INTRODUCTION:

Years ago, before there were plastics and synthetic polymers, in fact, all the way back to the beginning of the earth, nature was using natural polymers to make life possible. Polymers are the backbone of a transdermal drug delivery system as they control the release of the drug from the device. Natural polymers can be used as the means of achieving predetermined rates of drug delivery and their physicochemical characteristics with the ease of availability provide a platform to use it as a polymer for transdermal drug delivery system. These polymers may be used to formulate various controlled and targeted drug delivery system. Depending upon the polymer, the environmental change can involve pH, temperature or ionic strength and the system can either shrink or swell upon a change in any of these environmental factors of these sensitive systems. Drug release is accomplished only when the polymer swells and because many of the potentially most useful pH sensitive polymers swell at high pH values and collapse at low pH values, triggered drug delivery occurs upon an increase in the pH of the environment. Such materials are ideal for systems such as oral delivery, in which the drug is not released at low pH values in the stomach, but rather at high pH values in the upper small intestine ^{[1, 6]}.

Polymers

A polymer is a large molecule (macromolecule) composed of repeating structural units or chains typically connected by covalent chemical bonds. While polymer in popular usage suggests plastic, the term actually refers to a large class of natural and synthetic materials with a variety of properties and purposes.

Polymers may consist of long chains of unbranched or branched monomers or may be cross-linked networks of monomers in two or three dimensions.

Many important natural materials are organic polymers including cellulose, lignin, rubber, proteins and nucleic acids. Synthetic organic polymers many plastics, including polyethylene, the nylons, polyurethanes, polyesters, vinyl’s (e.g., PVC), and synthetic rubbers. The silicone polymers, with an inorganic backbone of silicon and oxygen atoms and organic side groups, are among the most important mixed organic-inorganic compounds ^[1,
8].

Polymer properties

Extensive applications of polymers in drug delivery have been realized because polymers offer unique properties which so far have not been attained by any other materials. Various natural gums and mucilage’s have been examined as polymers for control and sustained drug release, in the last few decades.

Natural polymers remain attractive primarily because they are commercial, readily available, capable of multitude of chemical modifications, potentially degradable and compatible due to their origin.

The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways

Polymers are macromolecules having very large chains, contain a variety of functional groups, can be blended with other low and high–molecular weight materials, and can be tailored for any applications.

Protein, enzymes, muscle fibers, polysaccharides and gummy exudates are the natural polymers being used effectively in formulating the variety of pharmaceutical products. The well known natural polymers used in pharmacy and other fields are alginates, chitosan, carrageenan, isapghula, acacia, agar, gelatin, guar gum. These natural polymers are widely used in pharmaceutical industry as emulsifying agent, adjuvant and adhesive in packaging; and also well suited for pharmaceutical and cosmetic product development. Natural polymers obtained from gummy exudates and plant fibers are being discussed here to take a closer look at their applications in pharmacy and other fields ^{[2, 8, 9, 12]}.

Classification of Polymers:

Polymers may be classified as follows, according to the mechanical response at elevated temperatures

1. Thermoplasts

2. Thermosets

a) Thermoplasts:

· Thermoset polymers soften when heated and harden when cooled. Simultaneous application of heat and pressure is required to fabricate these materials.

· On the molecular level, when the temperature is raised, secondary bonding forces are diminished so that the relative movement of adjacent chains is facilitated when a stress is applied.

· Most linear polymers and those having branched structures with flexible chains are thermoplastics.

· Thermoplastics are very soft and ductile.

The commercial available thermoplasts are

· Polyvinyl Chloride (PVC) and Polystyrene

· Polymethyl methacrylate

· Polystyrene^[2].

b) Thermosets:

· Thermosetting polymers become soft during their first heating and become permanently hard when cooled. They do not soften during subsequent heating. Hence, they cannot be remolded/reshaped by subsequent heating.

· In thermosets, during the initial heating, covalent cross-links are formed between adjacent molecular chains. These bonds anchor the chains together to resist the vibration and rotational chain motions at high temperatures. Cross linking is usually extensive in that 10 to 15% of the chains per units are cross linked. Only heating to excessive temperatures will cause severance of these crosslink bonds and polymer degradation.

· Thermoset polymers are harder, stronger and more brittle than thermoplastics and have better dimensional stability.

· They are more usable in processes requiring high temperatures

· Most of the cross linked and network polymers which include,

o Vulcanized rubbers

o Epoxies

o Phenolic

o Polyester resins

· Thermosets cannot be recycle, do not melt, are usable at higher temperatures than thermoplastics, and are more chemically inert ^[2,
15].

· Also polymers can be classified as,

1. Natural polymers

2. Synthetic polymers

3. Semi-synthetic polymers

(i) Natural polymers:

The polymers obtained from nature (plants and animals) are called natural polymers. These polymers are very essential for life. They are as follows:

(a) Starch: It is polymer of glucose and it is food reserve of plant.

(b) Cellulose: It is also a polymer of glucose. It is a chief structural material of the plant both starch and cellulose are made by plants from glucose produced during photosynthesis.

(c) Proteins: These are polymers of α-amino acids; they have generally 20 to 1000 α-amino acid joined together in a highly organized arrangement. These are building blocks of animal body and constitute an essential part of our food.

(d) Nucleic acids: These are polymers of various nucleotides. For example RNA and DNA are common nucleotides. It may be noted that polymers such as polysaccharides (starch, cellulose), proteins and nucleic acids etc. which control various life processes in plants and animals are also called biopolymers ^{[2, 4, 11]}.

(ii) Synthetic polymers: The polymers which are prepared in the laboratories are called synthetic polymers. These are also called man made polymers. For example polyethene, PVC nylon, teflon, bakelite terylene, synthetic rubber etc ^[2].

(iii) Semi synthetic polymers: These polymers are mostly derived from naturally occurring polymers by chemical modifications. For example cellulose is naturally occurring polymers, cellulose on acetylation with acetic anhydride in the presence of sulphuric acid forms cellulose diacetate polymers. It is used in making thread and materials like films glasses etc. Vulcanized rubber is also an example of semi synthetic polymers used in making tyres etc. gun cotton which is cellulose nitrate used in making explosive ^{[2, 10]}.

Natural polymers used in formulations:

Carrageenan

Carrageenan is the hydrocolloid obtained from red seaweeds by extraction with water or aqueous alkali and recovered by alcoholic precipitation, drum drying or freezing (Class: Rhodophyceae). It consists of a mixture of the ammonium, calcium, magnesium, potassium and sodium sulphate esters of galactose and 3, 6-anhydrogalactosecopolymers. It is widely used as dissolution rate retarding polymer in sustained release dosage form in many pharmaceutical industries. Solution of carrageenan (1%) was also used to induce inflammation (Paw oedema) for screening of anti- inflammatory activity. Carrageenan is used in pharmacy and food industry as a suspending and gelling agent. Tooth paste, creams, lotions and other cosmetic products are also prepared by using carrageenan. In food industry, it is utilized in milk products, ice creams, chocolate, jams and gels in the concentration of 0.5-1%^{[2, 3, 5, 6]}.

Ispaghula

Ispaghula husk consist of dried seeds of the plant Plantago ovate Forsk. (Family⎯Plantaginaceae) commonly has known as Isabgolor Ispaghula or Spogel seeds. It contains mucilage, which is present in the epidermis of seeds. Larger doses are essential as their action is produced partly by lubricating action of mucilage and partly by the increase in bulk of intestinal contents, which mechanically stimulates the intestinal peristalsis. Mucilage is used as binding agent in the granulation of material for preparation of compressed tablets. It is used as a suspending and thickening agent due to its high swelling factor and ability to give a uniform viscous solution. It is much sought in pharmaceutical industry as enteric coating material, tablet disintegrator and also used in sustained release drug formulations ^{[2, 6]}.

Acacia

The air dried gummy exudates from the stem and branches of Acacia senegal Willd. (Family ⎯ Mimosaceae) and other species of acacia of African origin. It also known as senegal gum. The tree is known in kordofan as ‘Hashab’ and in senegambia as ‘Verek’. The gum, produced in kordofan from tapped trees is considered to be good. The senegal and nigerian gum is also of good quality. The senegal gum is available in the desert areas of India like Rajasthan, Gujarat and Haryana. It is soluble in water leaving only a very small residue of vegetable particles, whereas practically insoluble in alcohol and ether ^{[2, 6]}.

Agar

Agar-Agar, also known as Japanese Isinglass, Chinese-Isinglass or Vegetable Gelatin. It is the dried, hydrophilic and phycocolloidal concentrate from a decoction of various marine red algae, particularly species of Gelidium (Gelidaceae), Pterocladi (Gelidaceae), order Gelidiales and Gracilaria (Gracilariaceae). The dried Agar-Agar usually occurs in bundles comprising thin, membranous, agglutinated strips; or in cut, flaked or granulated forms. It may be weak yellowish orange, yellowish grey to pale yellow or colorless. It is tough when damp, brittle when dry, odorless or with a slight odour and has mucilaginous taste. The Agar-Agar is insoluble in cold water, but soluble in boiling water. Agar contains two different polysaccharides named as agarose and agaropectin. Agarose is responsible for gel strength of agar and composed of D-galactose and 3, 6-anhydro-L-galactose units^{[2, 6, 13, 14]}.

Gelatin

Gelatin is a natural water-soluble macromolecule resulting from the heat dissolution and partial hydrolysis of collagen. There are two types of gelatin: type-A gelatin is obtained by acid treatment of collagen with the isoelectric point between 7.0 and 9.0, whereas Type-B gelatin is produced via alkaline hydrolysis of collagen with the pH between 4.8 and 5.0. Gelatin offers a number of advantages over other synthetic polymers including non-irritability, biocompatibility and biodegradability, which makes it one of the desirable materials as carrier molecule. It is a natural macromolecule which is non-toxic and non-carcinogenic, and it shows low immunogenicity and antigenicity. Gelatin has large number of functional groups on its surface which aid in chemical cross-linking and derivatization. These advantages led to its application for the synthesis of nanoparticles for drug delivery during the last thirty years ^{[2, 3, 5, 6]}.

Xanthan gum

This gum is produced by a pure culture fermentation of a carbohydrate with Xanthomonas campestris and purified. It is also known as Corn sugar gum. It is the sodium, potassium or calcium salt of a high molecular weight polysaccharide containing D-glucose, D-mannose and D-glucuronic acid. It also contains not less that 1.5% of pyruvic acid. It is a cream coloured powder, soluble in hot and cold water. A 1% solution has viscosity of about 1000 centipoises. Solutions of xanthan gum demonstrate maximum stability at pH value between 4 and 10. Compared with tragacanth, xanthan gum was found to be easier to use and capable of preparing suspensions of better quality and improved consistency. Xanthan gum is used as a stabilizer, thickener and emulsifier extensively in pharmaceutical, cosmetic industries and in food industry for dairy products. The pseudo plastic properties of this gum enable toothpastes and ointments both to hold their shape and to spread readily. The stability was generally good and few drugs had been found to be incompatible (Amitriptyline, Tamoxifen and Verapamil). For extemporaneous dispensing, a 1% solution of xanthan gum with hydroxybenzoate, prepared in advance, was diluted to 0.5% with water when preparing the suspension. Xanthan gum was found to be suitable suspending vehicle for delivering antispasmodics topically along the length of the esophagus in patients with esophageal spasm. Coagulation of the gum had been observed when it was used for suspension of certain film coated tablets. Sedimentation volume of suspension with Carboxy methyl cellulose and xanthan gum, keep for period of 45 days. Results indicated that xanthan gum in a concentration of 0.2% is superior to Carboxy methyl cellulose ^{[2, 3, 5-7]}.

CONCLUSION:

The Polymers are used to control the drug release rate from the formulations. Extensive applications of polymers in drug delivery have been realized because polymers offer unique properties which so far have not been attained by any other materials. Various natural gums and mucilage’s have been examined as polymers for control and sustained drug release, in the last few decades. Natural polymers remain attractive primarily because they are commercial, readily available, capable of multitude of chemical modifications, potentially degradable and compatible due to their origin. Now-a-days natural polymers play a very important role almost in all kind of formulations. The pharmaceutical scientists have achieved a great success in developing the most therapeutic systems with suitable natural polymers. Despite the excessive use of synthetic polymers the need for natural biodegradable polymers to deliver drugs continues to be area of active research. Design and synthesis of novel combinations of polymers will expand the scope of new drug delivery systems in the future.

REFERENCES:

1. Evans WC, Trease and Evans. Pharmacognosy, Harcourt Brace and co. Asian Pvt. Ltd. 14^thedition, 1996:196, 208,209,213,215,462,555.

2. Kokate CK, Purohit AP, Gokhale SB. Pharmacognosy, 22^nd edition Nirali Prakashan Pune, 2005 :136, 147,148,150,152-154,157,441.

3. Manjanna KM, Pramodkumar TM, Shivakumar B. Natural polysaccharide hydrogels as novel excipients for modified drug delivery system. Industrial journal of chem. tech research. Vol.1. 2010: 509-525.

4. Jae Hyung Park, Mingli Ye and Kinam park.Biodegradable polymers for microencapsulation of drugs 2005. Vol-10:146-161.

5. Sharma Kiran, Singh Vijender, Arora Alka. Natural biodegradable polymers as Matrices in Transdermal drug delivery Vol-3. International journal of drug development and Research. 2011: 85-103.

6. T. Satapathy, PK. Panda BN, Tripathy, B. Meher, SP Tiwari, TK Mohapatra. Natural polymers in drug delivery. International journal of universal pharmacy & life science. 2011: 2249-6793.

7. Cohan, Wendy. "Could Xanthan Gum Sensitivity be Complicating your Celiac Disease Recovery?" Celiac.com. Retrieved 2010:05-19 .

8. Indian Materia Medica, by Nadkarni KM. Popular Prakashan, Bombay, 3^rdeddion, 1, revised and enlarged by Nadkarni AK.1976:981-982.

9. Varro E Tyler, Lynn R Brady & james E Robbers. Pharmacognosy, 8^theddition, lea and Febiger, Philadelphia. 1981:47, 50-51, 53,295.

10. Guo J, Skinner GW, Harcum WW, Barnum PE. Pharmaceutical applications of naturally occurring water-soluble polymers.1988.Vol-1.:254-261.

11. Kulkarni GT, Gowthamarajan K, Dhobe RR, Yohanan F, Suresh B. Development of controlled release spheriods usingnatural polysaccharide as release modifier drug delivery. 2005. Vol-1.:12, 201-206.

12. Tommasina Coviello., Scleroglucan. Versatile polysaccharide for modified drug delivery; Molecules; 2005: 6-33.

13. Agar-Agar at Agar-Agar.org

14. Agar-Agar at Botanical.com

15. Substance Info (and synonyms): Xanthan gum. All Allergy. Retrieved 2010-05-19

Received on 21.09.2013 Modified on 23.10.2013

Res. J. Pharm. Dosage Form. & Tech. 6(1): Jan.-Mar. 2014; Page 54-57