Polymer Polymer sciencescience

By Viraj Sukthankar. F.Y m-pharm.

Pharmaceutics dept.

Contents..

INTRODUCTION. POLYMER CLASSIFICATION. GENERAL MECHANISM OF DRUG

RELEASE FROM POLYMER

APPLICATION OF POLYMERS IN FORMULATION OF CONTROLLED DRUG DELIVERY SYSTEM.

REFERENCES.

INTRODUCTION

Polymer SciencePolymer Science or Macromolecular Science is a subfield of materials Science concerned with polymers, Primarily synthetic polymers such as plastics and elastomers.

Polymer Science has been the backbone for the development of new formulations for past few years and its advances have led to development of several applications in pharmaceutical science.

Polymers Polymers are high molecular weight compounds or

macromolecules composed of many repeating subunits called “MONOMERS”, connected by Covalent bonds or chemical bonds. The reaction involving combination of two or more monomer units to form a long chain polymer is termed as polymerization.

These are widely used as Pharmaceutical aids like suspending agents, Emulsifying agents, Adhesives, Coating agents, Adjuvants etc. Packaging material and medical devices both in conventional and controlled drug delivery systems.

Other definitions-

A Polymer is like a thread that is joined by many coins punched through the center, in the end we get a string of coins, the coins would be the monomers and the chain with the coins would be the polymer.

E.g. Polyethylene = Ethylene-ethylene-ethylene-ethylene-…

Polymers are long chain giant organic molecules assembled from many smaller molecules called monomers. A polymer is analogous to a necklace made from many small beads.

Historical BackgroundThe work in polymer science was started in 1811 by Henri braconnot.The term polymer was coined in 1833 by Jon's Jacob Berzelius to describe the relationship of ethylene to butane and higher homologs.Bakelite was introduced in market in 1909 by reacting phenol and formaldehyde at precisely controlled temperature and pressure.Flory, Mark and other in 1940’s were responsible for rapid expansion of polymers, including detailed studies of materials of increasing commercial value.

Drugs Used Category Method Used Polymer Used

Zidovudine Anti-viral Direct Compression

HPMC-K4M, Carbopol-934, EC

Venlafexine Anti-depressant Wet Granulation Beeswax, Carnauba wax

Domperidone Anti-emetic Wet Granulation HPMC-K4M, Carbopol-934

Ibuprofen Anti-inflammatory Wet Granulation EC, CAP

Miconazole Anti-fungal Direct Compression/ Wet Granulation

Pectin, HPMC

Verapamil Ca+2 channel blocker

Direct Compression

HPMC-K100M, HPMC-K4M, HPMC-K15M

Diethyl carbamazepine citrate

Anti-filarial Wet Granulation Guar gum, HPMC-E15LV

Amlodipine Anti- arrythmatic Direct Compression

HPMC, EC

Chemical nature of some common polymers

1. Polyethylene (LDPE) (Addition polymer) Formula- -(CH2-CH2)n- Monomer- Ethylene (CH2=CH2) Properties- Soft, Waxy Solid Uses- Film Warp, Plastic bags etc.

2. Butyl Rubber (Copolymer) Monomer A- H2C=C(CH3)2 Monomer B- H2C=C-CH-CH2

Properties- Elastic Strong rubber material. Uses- Inner tubes of tires.

3.Polyvinyl Chloride (PVC) (Addition Polymer)Formula : -(CH2-CHCL)n-Monomer : Vinyl Chloride (CH2=CHCL)Properties : Strong rigid Solid Uses : Pipes, Siding, Flooring.

4.Polypropylene (Diff Grades) (Addition Polymer)Formula : -[CH2-CH(CH3)]n-Monomer : Propylene (CH2=CHCH3)Properties : Atactic, Soft, Elastic solidUses : Similar to LDPE carpet, upholstery etc.

Some important Polymers used for drug delivery

Hydroxyl propyl Methyl Cellulose

It is a semisynthetic, Inert, Viscoelastic polymer used as an ophthalmic lubricant as well as an excipient and controlled delivery component in oral medicaments. It is also found in variety of commercial products.

Description- It is solid and slightly off-white to beige powder in appearance and may be formed in granules.

Category- Suspending Agent, Viscosity enhancer, Tablet binder, Coating agent, Film forming agent, Emulsion stabilizer etc.

Method of Manufacture-

Cellulose fibers obtained from cotton linters or wood pulp are treated with caustic soda. Alkali cellulose thus obtained is in turn treated with methyl chloride and propylene oxide to produce methyl hydroxyl propyl esters of cellulose. Fibrous reaction product is than purified and ground to fine uniform powder or granules.

Micro crystalline cellulose (MCC)

MCC is a unique ingredient. In water with shear it forms three dimensional matrix comprised of invisible microcrystals that form an extremely stable, thixotropic gel. It functions at any temp and provides superior freeze and heat stability to finished products.

Category- Tablet and capsule diluent, Tablet disintegrate, Suspending agent, Viscosity enhancer etc.

Description- Purified, Partially depolymerized cellulose occurs as a white odorless crystalline powder composed of porous particles. Available in diff particle size grades and prop.

Method of manufacture –

MCC is manufactured by controlled hydrolysis of a-cellulose, Obtained as a pulp from fibrous plant materials, With dilute mineral oil and acids solutions. Following hydrolysis, the hydrocellulose is purified by filtration and aq. Slurry is sprayed dried to form dry, porous particles of broad size distribution.

Guar gum-

Guar gum is a natural polymer obtained from ground endosperm of guar beans.

Category- Tablet binder, suspending and viscosity increasing agent, Tablet disintegrating agent etc.

Chemistry- Chemically gaur gum consist of polysaccharides composed of sugars galactose and mannose.

Description- White to yellowish-white powder. Odorless and bland in taste.

Method of manufacture –

The gum consist of the pulverized endosperm of the seed of gaur. The seed hull can be removed by grinding, After soaking in Sulfuric acid or water or by charring. The separated endosperm is ground into diff particles size depending on final application.

Polyethylene Glycol (PEG)

Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine.

Category- Suppository base, Solvent, Tablet and capsule lubricant, Ointment base etc.

Diff grades of PEG-

PEG-200, 300,400,600,800,1000,1500,1540,2000,3000,4000,6000,8000, 20,000, 35,000.

Description- Clear, Colorless or Slightly Yellowish, Viscous liq.

Method of manufacture-

Condensation polymers of ethylene oxide and water are progressively formed under pressure in the presence of a catalyst.

CHARACTERISTICS OF IDEAL POLYMER SYSTEM

Inert and compatible with environment. Nontoxic. Easily administrable. Easy and inexpensive to fabricate the dosage form. Good mechanical strength.

1. CLASSIFICATION OF POLYMERS

POLYMERS NATURAL SYNTHETIC SEMI-SYTHETIC

Biodegradable Non biodegradable

Lactides, glycolides

and their copolymers,

polyanhydrides Acrolein, epoxy polymers

Proteins

Carbohydrates

Nucleic acids

a. Natural polymers: Natural polymers are derived from natural sources and can be polysaccharides and proteins in chemical nature.

E.g. Collagen, Albumin, Starch, Silk, Proteins, Wool, Natural rubber etc.

b. Synthetic polymers: Synthetic polymers are of artificial origin which consist of fibers like Teflon and Dacron, Synthetic Rubbers, Plastics and PVC.

Synthetic polymers are further classified into two main categories i.e.

1. Biodegradable polymers: E.g. Proteins, Collagen Polysaccharides etc.

2. Non-biodegradable polymers: E.g. Acrolein, Epoxy Polymers.

Bio- degradable polymers are further classified into

1. Natural bio-degradable polymers- These polymers are very common in nature. Natural biodegradable polymers like collagen, albumin, gelatin, hemoglobin etc. have been studied for medical & pharmaceutical applications.

The use of these polymers is limited because of their high costs and questionable purity.

Examples-Albumin, Collagen, Gelatin, Starch etc.

2. Synthetic Bio-degradable polymers -These type of polymers are preferred rather than natural bio-degradable polymers due to their inertness and easy and cheap formulation.

Synthetic bio-degradable polymers have following advantages over natural ones : Localized delivery of drug. Sustain delivery of drug. Stabilization of drug. Reduced side effects etc.

Examples- Poly lactide homopolymer, Polyester,

L-PLA etc.

c. Semi-Synthetic Polymers –

This type of polymers are derived from naturally occurring polymers by means of chemical modifications.

E.g. Vulcanized rubber, Gun cotton, Cellulose diacetate, HPMC etc.

Vulcanized rubber is used in making tires as the process of vulcanization increases the mechanical strength of natural rubber.Gun cotton which is a cellulose nitrate is used in making explosives.

Cellulose on acetylation with acetic anhydride in the presence of sulfuric acid forms cellulose diacetate which is used in production of treads and materials like films, glasses etc.

Vulcanization of rubber

2. Based on their interaction with water

Polymer

Non-Biodegradable Hydro gels Soluble Bio-Degradable

Polymer. Polymer. Polymer.

e.g. PVC, PVA . E.g. PVP. E.g. HPMC, PEG. E.g. PAA, PGA

3. Based upon linkage it can be classified as:

a. Linear polymer: Molecules has definite backbone and does not have long chain branches.

e.g. Polyformaldehyde,Polyesters,

Polycarbonates etc.

b. Branched polymers: It has long chain branches that cannot be defined. It may also have short chain branches.

E.g. Polyethylene, HPLD Polyethylene etc.

C. Cross-linking polymers: In this type all molecules are chemically bonded together, forming a three dimensional network. The bonding is usually covalent but other types such as ionic bond are also possible.

Cross-linked polymers are produced from linear and branched polymers or directly from chemical precursor.

E.g. Natural rubber, polyacrylamide gels,

epoxies, Alkyd resins etc.

4. Based on polymerization mechanisms:a. Addition polymers:

Addition polymers are formed when monomer units are separately added to form long chains without elimination of any by-product molecules.

This polymers are formed by reactions between monomer molecules possessing multiple bonds.

E.g. Polyethylene, Polypropylene, Styrene- butadiene rubber etc.

b. Condensation polymers.

Condensation polymers are formed when the monomers containing active functional groups react together with the elimination of a small molecule like water, ammonia, alcohol etc.

E.g. Nylon-66, Polyester, Bakelite etc.

5. Based on polymerization mechanisms:

1.Chain polymerized polymer:

Involves initiation, propagation, and

termination.

E.g. Polystyrene

2.Step growth polymerized polymer:

No discrete initiation, propagation takes place but instead involves sp. Reaction b/w functional group.

E.g. Nylon

Addition: one monomer at a timeAlso called chain growth.

Condensation: Also called step growth.

6. Based on composition:

A. Homopolymer:Polymers formed from one kind of monomer are called a homopolymer like -A-A-A-A- e.g. Polyethylene, polystyrene

B. Copolymer:Polymers formed from more than one kind of monomer unit is called a co-polymer or mixed polymer like -A-B-A-B-A-B- e.g. Silicone, Ethyl cellulose

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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.

GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER

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.

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 no changing 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) is transdermal system.

Bio degradation of polymers -Bio degradation is the chemical changes that alter the molecular weight or solubility of the polymers.Bio erosion may refer to as physical process that result in weight loss of a polymer device. The possibility for a polymer to degrade and to have its degradation by products assimilated or excreted by living system is designated as Bio Resorbable.The erosion of polymers basically takes place by two methods:-

1.Chemical erosion

2.Physical erosion

Chemical ErosionBio erosions through chemical mechanisms are explained below-Mechanism-I :It describes the degradation of water soluble macromolecules that are cross-linked to form three-dimentional network

Degradation in these systems can occur by

•Type (1A)- Degradation occur at crosslinks to form soluble backbone polymeric chains. It provides high molecular weight, Water soluble fragments.

•Type (1B)- Degradation occur to form water-soluble fragments. Such type provides low molecular weight, water soluble oligomers and monomers.

Mechanism-II : Describes the dissolution of water insoluble macromolecules with side groups that are converted to water insoluble polymers as a result of ionization, Protonation or hydrolysis of the groups.

Molecular weight remains unchanged. Materials showing this type of erosion include

Cellulose acetate derivatives,

Co-polymers of maleic anhydride.

Mechanism-III : Describes the degradation of insoluble polymers with liable bonds. It forms low molecular weight, water soluble molecules.

Polymers undergoing this type of erosion include

Poly(lactic acids)

Poly(glycolic acid) and their co-polymers etc.

Physical erosion The physical erosion mechanisms can be characterized as heterogeneous or homogeneous.Most polymers undergo homogenous erosion that means the hydrolysis occur at even rate through out the polymeric matrix.In homogenous erosion, there is loss of integrity of the matrix or polymer.

In heterogeneous erosion, also called as Surface Erosion. The polymer erodes only at the surface and maintains its physical integrity as it degrades.Highly crystalline polymers tend to undergo heterogeneous erosion.

APPLICATIONS OF POLYMERS IN

CONTROLLED DRUG DELIVERY

1.ORAL DELIVERY SYSTEM:

These techniques are capable of controlling the rate of drug from the delivery systems that can be utilized for controlled delivery of drugs.

Some of novel drug delivery system for oral controlled release drug administration include:

Osmotic pressure controlled GI delivery system.Diffusion controlled GI delivery system.Bio[muco]adhesive GI delivery system.

Osmotic Pressure Controlled GI delivery system:

Semi permeable membrane made from biocompatible polymers.

E.g. cellulose acetate E.g. of such type of system include

Acutrim tablet which contains Phenylpropanolamine as a drug.

Gel diffusion controlled GI delivery system: Fabricated from gel forming polymers such as

CMC.

Bio adhesive GI drug delivery system: It is capable of producing an adhesion interaction

with a biological membrane. E.g. Carbopol.

2.Transdermal drug delivery system:

Mostly used when the medicaments are applied on

topical route

E.g. Transdermal patch of scopolamine, nitro glycerin etc.

Advantages:They permits easy removal and termination of drug action in situation of toxicity.Problems encountered with oral administration like degradation, gastric irritation etc. are avoided.

3.Ocular Drug Delivery System.

It allows prolonged contact of drug with the surface of the eye.

Highly viscous suspension and emulsion are prepared to have such purpose but these preparations does not achieve this purpose at controlled rate.

E.g. Pilocarpine ocular insert used in treatment of glaucoma.

Other applications:

Drug delivery and the treatment of diabetes:

Here the polymer will act as a barrier between blood stream and insulin.

E.g. Polyacrylamide or N,N-Dimethyl amino ethylmetha acrylate.

Drug delivery of various contraceptives and hormones:

It consist of drug saturated liquid medium encapsulated in polymeric layer which controls the concentration and release of drugs into the blood stream.

E.g. Medoxy progesterone acetate, Progestasert, Duromine etc.

Polymer Membrane Permeation-Controlled Drug Delivery Systems

E.g. progestasert

Drug reservoir

Polymer layer

Various uses of Polymers in pharmaceutical sciences:

1. Formulation of Matrix tablets.

2. Formulation of Nanoparticles.

3. Formulation of solid dispersion.

4. In targeted drug delivery systems.

5. In the preparation of Polypeptide vesicles for drug delivery.

6. In formulation of cross linked Polymers.

7. Micelles for cancer therapeutics.

Imp. Questions from this topic -

Classify Polymers with examples?Discuss imp. Polymers used in design of controlled drug delivery system?Give an account on pharmaceutical applications of polymers? Discuss biodegradable polymers used in formulation of controlled release systems?

REFERENCES

Targeted and control drug delivery by S.P.Vyas and R.K.Khar. Pg. no 417 to 422.

The eastern pharmacist-august,1998, vol. no 41. Remington : The science and practice of pharmacy.

Vol.no 1 [20th edition] www.google.com Bio pharmaceutics and pharmacokinetics by

D.M.Brahmankar and Sunil.B.Jaiswal.

Thank you