ROLE OF POLYMERS IN

DRUG DELIVERY

Presented by;
Gul Rehman Elmi
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 CONTENTS
Matrix
systems
Conclusio
n Heparin
releasing
polymers

Recent Ionic
advances polymers

Miscelleneous Oligomers

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 MATRIX SYSTEMS

• Important for controlled-release (CR) devices

1. Dispersed matrix systems
• Non porous drug leaching
• Ease (manufacture by mixing drug and polymer only)
2. Porous matrix systems
• Drug is displaced by solvent
3. Reservoir-dispersed matrix systems
• Barrier layer is present at the surface of the device
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 MATRIX SYSTEMS

POLYMERS IN MATRIX SYSTEM

Polydimethyl siloxane
• Advantages
1. Elastomer with good mechanical properties
2. Highly permeable to hydrophobic drugs
3. Permeability not affected by biological fluids
4. Molded into a wide variety of shapes
5. Polymerized with simple techniques
6. Nontoxic 4
 MATRIX SYSTEMS

POLYMERS IN MATRIX SYSTEM

Polydimethyl siloxane
• Disadvantages

1. Impermeable to hydrophilic drugs

2. Allergic reaction on subdermal implantation

3. Permeability not easily varied by alterations in

polymer composition 5
 MATRIX SYSTEMS

POLYMERS IN MATRIX SYSTEM

Hydroxyalkyl Methacrylates
• Advantages

1. Non toxic

2. Minimal allergic response

3. Highly permeable to both hydrophobic and hydrophilic drugs

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 MATRIX SYSTEMS

POLYMERS IN MATRIX SYSTEM

• Copolymers of the hydroxyalkyl, methacrylates and

methyl methacrylate have increased mechanical strength
and compatibility to blood and Tissue
• Others polymers are ethylene vinyl acetate,
polyacrylamide, polyvinyl acetate, polyethylene, and
polyether urethanes
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 MATRIX SYSTEMS
FACTORS FOR DRUG RELEASE

S No. Drug load Dependency of drug

release
1. Homogenous ≤ saturation point • Initial drug load
matrix • Diffusion coefficient
2.Heterogeneou > Saturation point • Initial drug load
s matrix but < 10% w/w • Diffusion coefficient
• Saturation solubility
of drug
3. Porous > Saturation point • Channels fromed
matrix but > 10% w/w

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 HEPARIN - RELEASING
POLYMERS

• Work in heparin CR materials was accidentally initiated by

Gott et al., 1963
 Investigation on thromboresistance

 Colloidal graphite gave best results for thromboresistance

 Graphite-benzalkonium-heparin (GBH) surfaces heparin even

after 3 months of implantation in the venous system

• Disadvantage of GBH

Graphite can only be coated to rigid materials

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 HEPARIN - RELEASING
POLYMERS

Three surface treatments to overcome problems with GBH

1. Chloromethylation of styrene followed by quaternization with

dimethyl Aniline

2. Radiation grafting of vinyl pyridine to numerous polymers

followed by quaternization with methyl iodide or benzyl chloride

3. Incorporation of quaternizable monomers, such as vinyl pyridine,

into copolymer formulations.

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 HEPARIN - RELEASING
POLYMERS

• Heparinized cellulose membranes for kidney dialysis applications,

Merrill et al.

1. Convert secondary cellulose hydroxyl groups into primary hydroxyl

groups by ethylene oxide

2. React with ethyleneimine to produce aminated surfaces

3. Ionically bind heparin to the greatest extent.

• Result in Prolonged clotting time

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 IONIC POLYMERS

• Can be soluble and insoluble Polymer

• Ion exchange resins are investigated most extensively

• Chemical and physical properties of ion-exchange resins

depends on particle size and cross-linkage.
• ↓ particle size → less time required for reaction

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 IONIC POLYMERS

PRINCIPLE OF ION
EXCHANGE RESINS
• Positively or negatively charged drugs combined with resins yield
insoluble poly-salt resinates
• Administer it orally

• They will spend 2 h in the stomach (pH 1–2)

• Pass to the intestine and retain for 6 h or more, with a fluid of slightly
basic pH
• The drug then slowly liberated by exchange of sodium or chloride ions
present in the GI fluid. 13
 IONIC POLYMERS

• Criteria for drugs to be resinated

1. Having acidic or basic groups in their chemical structure
can be considered.

2. Biological half-life of drugs is to be 2–6 h.

3. Absorbed from all regions of the GI tract

4. Stable in the gastric juice

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 IONIC POLYMERS

• Ion-exchange carries ionic groups

1. Cationic exchangers
−SO3, −COO, and −PO3 2
2. Anionic exchangers
−NH3H, −NH2H, and −N−H.
• They determines its physical properties and loading capacity

• Carboxylic acid-type exchangers are prepared by

polymerization of organic acids (acrylic or methacrylic acid
in presence of cross-linking agent (e.g., a diacrylate or
divinyl benzene [DVB] 15
 IONIC POLYMERS

• Ion-exchange resins should be Insoluble and Swell able

• The extent of swelling depends on the degree of cross-

linking.
• By varying the DVB content, cross-linking and swelling can
be adjusted
• Commercial products usually contain 40%–55% DVB-
isomers and 45%–60% ethylstyrene
• Swelling also depends on Pore volume, pore diameter, and
the internal surface 16
 IONIC POLYMERS

TOXICITY OF RESINS

• Drug–resin combinations contain ≥ 60% resin

• Large quantities can disturb ion strength in body fluids and

cause harmful side effects

E.g., sulfonic and carboxylic acid anionic exchangers →

Hypokalemia and hypocalcemia in children

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 IONIC POLYMERS

RELEASE OF DRUG
• The release of drug from a polymeric salt occur in 4 stages

1. Penetration of the dissolving medium in dosage form

2. Swelling of the polymer with formation of a gel barrier

3. Release of the drug

4. Liberation of drug by an ion-exchange between polymeric salt

and the medium
• Slow dissolution of drug–polymer results in a prolonged release
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 IONIC POLYMERS

APPLICATIONS

• Adsorbents of toxins, as antacids, and as bile-acid binding

Agents
• Treatment of liver diseases, renal insufficiency, urolithic
disease, and occupational skin diseases
• Resinate prolonged release formulations

• DOA of a resinate formulations vary from patient to patient

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 IONIC POLYMERS

APPLICATIONS

1. Streptomycin alginates prepared by El-Shibini et al. was

effective in prolonged-release

2. Poly(galacturonic acid) used to prepare poorly soluble

quinidine salts, which is four times less toxic orally than the
sulfate salts because of slow release of quinidine

3. Long-acting chloramphenicol dosage forms prepared from

CMC by addition of aluminum sulfate (gel-forming agent)
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 IONIC POLYMERS

APPLICATIONS

• Drug–resin combination approach are applied to

sympathomimetics, antitussives, antihistamines, anticholinergics,
anthelmintics, antibacterials, morphine and salycylic acid
• Polymers are incorporated to

1. Reduce drug toxicity

2. Influencing the release profile

3. Providing protection
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 OLIGOMERS

• Low molecular weight polymers

• In the case of oral and intradermal administration, they transfer

the drug across physiological barriers
• Oligomeric or polymeric derivatives of drugs prepared by
forming

1. Polymerizable derivative of drug

2. Oligomeric matrices carrying chemical functions

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 MISCELLANEOUS

• The following polymers or polymeric materials for use in SR

formulations
1. Ethylcellulose and methyl stearate mixtures
2. Hydrated hydroxyalkyl cellulose
3. Salts of polymeric carboxylates
4. Chelated hydrogels
5. Cellulose ether compositions
6. Water-soluble coating resins
7. Polylactides
8. Silicone polymer matrix having microsealed compartments
9. Gelatin nanoparticles
10. Serum albumin spherules 23
Table 3.4

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 RECENT ADVANCES

• Natural polysaccharides for site-specific drug delivery to

colon.
• Polysaccharides have a wide range of molecular weights,
varying chemical compositions, low toxicity,
biodegradability, and high stability
• Natural and synthetic polymers are also used

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 RECENT ADVANCES

• Aqueous polymeric SR dispersion of small coated particles

of propranolol
• Polylactide-co-glycolide and polylactide polymer particles
entrapping immunoreactive tetanus toxoid (TT) were
prepared in order to study single-shot controlled release
vaccine formulation.

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 RECENT ADVANCES

• A delivery system using “Medisorb” bioresorbable polymers

• 50 microns microcapsules

• Injected via syringe.

• Dissolution of polymer depends on lactide, glycolide, or a

copolymer of the two.
• Copolymer blends can be formulated in varying ratios to yield
drug-release times ranging from 7 days to 1 year

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 RECENT ADVANCES

• A biodegradable polymer

Implanted at tumor sites in the brain by surgery

Slowly releases drug

Finally the polymer also dissolves.

• Alza Laboratories manufactures a “bioerodible” polymer
called Alzamer that is used to treat chronic diseases and to
provide contraception
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 RECENT ADVANCES

• Polymers have been used extensively in nanoparticles,

microcapsules, liposomes
• Drug is incorporated into the system without the formation
of a covalent bond between the drug and polymer

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 RECENT ADVANCES

• The polymers are checked for

Immunogenicity
Hemolytic activity
Pyrogenicity
Osmotic properties
Interaction with plasma components must be studied
before using

• For example, chondroitin sulfate (endogenous) might show

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toxicity
 RECENT ADVANCES

• Disadvantages of organic solvents in coating processes

1. Cost

2. Stringent environmental regulation

3. Safety hazards
• New aqueous polymeric dispersions have also been developed,

• New research era to maximize the use of water-dispersible

colloidal particles
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 RECENT ADVANCES

• Synthetic hydrogels are used in drug delivery systems

because

Permeability controlled for aqueous solutes

Exhibit favorable swelling Pressures

Have good biocompatibility.

• Hydrogels with multiblock copolymers containing hydrophilic
and hydrophobic blocks are used nowadays
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 RECENT ADVANCES

Polymers for transdermal drug delivery systems

1. In reservoir-type transdermal devices, polymers is used

with reservoir and in rate-limiting membranes

2. In matrix transdermal systems, polymers is used to form

the device and mediate drug absorption across the skin.

3. In adhesive-type systems, polymers is used as adhesives

and have been mixed with the drug

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 RECENT ADVANCES

• Reduce bitterness of erythromycin and clarithromycin,

by absorption to Carbopol.
• Mechanism
Dissolve predetermined ratios of drug and polymer in
water
The macrolide-Carbopol complexes were formed
• They give blood levels comparable to those from
conventional solid formulations
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 RECENT ADVANCES

Smart polymers for responsive drug delivery

1. Open loop system
• Externally regulated systems

• Apply external triggers for pulsatile delivery

• E.g., dendrimer-based contrast agent

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 RECENT ADVANCES

1. Closed loop system

• Self-regulated systems

• Approaches for the rate-controlling are thermal, and pH-

sensitivity.
• E.g., poly(2-(methacryloxy) ethyl phosphoryl choline-co-
poly (2-(di isopropyl amino) ethyl methacrylate

PMPC-PDPA diblock copolymers

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 RECENT ADVANCES

• Thiolated chitosan have Multifunctional polymers that

exhibit following properties
1. Mucoadhesive
2. Cohesive
3. Permeation-enhancing
4. Efflux pump inhibitory properties
• Useful in oral delivery, in matrix tablets and
micro/nanoparticulate systems.
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 RECENT ADVANCES

• List of polymer–protein conjugates in the market

Adagen, Zinoststin, Stimalmer, Oncaspar, Neulasta,
PEGAsys, PEG-Intron, ADI-PEG 20, Pagvisomant, PEG-
PGA and DON, Puricase of Peglotinase, Cimzia, CD 870,
and Certolizumab pegol.
• Polymeric micellar delivery systems of Cisplatin,
doxorubicin, and paclitaxel were in clinical trials (2007)

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 CONCLUSION

In drug delivery system design, following topics

have undergone extensive investigation:
soluble synthetic polymers, oligomers, copolymers,
biodegradable polymers, polymer-coated liposomes,
encapsulated drugs for cancer, colloid carrier systems, albumin
and gelatin microspheres, magnetic microspheres and
magnetically modulated systems, matrix devices, swellable
polymers and polymer-bioactive agent (or prodrug), hydrogels,
insulin delivery, and polymeric implants and performance
polymers.
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 CONCLUSION

• Currently, continuing significant advances in drug delivery

devices

1. Osmotic pumps

2. Implants

3. Dermal and oral drug delivery systems

4. Development of new drug delivery systems

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THANK YOU

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