Introduction:
“Polymer” is derived from Greek words “Poly'' meaning many and “Meros” meaning parts.
Polymers have very large molecular weights and are made up of repeating units (or monomers) throughout their chains.
Polymers are a subset of macromolecules.
A monomer is a small molecule that combines with other molecules of the same or different types to form a polymer.
If two, three, four, or five monomers are attached to each other, the product is known as a dimer, trimer, tetramer, or pentamer, respectively.
An oligomer contains from 30 to 100 monomeric units.
Products containing more than 200 monomers are called polymers.
Polymers can have different chemical structures, physical properties, mechanical behavior, and thermal characteristics.
classification of polymers.
Polymers can be classified in different ways, as following,
Based on the origin
Based on the Backbone
Based on the polymerization process
Based on the types of monomer
Based on the Line Structure
Based on thermal characteristics
Based on interaction with water
Based on stimulus response
Based on Morphology
Based on the presence of carbon (organic and inorganic)
Classification of Polymers Based on the Origin
Natural Polymers
Protein-based:
Albumin, collagen, gelatin, etc.
Polysaccharides:
Agarose, alginate, carrageenan, chitosan, cyclodextrins, dextran, hyaluronic acid, polysialic acid, etc.
Synthetic Polymers
Biodegradable Polyesters:
Poly(lactic acid) (PLA), poly (glycolic acid) (PGA), poly (hydroxybutyrate) (PHB), poly (Ɛ-caprolactone) (PCL), poly(β-malic acid) (PMA), poly(dioxanes) (PDA) etc.
Polyanhydrides:
Poly(sebacic acid) (PSBA), poly(adipic acid) (PAPA), poly(terephthalic acid) (PTA) and various copolymers etc. Polyamides include poly(imino carbonates) (PIC), polyamino acids (PAA), and others.
Phosphorus-based:
polyphosphates, polyphosphonates, polyphosphazenes, etc.
Others:
Poly(cyanoacrylates) (PCA), polyurethanes, polyortho esters, polydihydropyrans,polyacetals etc.
Non-biodegradable Cellulose derivatives:
carboxymethyl cellulose (CMC), ethylcellulose (EC), cellulose acetate (CA), cellulose acetate propionate (CAP), hydroxypropyl methylcellulose (HPMC), etc.
Silicones:
Polydimethylsiloxane (PDS), colloidal silica, etc.
Acrylic polymers:
Polymethacrylates (PMA), poly(methyl methacrylate) (PMMA), poly hydro(ethyl methacrylate) (PHEM) etc.
Others:
Polyvinyl pyrrolidone (PVP), Ethyl Vinyl Acetate (EVA), poloxamers, poloxamines, etc.
Semi-synthetic Polymer:
Hydrogenated natural rubber, cellulose nitrate, methyl cellulose, etc. are chemically modified polymers.
Based on the types of monomer:
Homopolymer:
A polymer containing a single type of repeat units is called a homopolymer.
e.g., polystyrene.
Copolymer:
If a polymer is made up of two different monomers then it is called copolymer.
e.g., styrene butadiene (SBS) rubber and Sty-co-An.
Ideal Characters of polymers
It should be inert and compatible with the environment.
It should be non- toxic and physiologically inert.
It should be easily administrable.
It should be easy to fabricate and must be inexpensive.
It should have good mechanical strength.
It must have compatibility with most of the drugs.
It must not adversely affect the rate of release of the drug.
It must not have tendency to retain in tissue and must be a good biodegradable material.
Properties Of Polymers
Crystallinity:
Partial alignment of molecular chains is associated with the process of crystallization of polymers.
Dyeing of polymers gets affected by crystallinity.
Amorphous form is much more prone to dyeing as compared to crystalline form because the dye molecules penetrate much easier through amorphous regions.
Viscosity:
Viscosity increases, the sustained drug release is prolonged.
Polymer complexes:
Polymers provide ample opportunity for the formation of complexes in solution.
Such macromolecular reactions are highly selective and strongly dependent on molecular size, conformation heat etc.
Biological macromolecules undergo complex reactions, which are often vital to their activity.
Syneresis:
The separation of liquid from a swollen gel is known as syneresis.
This is a form of instability in aqueous and non-aqueous gels.
Separation of a solvent phase is thought to occur because of the elastic contraction of the polymeric molecules.
In the swelling process during gel formation the macromolecules involved become stretched and the elastic forces increase as swelling proceeds.
Adsorption of macromolecules:
The ability of some macromolecules to adsorb at interfaces is being exploited in suspension and emulsion stabilization.
Gelatin, acacia and proteins adsorb at the interface.
Sometimes such adsorption is unwanted, addition of albumin to prevent adsorption is now common practice.
Bio Adhesiveness of water- soluble polymers:
Adhesion between a biological surface and a biological surface and a surface of a hydrophilic polymers, arises from interactions between the polymer chains and the macromolecules on the mucosal surface.
To achieve maximum adhesion there should be maximum interaction between the polymer chains of the bioadhesive and the mucus.
The charge on the molecules will be important and for two anionic polymers maximum interaction will occur when they are not charged.
Penetration and association pH must be balanced.
The adhesive performance of polymers can be excellent (e.g. carboxymethylcellulose), good (Carbopal), fair (gelatin) or poor (povidone).
Polymer dissolution:
Polymer dissolution in solvents is an important area of interest in polymer science and engineering because of its many applications in industry such as membrane science, plastics recycling and drug delivery.
Unlike non-polymeric materials, polymers do not dissolve instantaneously, and the dissolution is controlled by either the disentanglement of the polymer chains or by the diffusion of the chains through a boundary layer adjacent to the polymer-solvent interface.
Mechanism Of Drug Release By Polymers
DISSOLUTION:
The drug release by dissolving polymer is by penetration of dissolution fluid.
In a Sustained or controlled drug delivery system, a drug is dispersed (matrix system) or encapsulated (individual drug particles) with slowly dissolving polymers.
The rate of penetration of the dissolution fluid into the matrix determines the drug dissolution and subsequent release.
The penetration of dissolution fluid is, however, dictated by the matrix, porosity, presence of hydrophobic additives and the wettability of the system and surface of the particle.
In encapsulated system, the coat thickness and its aqueous solubility determine the time required for dissolution of coat one can formulate a repeat action or sustained release product by using a narrow or a wide spectrum of coated particles of varying thickness, respectively,
Diffusion:
Diffusion occurs when the drug passes from the polymer matrix into the external environment.
In a controlled drug delivery system, drug is homogeneously dispersed in a polymer matrix (monolithic matrix system) or drug (solid, dilute solution or highly concentrated solution) within a polymer matrix and surrounded by thin film (reservoir system).
Diffusion occurs when the drug passes from the polymer matrix into the external environment.
With the passage of time and continuous drug release, the delivery rate normally decreases in this type of system since the bioactive agent has to traverse a long distance progressively and thereby requires a longer diffusion time for ultimate delivery of drug(s).
In a swelling controlled drug delivery system, drug release by swelling of polymer followed by diffusion of drug with or without dissolution.
Dissolution and Diffusion:
Drug release by dissolution of polymer followed by diffusion of drug.
In controlled drug delivery systems consist of the drug core enclosed in partially soluble membrane.
Dissolution of part of outer membrane leads to facilitated diffusion of the contained drug through pores in the coating by dissolution and diffusion controlled release mechanism of polymer
Erosion:
The active agent is contained in a core surrounded by a bioerodible rate-controlling membrane.
Such a system combines the attributes of a rate-controlling polymer membrane, which provides a constant rate of drug release from a reservoir-type device, with erodibility, which results in bioerosion and makes surgical removal of the drug-depleted device unnecessary.
Because constancy of drug release demands that the bioerodible polymer membrane remain essentially unchanged during the delivery regime, significant bioerosion must not occur until after drug delivery has been completed.
Thus, polymer capsules will remain in the tissue for varying lengths of time after completion of therapy.
The active agent is covalently attached to the polymer backbone and is released as its attachment to the backbone cleaves by hydrolysis of bond A.
Because it is not desirable to release active agent molecules with polymer fragments still attached, reactivity of bond A should be significantly higher than reactivity of bond B.
4. Ion exchange:
Drug release by reversible exchange of ions (in drug-ion exchange resin complex).
Ion exchange resins are used to sustain the effects of drugs based on the concept that negatively or positively charged drug moieties combine with appropriate resins producing insoluble poly salt resonates.
Where R-SO3-H + and R-NH3+OH- represent cationic and anionic resins, whereas H2N-A and HOOC-B depict basic and acidic drugs respectively.
Where administered orally resins come in contact HCl with pH 1.2 following reaction takes place.
R-SO3-H+ + H2N-A → R-SO3- + H3N+ -A
R-N+H3- + HOOC-B → R-N+H3-OOC-B + H2O
Applications of Polymers in Drug Delivery System:
Tablets:
Tablets are the most commonly used dosage form for pharmaceutical preparations meant to be taken orally.
Release of drugs from the tablet can be controlled by altering the design and content of the formulation.
In tablets the polymers are used as a Disintegrants and Binder.
E.g. Starch, cellulose, Alginates, polyvinylpyrrolidone, sodium CMC etc are used as disintegrants.
Polymers used as binders are
e.g. Starch, HPMC, Gelatin, Alginic acid, polyvinylpyrrolidone, Sucrose, Ethyl cellulose.
Polymers are also used to mask the unpleasant taste of the drug and also for enteric coating of tablets
e.g. Shellac and zein.
Capsules:
Capsules are generally composed of gelatin.
The composition of gelatin varies so gelatin is of two types that is hard gelatin and soft gelatin.
Fillers such as MCC and starches are used to fill up the volume in the capsule.
To overcome the problem of aggregation various polymers such as starch and sodium starch glycolate are mixed with capsule containers.
In Parenterals:
In Parenteral the various polymers like Methacrylic acid act as an Interferon inductor which induces the interferon in cancer like disease.
Methacrylic acid alkyl amide acts as a plasma expander which increases the plasma level in the body.
Some Vaccines are transpired by using polymer because which disintegrate in GIT tract, example Methyl methacrylate
Polymers in Disperse systems:
Various synthetic and natural hydrophilic polymers are extensively used to enhance the physical stability of pharmaceutical disperse systems. Examples of these include alginates, acacia, carrageenan and xanthan gum, whereas a wide range of synthetic polymers has also been used for this purpose, e.g., cellulose ethers, poly(acrylic acid), PVP and PVA.
Polymers in Gels:
Gel systems consist of physical or chemical cross-links between adjusted polymer chains that restrict chain mobility.
Gel has rheological properties.
Cross-linked gels are most commonly known as hydrogels.
They are also known a s smart polymers because they show different gelling properties in different environments of water.
Most commonly used hydrogels are poly (hydroxyethyl methacrylate), poly (methacrylic acid) and poly (acrylamide).
In pharmaceutical industries cross-linked gels are primarily use for local drug delivery of drugs to skin, oral cavity, vagina and rectum.
Swelling Controlled Release Systems:
In many drug delivery systems, the dimensions of the dosage form will change during the course of drug release due to swelling of the polymer matrix.
Although the mechanism for drug release is diffusion, Examples of systems that exhibit swelling controlled release are physically crosslinked and chemically crosslinked gels.
In terms of controlled drug release, chemically Crosslinked hydrogels e.g., poly(hydroxyethyl methacrylate), have been used to provide controlled drug release from medical devices, whereas swelling controlled physical hydrogels may be easily manufactured by directly compression of drug with a hydrophilic polymer, e.g., HPMC.
Temperature Responsive Drug Release:
Some controlled systems for the administration of drugs are developed that use the temperature as an external stimulus.
The polymers used to obtain such release properties are referred to as thermoresponsive polymeric systems.
Typically, the homo and copolymers of N-substituted acrylic and methacrylate amides [e.g. poly (isopropyl acrylamide)], are used for this purpose.
More specifically, there are two types of thermoresponsive polymer systems namely those that exhibit positive and negative temperature dependency.
Polymers in the former category display an upper critical solution temperature below which polymer contraction occurs upon cooling.
Conversely, negative temperature dependent polymers have a lower critical solution temperature and will contract upon heating above the lower critical solution temperature.
pH Responsive Drug Release:
Within the gastrointestinal tract a range of pH values exist, ranging from about one in the stomach to neutrality within the intestine.
Targeting drug release within certain regions of the gastrointestinal tract as a method to enhance drug stability within acidic fluids or to reduce the irritant effects of certain drugs.
For example, enteric polymers have been used as tablet coatings for this purpose, examples of which include cellulose acetate phthalate and cellulose acetate butyrate.
These polymers are insoluble in low pH environments; however they are soluble in the less acid regions of the gastrointestinal tract.
Following dissolution of the enteric coating, the tablet and hence the drug will dissolve, thereby facilitating drug absorption.
Due to this pH dependent solubility, enteric polymers may be described as pH responsive polymers.
Transdermal drug delivery system:
Transdermal systems dependent on rate-controlling membranes are available for the delivery of nitroglycerin, scopolamine, oestradiol (estradiol), fentanyl and other drugs.
The barrier properties of skin are so variable, however, that one advantage of a rate-controlling system generally consists of a reservoir, a rate-controlling membrane and an adhesive layer.
Diffusion of the active principle through the controlling membrane governs release rate.
The active principle is usually present in suspended form; liquids and gels are used as dispersion media.
In a matrix system the active principle is dispersed in a matrix.
In Transiderm Nitro, the rate- controlling membrane is composed of a poly-ethylene/ vinyl acetate copolymer having a thin adhesive layer (membrane type).
Ocular drug delivery system:
Improving the ocular contact time of solutions utilizes the incorporation of polymers into an aqueous medium such as polyvinyl alchol (PVA), polyvinylpyrrolidone (PVP), methylcellulose, carboxymethylcellulose (CMC) and hydroxypropyl cellulose (HPC).
The increased solution viscosity reduces the solution drainage.
Ocusert has the drug reservoir as a thin disc of pilocarpine-alginate complex sandwiched between two transparent discs of microporous membrane fabricated from ethylene-vinyl acetate copolymer.
Commonly asked questions.
Define “Polymers. Give their classification, ideal characteristics and applications in pharmaceutical formulations.