Preparation of disintegration tablet using Cucurbita maxima pulp powder as disintegration

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About Authors:
Madhu  dwivedi, Rishabha Malviya
Department of pharmaceutical technology
MIET,MEERUT

Introduction:
Natural polymer: A number of natural or partially modified polymers were screened for mucoadhesive properties by routinely measuring the force of detachment for swollen polymer films from pig intestinal mucosa in a saline medium. Suprisingly, hydroxypropyl- and carboxymethylcellulose showed almost no mucoadhesion, whereas the cationic polymer chitosan was fairly mucoadhesive in comparison to Polycarbophil as a reference substance. It is suggested that a strict difference be made between mucoadhesion of dry polymers on a wet tissue in air, and mucoadhesion of a swollen hydrogel in the presence of a third liquid phase. Cationic polymers should be further investigated with respect to possibly improved mucoadhesive properties in a neutral or slightly alkaline environment.

Reference Id: PHARMATUTOR-ART-1217

Natural polymers are obtained in the form of macromolecules. The natural polymers demands in the households, agriculture, food industries and in packaging and it also help in reducing the environmental pollution and resulting in disposal in landfills. Natural polymers are act as an environment cleaner, renewable and help in recycling of global carbon. The natural gums are biodegradable, nontoxic and biocompatible in nature and swells when comes in contact with the aqueous media so it has been used in the preparation of sustained release or controlled release types of dosage form. In the present investigation it shows that plant polysaccharide have been useful for the construction of specific drug delivery systems.[1]The polysaccharide that is present in natural polymer is known as tamarind seed polysaccharide Gum is present in the tamarind seed and it is a hydrophilic polymer and had been used as gelling, thickening, suspending and emulsifying agents.[2,3,4,5] Gum consisted 65% of the seed components.[6,7,8] It is used as a thickening, stabilizing and gelling agents in food.[9]The gum can also be act as a binder in pharmaceutical tablets, as a humectants and emulsifier in the different types of formulations.[10] This shows that the Natural polymer is highly viscous, mucoadhesive and biocompatible in nature. Now the regular research is going on in field of natural occurring biocompatible polymeric material in designing of dosage form for oral controlled release administration. The Natural polymer has a widest scope in the pharmaceutical industries and it is act as a binder in tablet dosage form, ocular drug delivery system and in sustained release drug delivery systems. It is a novel mucoadhesive polymer, can be used in the delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics[11] Polysaccharides are a class of biopolymers constituted by simple sugar monomers [12]. The monomers (monosaccharides) are linked together by O-glycosidic bonds that can be made to any of the hydroxyl groups of a monosaccharide, conferring polysaccharides the ability to form both linear and branched polymers. Differences in the monosaccharide composition, chain shapes and molecular weight dictate their physical properties including solubility, gelation and surface properties. These biological polymers can be obtained from different sources: microbial, animal and vegetal [13]. Several advantages can be derived from the use of these macromolecules. First of all, probably because of the chemical similarities with heparin, polysaccharides show good hemocompatibility properties. They are non-toxic, show interaction with living cells and, with few exceptions, have low costs in comparison with others biopolymers such as collagen [13] and [14]. These polysaccharidic polymers have been widely proposed as scaffold materials in tissue engineering applications as well as carriers for drug delivery systems as described in more detail in the following sections.

Collagen:Collagenis regarded by many as an ideal scaffold or matrix for tissue engineering as it is the major protein component of the extracellular matrix, providing support to connective tissues such as skin, tendons, bones, cartilage, blood vessels, and ligaments[6], [7], [8], [9] and [10]. In its native environment, collagen interacts with cells in connective tissues and transduces essential signals for the regulation of cell anchorage, migration, proliferation, differentiation, and survival. [11]Twenty-seven types of collagens have been identified to date, but collagen type I is the most abundant and the most investigated for biomedical applications. The different collagens are first synthesized as large precursor molecules known as procollagens [15]. After secretion of procollagen into the extracellular matrix, both C- and N-propeptides are cleaved and the molecules then self-assemble into fibrils (a detailed review can be found in [11]. Fibril-forming collagen molecules used in tissue engineering applications consist of three polypeptide chains of glycine-X-Y (Gly-X-Y) amino acid repeats twined around one another to form triple helices [16] and [17].

Gelatin: Gelatin is a natural polymer that is derived from collagen, and is commonly used for pharmaceutical and medical applications because of its biodegradability and biocompatibility in physiological environments as reviewed by Tabata and Mikos [18]and [19]. These characteristics have contributed to gelatin's safety as a component in drug formulations or as a sealant for vascular prostheses. [20]Moreover, gelatin has relatively low antigenicity because of being denatured in contrast to collagen which is known to have antigenicity due to its animal origin. Gelatin contains a large number of glycine, proline and 4-hydroxyproline residues.
Gelatin is a denatured protein obtained by acid and alkaline processing of collagen. As a result, two different types of gelatin can be produced depending on the method in which collagen is pre-treated, prior to the extraction process [20]. This pre-treatment affects also the electrical nature of collagen, producing gelatin with different isoelectric points. The alkaline process targets the amide groups of asparagine and glutamine and hydrolyses them into carboxyl groups, thus converting many of these residues to aspartate and glutamate. In contrast, acidic pre-treatment does little to affect the amide groups present. The result is that gelatin processed with an alkaline pre-treatment is electrically different from acidic-processed gelatin. This is due to hydrolysis of amide groups of collagen yields gelatin with a higher density of carboxyl groups present in the alkaline processed gelatin rendering it negatively charge and lowering its isoelectric point [18]. In contrast, the electrostatic nature of collagen is hardly modified through the acid process because of a less invasive reaction to amide groups of collagen. As a result, the isoelectric point of gelatin that is obtained with the acid process will remain similar to that of collagen [19]. By utilizing this technique, manufacturers now offer gelatin in a variety.

Silk fibroin: Silk is generally defined as protein polymers that are spun into fibers by some lepidoptera larvae such as silkworms, spiders, scorpions, mites and flies [21]. Spider silk is an intriguing biomaterial that is lightweight, extremely strong and elastic, and exhibits mechanical properties comparable to the best synthetic fibers produced by modern technology[22]. Spider silk is spun near ambient temperatures and pressures using water as the solvent, which gives rise to an environmentally safe, biodegradable material [22]. However, it is not possible to maintain domesticated spiders to produce massive amounts of silk. Therefore, the attention was turned to silk fibroin, a mass-producible natural polymer produced by silkworms, commonly used as a textile fiber. In the medical field, silk has long been used for surgical sutures [23].

Fibrin: Fibrin and fibrinogen have a well-established application in research in tissue engineering due to their innate ability to induce improved cellular interaction and subsequent scaffold remodelling compared to synthetic scaffolds. Furthermore, due to its biochemical characteristics, mainly in cellular interactions, fibrin-based materials also found applications in the field of drug delivery with special focus in cell delivery.

Chitosan: Chitosan is a cationic polymer obtained from chitin comprising copolymers of β(1→4)-glucosamine and N-acetyl-d-glucosamine. Chitin is a natural polysaccharide found particularly in the shell of crustacean, cuticles of insects and cell walls of fungi and is the second most abundant polymerized carbon found in nature. Chitosan, the fully or partially deacetylated form of chitin, due to its properties as attracted much attention in the tissue engineering and drug delivery fields with a wide variety of applications ranging from skin, bone, cartilage and vascular grafts to substrates for mammalian cell culture. It has been proved to be biologically renewable, biodegradable, biocompatible, non-antigenic, non-toxic and biofunctional[24].

Starch: Starch is one of the most promising natural polymers because of its inherent biodegradability, overwhelming abundance and renewability. It is composed of a mixture of glycans that plants synthesize and deposited in the chloroplasts as their principal food reserve. Starch is stored as insoluble granules composed of α-amylose (20–30%) and amylopectin (70–80%)[25]. α-Amylose is a linear polymer of several thousands of glucose residues linked by α(1→4) bonds. The α-glycosidic bonds of α-amylose cause it to adopt an helical conformation (left-handed helix) [25]. Amylopectin consists mainly of α(1→4)-linked glucose residues but it is a branched molecule with α(1→6) branch points every 24 to 30 glucose residues in average.
Amylopectin molecules contain up to 106 glucose residues, making them some of the largest molecules in nature [25]. Starch by itself is extremely difficult to process and is brittle when used without the addition of a plasticizer. In most applications, the semi-crystalline native starch granule structure is either destroyed or reorganized, or both [26]. Water is the usual plasticizer in starch processing, and the physical properties of starch are greatly influenced by the amount of water present [26]. Therefore, the use of other plasticizers, such as low molecular weight alcohols, especially for the production of thermoplastic starches, renders starch more processable [26]. Additionally, blending two or more chemically and physically dissimilar natural polymers has shown potential to overcome these difficulties. Over the years several materials have been blended with starch to improve its processability, including, but not restricted to, several synthetic polymers, such as polyethylene [27], polycaprolactone[28].

Alginate: Alginate is one of the most studied and applied polysaccharidic polymers in tissue engineering and drug delivery field. They are abundant in nature and are found as structural components of marine brown algae and as capsular polysaccharides in some soil bacteria. Commercial alginates are extracted from three species of brown algae. These include Laminaria hyperborean, Ascophyllum nodosum, and Macrocystis pyrifera in which alginate comprises up to 40% of the dry weight [29]. Bacterial alginates have also been isolated from Azotobacter vinelandii and several Pseudomonas species [29]. Alginates are naturally derived polysaccharide block copolymers composed of regions of sequential β-d-mannuronic acid monomers (M-blocks), regions of α-l-guluronic acid (G-blocks), and regions of interspersed M and G units [30]. The length of the M- and G-blocks and sequential distribution along the polymer chain varies depending on the source of the alginate. Alginates undergo reversible gelation in aqueous solution under mild conditions through interaction with divalent-cations such as Ca2+ that can cooperatively bind between the G-blocks of adjacent alginate chains creating ionic inter-chain bridges. This gentle property has led to their wide use as cell transplantation vehicles to grow new tissues and as wound dressings. Moreover, alginate as an anionic polymer with carboxyl end groups is a good mucoadhesive agent [29].

Dextran: Dextran is a branched, high molecular weight polymer of d-glucose, produced by different bacterial strains from sucrose via the action of dextransucrase enzyme [31], consisting of α(1→6)-linked d-glucose residues with some degree of branching via α(1→3) linkages. Dextran is readily available in a wide range of molecular weights along with several derivatives and it is biodegradable and biocompatible. These properties make it suitable for a whole range of applications, such as plasma-expanders and blood substitutes, since it binds to erythrocytes, platelets and vascular endothelium by reducing their aggregation and adhesiveness, respectively. Additionally, it has also been shown to be a bone healing promoter and also for dermal and subcutaneous augmentation and for drug delivery [13].

Polyhydroxyalkanoates: In nature, a special group of polyesters is produced by a wide variety of microorganisms as an internal carbon and energy storage, as part of their survival mechanism  Poly(β-hydroxybutyrate) (PHB) was first mentioned in the scientific literature as early as 1901.

Advantages of natural polymers:
The various advantages of natural plant base materials include:
1. Biodegradable:Biodegradable is the naturally available; they are produced byall living organisms.
2. Biocompatible and non-toxic: Basically, all of these plant materials are repeating sugar polysaccharides.
3. Low cost: cheaper to use as natural sources. the production cost is less compared with the synthetic material. In India and many other developing countries are dependent on agriculture and they are large amount of money investment on agricultures.
4. Environmental-friendly processing: There are many types of natural compounds obtained from different plant sources which are widely used in pharmaceutical industry and collected in large quantities due to the simple production processes involved.
5. Local availability (especially in developing countries): In India and similar developing countries, there is promotion for the production of plants as pharmaceutical excipients being done by government and it also provide the facilities for bulk production, like gum and mucilages because of there wide applications in industries.
6. They have better patient tolerance as well as public acceptance: There is less chance of side and adverse effects with natural materials compared with synthetic one. For example, povidone.

Disadvantages of natural polymer
1. Often antigenestic or rejection system.
2. Prediction at degradation rate is difficult.
3. Poor strength due to water absorption.
4. Questionable purity and high cost.

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