INTRODUCTION:

Polymers are substances whose molecules have high molar masses and pressed together by a large number of repeating units. Polymers can change the flow property of liquid dosage form and also can form particles of solid dosage form. Polymers are the pillar of pharmaceutical drug delivery systems[1]. They are mainly used as stabilizer, taste-making agent, and proactive agent. Polymers are found in both naturally and synthetic origin. Between naturally occurring polymers are proteins, starches, latex and cellulose. Synthetic polymers are manufactured on a large scale and have a many properties and used[2].

The polymers are classified for the drug delivery system on the following characteristics:

· Origin- The polymers can be natural or synthetic, or a combination of both.

· Solubility- The polymer can hydrophilic or hydrophobic in nature.

· Chemical nature- It can protein based, polyester, cellulose derivatives, etc.

· Backbone Stability- The polymers can be degradable or non biodegradable [3, 4].

Polymers have been used as a main aid to control the drug release rate from the formulations. The pharmaceutical applications of polymers range from their use as binders in tablets and viscosity, flow controlling agents in liquids, suspensions and emulsions. Polymers can be used as film coatings for dissembles/mask the unpleasant taste of a drug, for enhance drug stability, for modified drug release characteristics, for controlled release (e.g. extended, pulsatile and targeted) and improved bioavailability[5].

Polymers act as inert carriers to which a particular drug can be combined. There are various advantages of polymer acting as an inert carrier, for example, the polymer improve the pharmacodynamic and pharmacokinetic properties of biopharmaceuticals by several sources such as, increases the plasma ½ life, decreases the immunogenicity, improve stability of biopharmaceuticals, increases solubility of low molecular weight drugs, and has capacity for targeted drug delivery[6].

Polymers are capable to:

· Extend drug availability if medicines are prepared as hydrogelsor microparticles.

· Favorably change the bio distribution, if prepared into dense nanoparticles.

· Allow lipophilic drug administration if prepared as micelles.

· Transport a drug to its usually inaccessible site of action if Prepared as gene medicines.

· Make medicines available in response to stimuli [7].

Classification Polymer^[5]:

Based on interaction with water:

· Non‐biodegradable hydrophobic Polymers:‐ Eg. Polyvinylchloride (PVC).

· Soluble Polymers:‐ E.g. HPMC, PEG.

· Hydro gels:‐Hydrogel is a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel, which has a water dispensing medium. Eg. Polyvinyl pyrrolidine

Based on polymerisation method:

·         Addition Polymers:An additional polymer is a polymer that creates several non-monomers units other than co-generation of products other than the usual.E.g. Alkane Polymers

·         Condensation polymers:Condensation Polymers are any type of polymer made by condensation reactions - where molecules come together - small atoms such as water or methanol E.g. Polysterene and Polyamide

Based on polymerization mechanism:

·         Chain Polymerization: Chain-growth polymorization is a polymerization system in which monomer molecules are added simultaneously on the active site of the growing polymer chain. Common types of plastic made by chain polymerization, e.g. Polyethylene, polypropylene and polyvinyl chloride (PVC)

·         Step growth Polymerization: Step-growth polymorization is a polymerization system in which bi-functional or multi-functional monomers are first-size, then the trimeters, long oligomers, and finally long chain polymers. Many naturally occurring and some synthetic polymers are produced by step-growth polymerization, e.g. Polyester, polyimides, polyurethanes etc.

Based on chemical structure:

· Activated C‐C Polymer:

· Inorganic polymers: Inorganic polymers are polymers with the structure of the skeleton, which does not include carbon atoms in Redbone. Inorganic polymers usually refer to a one-dimensional polymer, rather than cross-linked materials like silicate minerals. Eg. Polydimethylsiloxane

· Natural polymers:Natural polymers are created by life's life, which represent cell's macromolecular components. E.g. Proteins‐collagen, keratin, albumin, cellulose

Based on occurrence:

· Natural polymers: Natural polymers are made by living organisms, representing the macromolecular components of the cell.E.g. Proteins‐collagen, keratin, albumin, cellulose

·         Synthetic polymers:Synthetic Polymers are human-made polymers. From utility perspective, they can be classified into four main categories: thermoplastic, thermoset, alistomer and synthetic fiber. Eg. Polyesters, polyamides

Based on bio‐stability:

·         Bio‐degradable:Biodegradable polymers are special types of polymers that fall in the form of natural sub-products such as gas (CO2, N2), water, biomass and inorganic salts for the purpose of their purpose. These polymers are naturally and synthetic, and a large amount of esters, amide and ether functional groups. Eg. Polyglycolic acid(PGA), Polyhydroxy butyrate (PHB), Polyhydroxy butyrates-co-beta hydroxyl valerate(PHBV), Polycaprolactone(PCL), Nylon-2-nylon-6 etc.

·         Non Bio‐degradable: A non-biodegradable polymer is a polymer that cannot be biologically distracted by natural processes (via bacteria).Eg.Polythene, teflon, bakelite, polymethylmethacrylate, neoprene etc.

Characteristics of an ideal polymer:

· It should be versatile and requires a wide range of mechanical, physical, chemical properties

· It must be non-toxic and have good mechanical strength and should be administered smoothly.

·         It should be cheap and easy to make.

·         It is inactive to be compatible with tissues and environments[5].

Criteria followed in polymer selection:

·         Polymer soluble and synthesis should be easy.

·         It should have a quantitative atomic weight.

·         They should be compatible with the biological environment.

·         It should be biodegradable.

·         It is necessary to give a good drug polymer linkage[5].

Commonly Used Polymers in Different Dosage Form^[5]

Rosin:

Rozin's film biopiler and its derivatives have been mediated as film coating and micronecapitalizing materials for the continuous release of medicines. They are used in cosmetics, chewing plums, and dental varnishes.

Rosin is used to make round microcontrolles so that solvent is based on phase separation through evaporation. Rosin's combination with polyvinyl pyrolidon and debutil phthalate (30% w / w) produces great films with improved growth and tension power.

Chitin and Chitosan:

Chitin is a naturally abundant mucopolyacoxide and contains 2-acetamido-2-deoxy-B-D-glucose. Chitinus can be destroyed by Chitin. Chitosan is a random polysaccharide that is randomly distributed β- (1-4) -Link D-glucosamine (desiciated unit) and N-acetyl de glucosamine (acetylated unit). The most important asset of medicine is its positive charge under acidic conditions. This positive charge comes from the proponation of its free amino group. Positive charges mean that Chitta is insoluble in neutral and basic environments.

Zein:

Zinc is caused by alkohol-soluble proteins, which are contained in the endosperm tissue of biomegranate, as a by-product. Corn Processing Jenna has been used as food for food and medicines for many decades. Zinc is a cheap and most effective alternative that is used for the fast-moving synthetic and semi-synthetic film coatings currently being used for the microscope that allows extrusion coating.

Collagen:

Collagen is the most commonly found protein in mammals and is a major provider of tissue strength. It has been used in bioprosthetic implants and multiple organ tissue engineering, if it is not used for various types of surgery, cosmetics and medicines.

Starches:

This is the main type of carbohydrate reserve of green vegetation and is particularly present in seeds and underground organs. Starch comes in the form of granules (starch grains), the size and size characteristics of these species, such as the number of main components, amylos and amyloptin. Many starchs are identified for the use of the drug. These include maize (zi ma), rice (orijasativ), wheat (triticumostaveem), and potato (olmanumtuberosam). In order to deliver proteins or peptidic medicines, microkapes containing proteins and proteins inhibitors have been prepared. Starch / bovine serum alginine composite-walled micropsys were prepared using interfacial cross-linking with teraphthalolor chloride. During the cross-linking process, microcrux root or aminoproteinated proprietary was loaded by adding protein inhibitors in aquatic location. The protective effect of micro-organisms with aprotinin for bovine serum aluminum was exposed in vitro.

Polycaprolactone:

Polypiolactone (PCL) is biodegradable polyester in which the temperature is 60 degrees Celsius and 60 degrees Celsius is the transit temperature. Using a catalyst like stainless octanoet, PCL ε-caprolactone is made by ring opening polymerization. The most common use of polypecocoatronics is in the formation of special polyurethane. Polypechlactone provides good water, oil, solvent and chlorine resistance for polyurethane produced.

Polyorthoesters:

These materials have gone through many generations of synthetic rectification for the production materials which can be policed at room temperature which is not produced by the condensed by-products. These materials are hydraulic and hydraulic, which are acidic, but are stable in the base. They descend from the surface errors and degradation rates can be controlled by including acid and basic emitters.

Role of polymers in drug delivery:

1. Immediate release dosage forms:

Tablets:

Polymers including polyvinyl‐pyrrolidone and hydroxypropyl methylcellulose (HPMC) find uses as binders that help in the formation of granules that increase the flow and compaction properties of tablet formulations prior to tableting.

Capsules:

Number of the polymeric excipients used for “bulk out” capsule fills are the same as those used in immediate release tablets. Gelatine is used almost exclusively as a shell material for hard (two‐part) and soft (one‐part) capsules. Now a days HPMC has been developed and accepted as an alternative material for the manufacture of hard (two‐part) capsules.

2. Modified release dosage form:

Polymer has been evaluated to achieve gastro retention mucoadhesive and low‐density, with little success so far, for their efficiency to prolong gastric residence time by bonding to the mucus lining of the stomach and floating on top of the gastric contents respectively.

3. Extended release dosage forms:

Extended and sustained release dosage forms extend the time that systemic drug levels are in the therapeutic range and thus lower the number of doses the patient must take to continue a therapeutic effect thereby increasing compliance. The usually used water‐insoluble polymers for extended‐release applications are the ammonium ethacrylate copolymers (Eudragit RS and RL), cellulose derivatives ethylcellulose, and cellulose acetate, and polyvinyl derivative, polyvinyl acetate[8].

4. Gastroretentive Dosage Forms:

Gastroretentive dosage forms give another strategy for achieving prolonged release profile, in whichthe formulation will remain in the stomach for extended periods, releasing the drug in situ, which will then dissolve in the liquid and slowly pass into the small intestine[9].

Applications of Polymers:

1) Polymers in Tableting:

Tablet is kind of solid dosage form which is formulated by compressing therapeutically active ingredient with pharmaceutical excipients. Manufacturing polymers mostly used binders and disintegrants. Example of tablet binder are Methyl cellulose (Methocel), starch, gelatin, PVP, EC and HPMC. Examples of coating agent are Hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC). Disintegrants initiates disintegration of tablet by increasing surface area of particles. Examples of super disintegrants are Carboxymethyl cellulose (Ac-Di-Sol), starch, PVP and sodium CMC. MCC increases compressibility of tablet[10,11,12].

2) Polymers in Capsule:

Capsule are generally contained of gelatin. The composition of gelatin are of different types that are two types in that first one is hard gelatin and second one is soft gelatin. To fill up the volume in capsule Fillers such as MCC and starches are used. To reduce problem of aggregation different polymers such as starch and sodium starch glycolate are mixed with capsule container[10,11,12].

3) Polymers in disperse system:

It is heterogeneous thermodynamically unstable liquid system in which drugs material sometimes solid or sometimes liquid is dispers in dispersion medium. Suspensions, emulsions, creams, ointments and aerosols are used as pharmaceutical dispersion system. Examples of naturally occurring dispersing agents are Alginates, carrageenan and xanthan gum. And examples of semisynthetic agents are poly (acrylic acid), PVP, PVA and cellulose ethers[10,13,14].

4) Polymers in gels:

Gel system made up of physical or chemical cross-linked between adjust polymer chain moderate chain mobility. Gel has rheological properties. Cross-linked gels are generally called as hydrogels. They are also called as smart polymers because they gives different gelling properties in different conditions of water. Examples of hydrogels are poly (hydroxyethyl methacrylate), poly (methacry1ic acid) and poly (acrylamide). In pharmaceutical industries cross-linked gels are firstly use to local drug delivery of drugs for skin, oral cavity, vagina and rectum[11].

5) Polymers in transdermal drug delivery systems (patches):

For delivery of therapeutic agent across skin to systemic circulation transdermal drug delivery system are generally used. System has some applications in pain cure, termination of smoking, heart diseas es and hormonal substitution. In transdermal drug delivery system role of polymer is protective coverings and adhesives. Examples of Adhesives used are acrylates silicones and polyisobutylates[11,15,16].

6) Polymers in ocuserts:

In treatment of eye disorders like glaucoma ocusert is used. An example of Oxshort is therapeutic agent (Pilochropyin) of 20 grams H-1 or 40 g H-1 for a period of 7 days from implantation. Ocusert is elliptical shape implant having various layers. Poly (ethylene-co-vinyl acetate) is used for preparation of pilocarpinocusert[11].

7) Polymers in progestasart system:

In controlled drug delivery system medicated implant use for contraceptive purpose example of this is a Progestasart intra-uterine device. The drug release occurs by diffusion from progestasart this polymer act as a rate controlling membrane for drug release. Examples of polymer are used in such system are Polyethylene and poly(ethylene-co-vinyl acetate)[11]

8) Polymers in colon targeted drug delivery:

Polymers play a very important role in the colon-targeted drug delivery system. It protects from the disorders of the medicine and leaves the stomach and small intestines. It also ensures sudden or controlled release of medicines in the proximal colon[17].

9) Polymers in the mucoadhesive drug delivery system:

The new generation of mucosidive polymers for drug delivery will increase the time of polymers, increase penetration, site specific adhesion and enzymatic blocks, site specific macrocystic polymers, and can be useful for the treatment of various types of treatment. The polymers class is huge for the distribution of the therapeutic therapeutic macromolecules[18].

10)Polymers in sustained release:

Using polymer builds bio-stimulant microspeers and creates it with a new powerful osteogenic compound[19].

11) Polymers in floating drug delivery system:

Polymers are generally employed in the floating drug delivery system, so that gastrointestinal tract, which aims to distribute drugs in a particular area in the stomach. The natural polymers discovered for their potential potential for specific drug delivery include chitosan, pectin, zanthon gum, guar gum, gallon gum, gram gum, stem, starch, hask, starch, alghenetc[20].

12) Polymers in tissue engineering:

A wide range of natural origin polymers with specific targets on proteins and polysaccharides can potentially be useful for active bio-reactants for biological reactors, so that many biological tissues can be concentrated in the field of tissue engineering with the application as a cell carrier[21].

13) Polymers in swelling controlled system:

Swelling controlled release systems are physically cross-linked as well as chemically cross-linked. Chemically cross-linked are known as hydrogels. Poly (hydroxyethyl methacrylate) which is used in controlled drug release. HPMC is used as Hydrophilic polymer as well as controlled release hydrogel[10,11,16].

14) Polymers in drug conjugates:

It is one of the approach for enhance the delivery of therapeutic agent. The conjugate of polymer and drug composed of drug that is bound covalently to polymer. Approach of polymer drug chain use primarily in the field of cancer remedy which is called as „polymer therapeutics‟. Biodegradable polymer areused while non-biodegradable synthetic polymer such as PEG and poly (hydroxylpropyl methacrylate) mostly used. By direct attachment without spacer is the easiest way of attaching drug to macromolecule. HPMA-doxorubicin and HPMA-paclitaxel undergone in clinical trials[11, 22].

15) Polymers in nanoparticles:

Size of nanoparticles in the range of 10-1000nm. The drug is attached, entrapped and dissolve to polymeric matrix this is occur in nanoparticles drug delivery systems. For sustain drug delivery system polymeric nanoparticles are used. Biodegradable and non-biodegradable polymers are used as a diagnostic agent without delivery devices. These biodegradable polymers fall into nonotoxic and biological active substances. They are useful as a drug in the nanopartal drug delivery system. These biological active substances can be metabolized and removed from the body in the normal metabolic way. Examples of synthetic biodegradable polymers are poly lactoid, poly (lactoid-co-glyolide), poly-ɛ-carolacacton and polanhyridide[23,24,25].

CONCLUSION:

Polymers have various applications in pharmaceutical formulations. Several polymers have been used successfully and others are found as excipients in the design of dosage form. Natural polymers are biocompatible, non toxic, and economical. Polymers are able to enhance drug stability, for controlled release, and improved bioavailabilty. Role of polymers shown in various dosage form such as modified, immediate, extended, and gastroretentive. Polymers are used in various applications based on the basis on type and nature in tableting, capsules, disperse system, drug conjugate, patches, and in nanoparticles.

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Received on 01.03.2019 Modified on 20.03.2019

Res. J. Pharma. Dosage Forms and Tech.2019; 11(2):111-115.

DOI: 10.5958/0975-4377.2019.00017.X