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A SEMINAR ON

BIODEGRADABLE POLYMERS

GUIDED BY
Mr. S. G. Bidkar
Department of pharmaceutics

Presented By
Mr. Shahaji jamadar
M.Pharm 1st sem (pharmaceutics)

AISSMS COLLEGE OF PHARMACY


PUNE
Date: 1.10.2009 1
CONTENTS
 Definition
 Ideal characteristics
 Advantages and Disadvantages
 Polymers erosion mechanism
 Polymers drug release mechanism
 Classification of polymers along with their
application
 Product based on biodegradable polymers
 References

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BIODEGRADABLE
POLYMERS
DEFINITION:
The natural ability of chemical
substance to be broken down into
less complex compounds having
fewer carbon atoms by body fluids
or enzymes or microorganism.
OR
It is defined as the breakdown
of polymer into its components
monomers or oligomers upon
IDEAL CHARACTERISTICS
OF BIODEGRADABLE
POLYMERS
 Minimal side effects after
introduction into body.
 In vivo degradation at well defined
rate.
 Degradation products should be
nontoxic and easily excreted.
 Free from any toxic endogenous
impurities or residual chemical.
 Should be inert in nature.
 Should have relative stability.
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ADVANTAGES OF
BIODEGRADABLE
POLYMERS
 Useful for delivery of synthetic drugs as
well as proteins and biotechnological
products .
 No need subsequent retrival of the
delivery.
 Better drug utilization and improved
patients compliance.
 Targeted specific part of body hence
reduce side effect.
 Provide controlled rate of drug release.

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DISADVANTEGES OF
BIODEGRADABLE
POLYMERS
 Difficult to formulate a biodegradable
system
 Carrier must be human friendly.
 Some polymers do not have detail
information about its
biodegradability, kinetic, stability
profile.

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POLYMERS EROSION
MECHANISM
 Bioerosion : physical process that
result in weight loss of polymer
devices.
Two types of erosion
1.chemical erosion
2.physical erosion

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Chemical erosion
 Mechanism 1
Type 1A] Degradation in these
system can occur either at cross links
to form soluble backbone polymeric
chains provide high molecular weight,
Type 2B] At the main chain to form
water soluble fragments. Provide low
molecular weight fragments.
 Mechanism 2
water insoluble macromolecule with
side groups converted in water soluble
polymer by ionization, protonation or
hydrolysis of groups.
 Mechanism 3
Degradation of insoluble polymers
with labile bonds .hydrolysis of labile
bond causes scisson of polymer
backbone.

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Polymers & their
chemical mechanism of
erosion
 Gelatin Type 1
 Collagen Type 1 & Type 2
 Polyanhydrides Type 3
 Polycaprolactone &
it’s copolymer
 Poly (ortho esters) Type 3
 Poly (lactic acids) Type 3
 Poly (glycolic acid) Type 3
 Poly (vinyl alcohol)
Type 3
Type 1

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Physical erosion

 Heterogeneous erosion
called surface erosion,
polymer erode only at
surface and maintain it’s
physical integrity.
 Homogenous erosion
called bulk erosion
hydrolysis occur at even
rate throughout the
polymer matrix.

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DRUG RELEASE MECHANISMS OF
BIODEGRADABLE POLYMERS
 In mechanism 1 the drug is
attached to polymer
backbone by labile bond,
shows higher reactivity to
breakdown.
 Mechanism 2 drug release
is controlled by
biodegradable membrane
surrounded by core
containing drug .
 Mechanism 3
homogeneously dispersed
drug in biodegradable
polymers released by
erosion diffusion or
combination of both.

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CLASSIFICATION OF
BIODEGRADABLE
POLYMERS.
Synthetic Natural

Lactide & glycolides. Collagen.

Polyanhydride Gelatin.

Poly-E-Caprolactone. Albumin.

Polyphosphazenes. Starch

Pseudo(amino acid) Dextran.

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SYNTHETIC BIODEGRADABLE
POLYMERS ALONG WITH THEIR
COPOLYMERS
1)Lactide & glycolides Poly [lactic acid] (PLA)
Poly [glycolic acid] (PGA)
Poly [ lactide-co-glycolic] (PLGA)

2)Polyanhydride Poly [carboxy-phenoxy- propane] Sebasic acid


(PCPP-SA)
Poly [terepthalic acid] Sebasic acid (PTA-SA)

3)Polyphosphaazenes Hydrophobic groups like fluoro alkoxy side group


aryl groups ,poly tetra fluoro ethylene.
Hydrophilic groups like short chain alkyl amino
side groups.
4)Poly-E-caprolactone Copolymer derived from poly ethylene glycol,
polystyrene.
Copolymer with lactide & glycolides

5)Pseudo (amino acid) Tyrosine derived poly (amino) carbonate

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POLYMERS AND THEIR
APPLICATION
Lactide & glycolides

 Considered as GRAS product by FDA


GRAS [Generally recognized as safe]

 Synthesis by ring opening melt


condensation of cyclic dimers such as
Lactide & glycolides.

 Degradation by homogenous erosion.

 Can be easily fabricated into


microspheres,implants and fibers 14
APPLICATIONS
 L-PLA are suitable for sustain release of
-Narcotic antagonist [naltrexone,naloxone] for
morphine dependence.
-anticancer agents
[cisplatin,cyclophosphamide]
-steroids [norethisterone]to prolong its effects.
 PLA and PGA are suitable for antimalarial drugs
[quinazolin]
 Poly DL-lactide co glycolides formulated with
various antibiotics
[ampicilline,polymixin,chloramphenicol]

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 Local anesthetics [lidocaine,xylocaine]
are formulated with homo and co-
polymers of lactide and glycolides.
 In formulation of veterinary products
[melatonin loaded system for sheep for
production of fur.
 Bioactive agents like polypeptides
[LHRH,calcitonin] and vaccine [antigen,
antibody] can given with this.
 co-polymers used formulate
biotechnology products.

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POLYANHYDRIDE
 Better biocompatibility with body tissue

 Rate of hydrolytic degradation at the


surface of the polymer system is faster
than the of rate of penetration into the
bulk of the polymers matrix hence use for
water liable drugs

 Polycondensation,dehydrochlorination and
dehydrative coupling synthesize this
polymers.

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APPLICATION
 CPP-SA used to formulate anticancer agents
[carmustine] –used in treatment of glioblastoma
multiforme,which is a type brain cancer.

 Angiotensin inhibitors formulate with PTA-SA.

 Cortisone acetate is formulated with PTA-SA.

 Formulation of drug bethanechol which is potent


acetyl choline esterase-resistant cholinomimetic for
Alzheimer’s disease.

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POLYPHOSPHAZENES
 Long chain backbone of alternative
nitrogen and phosphorus atom with two
groups attached to each other.

 Two types of polyphosphazenes.


1) Strong hydrophobic like
fluoroalkoxy side chain, aryloxy
phophazenes.
2) Hydrophilic polyphosphazenes
contain short chain of aryl amine side
groups, alkyl ether side chain.
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 Good candidate for implantable device
which is easy to fabricate and flexible.
 They are surface tailored to retard the
blood clotting.
 Amphiphillic polyphosphazenes have both
hydrophilic and hydrophobic groups.
 Certain derivative shows hydrogel
characteristics such as they swell up into
gel.

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APPLICATION
 Drug containing COOH groups (salicylic acid) could
be linked to this polymer by amide linkage to
prepare controlled release prodrug.

 Used as hydrogel:
 Intraocular lenses.
 Soft tissue prosthesis (artificial replacement
for a missing tissue).
 Substrate for enzyme and antigen.
 Polymer bound platinum antitumor agent are
available having better therapeutic effect & good
pharmacokinetics properties.

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POLY-E-CAPROLACTONE
 Shows heterogeneous degradation by
micro-organism in the environment.

 Good biodegradability and high


permeability & lack of toxicity.

 Synthesis by oxidation of cyclohexanone


with per acetic acid.

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APPLICATION
 Drug like tetracycline, 5-fluoro
Uracil, chlorpromazine, naloxanes
are given with this polymers.

 polymer Fiber used to control the


release of herbicide in an aquatic
environment.

 Reservoir devices for delivery of


steroid like levonorgestrol.
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PSEUDOPOLY(AMINO
ACID)
 Give good mechanically strong implants but
have gross toxicity and tissue incompatibility.

 Synthetic poly (amino acid) derived from


single amino acid is insoluble has high
melting point & can not be processed into
various shapes.

 Pseudo peptide denote peptide in which some


or all amino acid are linked by bonds other
than conventional peptide linkage.

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APPLICATION
 Polymer used for antigen delivery
that is for effective vaccination.

 Very useful in delivery of variety of


veterinary product.

 Suitable for delivery of important


peptides like enkephalins.

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NATURAL POLYMERS
 ADVANTAGES
 readily available natural
polymers.
 relatively inexpensive.
 chemical modification is possible
easily.

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COLLAGEN
 Unique structural properties therefore it
can fabricated into variety of forms
including films, inserts.

 Collagen is found in animal tissue usually


present in the tissue of skin and tendon.

 Has advantages of easy purification and


isolation in large
quantities,biocampatibility,non toxic to
most tissue.
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APPLICATION
 Pilocarpine films used for controlling
elevated intraocular pressure.

 Gentamycin films to treat bacterial eye


infection.

 Collagen shield made from porcine source


and given to patients with corneal
abrasion or after corneal surgery.

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ALBUMIN
 Major plasma constituent in body and
features like reported biodegradation,
lack of toxicity, non- antigenicity and
readily available.

 APPLICATION
1. Drugs like doxorubicin,mitomycine,5-
fluorouracil are given because tumor cells
ability to take up albumin.

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STARCH
 Most abundant biodegradable polymers
which belong to class of polysaccharide.
 It consist of glycopyranose units which
under hydrolysis yields D-glucose.

 APPLICATION
starch microspheres used for intranasal
administration of insulin.

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GELATIN
 It is protinaceous biodegradable polymers
obtained from partial hydrolysis of collagen
derived from skin, connective tissue and
bones of animal.
 Two types
a] Type A : acid treated .
b] Type B : alkali treated.
mostly fabricated into microspheres.

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APPLICATION
 Good carrier systems for number of
anticancer agents that is tumors which do
not take albumin redially take up gelatin.
 Used as an immunoadjuvant because
gelatin is susceptible to macrophage
recognition. The gelatin containing the
antigen can carry it directly to the
macrophages and antigen is released as
gelatin degrades which leads to enhance
production of antigen specific antibodies.

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Dextran
 It is a carbohydrate used to
prepare hydrogel, which is
biodegradable and
biocompatible. Usually available
as microspheres
 Application
Acts as a good carrier for a
variety of drugs, proteins.

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OTHER NATURALLY OCCURING
POLYMERS
 Hyaluronic acid
 Fibrinogen
 Deacetylated Chitin: aid weight loss
and cholesterol lowering agents.
 Carragenan
 Alginate

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SOME PRODUCT BASED ON
BIODEGRADABLE POLYMERS
1. Zoladex (Astra zeneca) :
Is supplied as sterile biodegradable product containing
goserlin acetate equivalent to 3.6 mg of goserlin given as
sub cutaneous injection with continuous release over 28
days. It dispersed in matrix of DL lactic & glycolic acid.
2. Lupron depot :
FDA cleared PLGA product
microsphere formulation based on degradable polymers
of polylactic acid & poly (lactic/glycolic acid).
3 Gliadel wafer.
contain cancer chemotherapeutic drug carmustine
fabricated from poly (caboxyphenoxy propane: sebacic
acid)

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REFERENCES

Biodegradable polymers as Drug delivery
systems Mark chasin, Robert Langer,volume 45.

Indian Journal of pharmaceutical sciences sep-oct 2007.69(5):609-
734. V. B. Kotwal, Maria Saiffee, Nazma
Inamdar and Kiran Bhise, Allana College of
Pharmacy, K. B. Hidayatullah Road, Azam
Campus, Pune - 411 001, India.

Encyclopedia of pharmaceutical Technology
volume 2 : James swarbrick, James.c.Boylan,P-
1

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REFERENCES

Catia Bastioli, Handbook of Biodegradable Polymers,Rapra
Technology Limited,UK,4-18.

Polymers for Controlled for controlled Drug Delivery

Peter J.Tarcha,Ph.D.Abbott Laboratories, North


Chicago,Illinois,CRS Press,Bostone P 127-147.

Polymeric Drugs & Drug delivery systems,
Raphael M.Ottenbrite ,Ph.D,Sung Wan
Kim,Ph.D.CRS press new york 57-112.

Handbook of biodegradable polymers editor
castia Bastioli rapra technology, UK 1-25.

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