addition of polyols to diketene
acetals.
 Polymer erosion can be accelerated by using diols
bearing pendent carboxylic groups(eg.9,10-
dihydroxystearic acid ) as comonomers.

22.  Contain a long chain backbone of alternating
phosphorus and nitrogen atoms.
 Degrade into endogenous N & P compounds hence
ideal biodegradable polymers
 synthesis by rxn of poly(dichlorophosphazene)with
organic nucleophiles such as alkoxides,aryloxides, or
amines.
 Can be hydrohilic or hydrophobic.
 Polymer prodrugs have been prepared in which
the drug entity is covalently attached to the
polyphosphazene.
 Polyphosphazenes have been studied for the
delivery of proteins, naproxen and colchicine, as
well as in periodontal treatments.

23.  Generally referred as polyphosphates(P-O-C),
polyphosphonates (P-C) or polyphosphites
depending on nature of side chain attached to
phosphorus.
 Disadvntage: Cost of synthesis and apparent
hydrolytic instability.
 used as microspheres for delivery of drugs like
lidocaine, placitaxel, cisplatin and as a gel for
lidocaine, doxorubicin.

24. Also known as biopolymers these have a few advantages like:
• They are derived from natural source
• Easily available
• Relatively cheap
• Qualified for a number of chemical modifications
 Natural polymers can be proteins and polysaccharides in
chemical origin
 The natural polymers are subjected to a number of chemical
modifications so as to increase the biodegradability. So
generally labile functional groups are added to the polymer to
enhance the biodegradability.

25.  Structural protein which occurs in animal tissues as aligned fibers
in skin connective tissue and in bone.
Advantages:
 Easy to isolate & purify
 Biocompatible & non toxic
 Well established physiochemical, structural & immunological
properties
 Easy to process
Disadvantages :
 Variability in drug release kinetics,
 In vivo swelling and poor dimensional stability.
 Low mechanical strength and elasticity in vivo
 Chances of triggering antigenic response
 Tissue irritation

26.  These limitations can be overcome to a certain
extent by using collagen shields. These shields
are prepared from intact porcine scleral tissues.
• Collagen is most widely used in case of ocular
dosage forms. On application the tear fluid hydrates
the shield & it starts to dissolve. This leads to its
softening & subsequent compliance to the corneal
surface
 Soluble succinylated collagen insert of gentamycin
used as an ocular drug delivery system.
 Formaldehyde treated and chrome treated films of
medroxyprogestsrone for sustained release of the
hormone etc.

27.  It is a major plasma protein component. It is mostly used to
design particulate drug delivery system.
 advantage include their bioavailability into natural products,
easy availability, absence of toxicity & antigenicity.
 Albumin microspheres have been employed to deliver many
drugs including insulin, 1- norgestrel, haematoporphyrin,
sulphadiazine, prednisolone, 5- fluorouracil, doxorubicin &
mitomysin.
 Basically albumin microspheres have been exploited for
chemotherapy as with them high local drug administration can
be achieved for a relatively longer time period.
 Typically the release pattern of drugs from albumin
microspheres is biphasic. The initial burst release is followed
by a comparatively slower first order release.

28. Gelatin:
It is a heterogeneous product obtained by irreversible
hydrolytic extraction of treated animal collagen. This partial
hydrolysis converts the tough fibrous collagen into an unoriented
water soluble protein.
Gelatin micropellets can be prepared oral controlled delivery of
drugs.
Gelatin has been employed as a matrix and as a coating
material in drug delivery systems.
Advantages:
Easy availability
 Low antigen profile
Poor binding to drug molecule
Low temperature preparation technique that reduces the

29. Fibrinogen:
Fibrinogen is a soluable plasma protein
having a molecular weight of 340,000.
 Fibrinogen microspheres can be
prepared by emulsification technique
followed by thermal denaturation.
Drugs like doxorubicin 5- fluro urasil, &
adriamysin have been delivered with
fibrinogen microspheres.

30. Chitin & Chitosin:
Chitin is a linear polycationic polymer of N-
acetyl-D –glucosamine. It is highly insoluble in
common solvents & has close resemblance to
cellulose by having similar solubility profile & low
chemical reactivity.
The principle industrial source of chitin is shells of
shrimp lobsters & crab.
Chitosin is a principle derivative of chitin & is
obtained by alkaline deacetylation . They are
distinguished by their solubility profile in dil. Aq.
Acid solns.

31. Pharmaceutical & biomedical applications are:
• Show antacid & anti ulcer activity
• Show wound healing properties
• Show haemostatic & spermicidal property
• Presence of reactive functional groups & cationic
character opens up possibilities for their
applications in controlled drug delivery
• Good biodegradability, biocompatibility, & non
toxic
• Has gel forming ability at low ph.
• Chitosin has been used as a direct tableting
agent.

32. • Addition of chitosin to conventional excipients
decreases the angle of repose and therby
increases the fluidity of powder mixtures
• It has been used as a diluent binder lubricant
and potential disintegrant due to its water
uptake property
• Ulcerogenic drugs like aspirin can be
effectively administered with chitosin as the
latter has gel forming property at low ph and
also has anti ulcer and antacid property
• Gastric mucosal injury associated with
diclofenac sodium can be reduced with chitosin
• Oral mucoadesive tablets based on chitosin
also show immense application potential

33. • As it has gel forming property at low ph It can be
used for oral sustained drug delivery system
• Mucoadesive chitosin coated liposomes could
improve the oral absorption of insulin.
• Chitosin has inherent antitumour activity thus
chitosin microspheres bearing neoplastic agents
are therapeutically promising carriers for treatment
of cancer.
• The film forming capacity of the chitosin can be
employed for development of contact lenses.
• It can be employed in ocular bandage lenses
used as protective devices for acutely and
chronically traumatized eyes.

34. These are hydrophilic carbohydrates obtained
from various species of brown sea weed by the
use of alkali.
• They can be easily fabricated into particulate
carriers.
• They are particularly beneficial as carriers of
peptides and other sensitive drugs since
particulate carriers can be easily prepared in
aqueous solutions at room temperature.
• Alginate microspheres have been effectively
used for oral delivery of vaccines.

35.  It is a polymer of glucose.
 Obtained by action of bacteriunm Leuconostoc
mesenteroides on sucrose.
 The crude high mol wt dextran is formed is
hydrolyzed and fractionated to yeild dextran of
desired mol wt.
 Polymers with mol.wt. below 90,000 rarely show
immunogenic rxn.
 Used in the form of gel for colonic delivery of drugs