INTRODUCTION:

Design and development of an effective drug delivery system requires ability of the system to deliver active agents at the right place along with right dosage in the body sites for a specific treatment. A good quality drug delivery system requires potentially suitable carriers for enhanced therapeutic actions of drugs molecules within the body. Utilization of polymeric substances in the pharmaceutical industries is growing rapidly because these polymeric materials offers a variety of applications in different biomedical areas for example ophthalmology, implantation of medical devices and artificial organs, dentistry, tissue engineering, bone repair and drug delivery systems etc.^[1]. Polymeric materials are long chain macromolecules, complex structural compositions containing a range of functional groups.

These materials possesses great structural flexibility when combine with different types of low and high molecular-weight materials, they can be modified and can be used for different applications. Natural as well as synthetic polymeric materials are extensively utilized in pharmaceutical drug delivery systems and food products. Depending upon the types, nature and physicochemical properties of polymers being employed in the pharmaceutical dosage forms; polymers play very significant role in development of various types of drug delivery systems. For instance, polymeric materials may be utilized as carriers for controlled release dosage forms, site specific and targeted delivery of active drug molecules, sustained drug delivery, and other types of novel drug delivery systems ^[2]. Selection of suitable polymers for the development of dosage forms is challenging process due to large structural variations in the their structures which directly or indirectly affects the desired chemical, interfacial, mechanical and biological functions. Therefore selection of polymeric materials should be based upon the thorough understanding of the surface and other physicochemical properties of the polymer, extensive in vitro and in vivo studies and specific preclinical tests to prove its clinical safety ^[3].

Because of few constraints associated with synthetic polymers naturally derived polymeric materials provides more superior properties over synthetic materials in terms of their highly defined structural organization at molecular and macroscopic level. Various significant merits offered by natural materials in respect of biocompatibility, excellent biodegradability, low toxicity have attracted different researchers to pay attention towards the widespread application of natural polymers ^[1,3].

Need of Natural Polymers:

· Non-toxicity and Biocompatibility:

Majority of natural products are derived from edible sources which are chemically carbohydrates in nature and composed of repeating monosaccharide units. Hence they are non-toxic in nature.

· Easy availability:

Natural materials are derived from plant and animal sources and they are easily available.

· Biodegradability:

Naturally derived materials provide greater biodegradability property and make them effective carrier for development of targeted drug delivery and other novel systems.

· Economic:

Because raw sources are plants and animals which affects production cost of these materials and make them cheaper in comparison with synthetic polymeric materials.

· Safe and devoid of side effects:

It has been well studied parameters that natural materials have less side and adverse effects of natural materials over synthetic materials which increases patient compliance and public acceptance ^[4].

Natural Polysaccharides:

Natural polysaccharides are economical existing in different structural arrangements, safe with no or less toxicity, high stability, possess desirable hydrophilicity, gel formation abilities make them suitable carriers for the development of solid dosage forms ^[5]. Appropriate growth and development of plants needs essential cell wall components such as protein, carbohydrates and aromatic compounds. Ninety percent of the primary cell walls are made up of carbohydrate and acts as critical component for the proper function of cell wall. Three different types of polysaccharides are used in the makeup of cell walls (cellulose, hemicellulose, or pectin) and pectin is the most abundant material in the plant primary cell walls and. Pectin is a white, high molecular weight, amorphous and colloidal polysaccharide found in ripe fruits, utilized in food products like fruit jellies, cosmetics and pharmaceuticals products due to its emulsification, thickening properties and ability to transformed into a gel like consistency and all these applications make pectin as a suitable biopolymer with enormous potential and possibilities ^[6,7].

Pectin:

Pectins are non starchy linear polysaccharides present abundantly in the plant cell walls. Initially in 1820, pectin was first extracted and isolated and in Germany (1908) first commercial production of liquid pectin extract was recorded, and the process of pectin production was spread speedily to the United States ^[8,9]. Because pectin polymer is obtained from natural sources and offers wide variety of advantages therefore its utilization is increasing very rapidly in the pharmaceutical and biotechnology areas. From many years pectin has been used effectively in the food and beverage industry as a gelling agent, thickening agent, and colloidal stabilizer in different types of products ^[10]. Pectin has an important feature that it has ability to form gel like consistency in aqueous solutions in calcium ions or in presence of a certain amount of sugar and acid. Moreover, pectin can absorb and clear the biogenic toxins, xenobiotics, anabolic steroids, metabolites, and biologically harmful products capable of accumulating in the body. Physicochemical parameters (solubility of pectin and its gelling and film forming properties) of the pectin are strongly affected by the degree of esterification of glacaturonic acid units present within the pectin structure. Processing and harvesting conditions, origin of plant source used for extraction of pectin, isolation, purification, storage and other related factors affects the degree of esterification of pectin structure ^[11,12]. Pectins have the following advantages as additives in food and pharmaceutical products:

· Pectins biopolymer has various properties which make them ideal candidate to be used in drug delivery systems like high stability under acidic conditions even at higher temperature.

· Pectins have unique property of drug encapsulation by gel formation in presence of divalent cations which makes them ideal carriers for delivering therapeutic active drug molecules.

· Pectins have long standing properties of being non-toxic, high availability and low production cost.

· Pectins can be used for administration of active agents by different routes such as orally, nasally, and vaginally etc. ^[13,14].

Sources of Pectin:

Pectin is widely used in the food industry for its gelling and stabilizing properties. It is mainly obtained from plant cell wall particularly from apple pomace, citrus peels, and sugar beet pulps ^[15]. Its maximum concentration is found in the middle lamella of cell wall. Due to diversity in the degree of esterification (DE) and in molecular size, pectin obtained from distinct sources does not have the same gelling ability. Presently, commercial pectins are almost exclusively extracted from apple pomace or peel of citrus fruits (such as orange, lemon and lime), both by-products from juice manufacturing. Based on dry matter basis citrus peel consists of about 20- 30% of pectin while apple pomace consists of 10-15% of pectin. Various other sources are also available from which pectin is obtained by adding dilute mineral acids at pH about 2 which includes mango waste, legumes, sugar beet waste from sugar production, banana, cabbage, pomelo peel and carrots etc. Further the extract obtained is clarified via filtration process using a filter aid. The clarified extract obtained is then concentrated in vacuum and the pectin precipitated by adding ethanol or isopropanol. Low-esterified pectins were obtained when the initial pectin is treated with dilute acids. Also amidated pectins are obtained when the above process comprises of ammonium hydroxide. After drying and milling, pectin is usually standardized with sugar and sometimes calcium salts or organic acids to have optimum performance in a particular application ^[16,17]. Different research studies have been conducted for extraction of pectin on different sources of pectin as represented in Table 1.

Table 1: Different research studies on various sources of Pectin (Percentage yield)

Source of Pectin	Percentage yield %	References
Apple pomace	18.79	Kumar et al^[18]
Pineapple	0.8	Ukiwe et al^[19]
Fruit peels	7.23	Sotanaphum et al^[20]
Dragon fruit	20.14	Ismail et al^[21]
Lemon peels	1.583	Salam et al^[22]
Orange and Lemon peels	2.95 3.15	Georgiev et al^[23]
Orange peels	46.26	Pandharipande et al^[24]
Cocoa husks	7.62	Chan et al^[25]
Aloe vera	5.77	Gentilini et al^[26]
Passion fruit peels	14.60	Liew et al^[27]
Orange peels	36.71	Kanmani et al^[28]
Grapefruit	22.55	Khan et al^[29]
Papaya fruit	16	Altaf et al^[30]
Black mulberry	14.47	Mosayebi et al^[31]
Orange peels Grapefruit peels	25.92 33.63	Sayah et al^[32]
Passion fruit peels	7.16	Liew et al^[33]
Banana peels Mango peels	11.31 18.5	Girma et al^[34]

Classification of Pectins

Pectins are broadly divided according to the degree of methoxylation (DM) as high methoxyl and low methoxyl pectins. The degree of methoxylation is represented as a percentage of esterified galacturonic acid units to total galacturonic acid units in the molecule of pectin.

1) Pectins are classified as high methoxyl (HM) pectin when it is formed by normal extraction procedure consisting of more than 50% of methoxyl groups. These high methoxyl (HM) pectins are able to form gels in aqueous systems with low pH values 7 and high contents of soluble solids.

2) In contrast to above, conventional low methoxy (LMC) pectins were formed by alteration of extraction methods, or with continued acid treatment having lower than 50% methoxyl groups. These pectins in presence of bivalent salts usually Ca²⁺ ions are capable of forming gels in system having vast pH range 7 and low solids content.

3) During fabrication pectins can be treated with ammonia in order to yield amidated low methoxy (LMA) pectin having less than 50% methoxyl groups and from 5 to 25% of amidated groups ^[35].

Chemical structure of Pectin

· Pectin is a naturally occurring polysaccharide. Alike other plant polysaccharides, it is polydisperse and polymolecular in nature and during isolation its composition differ with the conditions and source used. Pectin can modify during isolation from plants, processing of plant material and during storage, so its structures is difficult to determine. It is composed of D-galacturonic acid (GalA) units [5], which are joined in chains by means of a-(1-4) glycosidic linkage. Further these uronic acids consists of carboxyl groups, some of which are present naturally as methylated esters while others are treated commercially with ammonia to yield carboxamide groups (Figure 1) ^[36,37].

Figure 1: Chemical structure of Pectin

Pharmaceutical uses of Pectin:

Pectin appeared as a promising bipolymer in pharmaceutical industry. It acts as a natural preventive substance in addition with toxic cations against poisoning, also reduces the blood cholesterol levels. Further it also has significance in gastrointestinal and respiratory disorders. It has also been reported to be effective in regulating local bleeding or hemorrhage by reducing the coagulation time of drawn blood when given intravenously. Also pectin in combination with other colloids have been used largely to treat diarrheal conditions in children and infants. Some results also indicated antimicrobial action of pectin against Escherichia coli. under certain in vitro conditions. Pectin also resulted in lower absorption of food by immobilizing food constituents in the intestine thus reducing the rate of digestion. Also it has a wide water-binding capacity which results in a sense of satiety and hence reduces food consumption^[11]. Pectin has promising pharmaceutical uses such as in controlled release dosage forms, it acts as a carrier and a number of techniques such as ionotropic gelation and gel coating have been used to fabricate the pectin based delivery systems. Along with the above techniques used, also having very safe toxicity profile, it makes pectin an interesting and promising excipient for the pharmaceutical industry for present and future purposes ^[18]. Pectin hydrogels have been reported to act as binding agents in controlled-release matrix tablet formulations ^[10]. Also it acts as an encapsulating agent in sustained release dosage forms alone or in combination with gelatin. Further low methoxy pectin in combination with aluminium hydroxide and magnesium oxide has been found to be effective in treating duodenal and gastric ulcers. Also HM pectin during its administration act as a demulcent and reduces the gastric irritation and hence improves the sustained release action of aspirin ^[11,37].

CONCLUSION:

Pectin has been reported for its potential in pharmaceutical industry, analysis and health exaltation based on its chemistry and gel-forming mechanisms. It has been found that valuable and large grades of pectin can be obtained from major sources rather than numerous natural sources. Apart from its utilization in sustained release, pectin has been extensively used in pharmaceutical preparations and formulation of drugs as a carrier for a vast variety of biologically active agents. Numerous dosage forms of different morphology and characterstics can be formulated using appropriate form of pectin, gelation conditions, coating agents and added excipients. Several advancements of significant values have been invented for the elucidation of chemical structure, biological action and physiochemical properties of pectin. The successful application of pectin in various delivery systems points the way for its future development.

CONFLICT OF INTEREST:

Authors do not have any conflict of interest

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Received on 29.12.2016 Modified on 18.02.2017

Research J. Pharm. and Tech. 2017; 10(4): 1225-1229.

DOI: 10.5958/0974-360X.2017.00219.0