International Journal of Drug Development and Research

Key words

Natural polymers, superdisintegrant, binder, renewable, biodegradable.

INTRODUCTION

Fast disintegrating tablets are very popular now-adays as they get dissolved or easily disintegrated in mouth with in few seconds of administration without the need of water1. Active drug is released immediately from the tablet when is placed on the tongue2-5. This formulation is convenient for the patients suffering from Dysphagia. FDTs have several advantages over solid and liquid dosage form like these are very easy to handle as it is a solid dosage form it can be easily transported from one place to another, They are easily administered as it is a unit dosage form and do not need water to swallow they are taken anywhere at any time and also during travelling for motion sickness. In case of FDTs there is no risk of suffocation as it does not need water to swallow and there is no chance of sticking of tablet in the mouth, FDTs have more bioavailability than conventional tablets because when it is placed in the mouth it gets easily dissolved in the saliva, absorbed in the oral cavity and release the active drug with in few seconds increasing the bioavailability of the tablet, FDTs have quick onset of action as its absorption is very fast with in few secounds, FDTs are better in taste and hence the palatability of the tablet is improved, it also improve the patient compliance6.

The polymers obtained from the natural origion are more effective and safe. They are easily available in natural regions around the world therefore they are preferred over synthetic poymers7. Natural polymers are used in most of the prepration and are more advantageous over synthetic polymers as they are economical they have low cost and are easily available in the sufficient quantity, natural polymers are non toxic they do not have any harmful effects on the body, Natural polymers are enviornmental friendly as they are biodegradable in nature they do not cause any pollution, natural polymers are devoid of side effects as they are obtained from the natural source, natural polymers are mainly preferred by the patients as they are more safe and effective as compared to the synthetic polymers and have more patient compliance, natural polymers provide nutitional supplement and are renewable as they are used again and again in different reactions8. Synthetic polymers have certain drawbacks viz high cost because they are prepared by different procedures or reactions by using costly instruments and equipments and it require a lot of time to form a synthetic polymer. Synthetic polymers are non renewable sources as they are not used again and again, they have more side effects as they are prepared by different reactions using different chemicals which can interact with the body components sometimes body can consider it as a foreign matter and cause allergic reactions in the body, they can cause toxicity in the body, synthetic polymer cause enviornmental pollution during their synthesis, synthetic polymers are non-biodegradable (biodegradable synthetic polymers are costlier) and patients generally do not prefer synthetic polymers because of they side effects so these are less patient compliant.

The aim of this review is to study different natural polymers and their pharmaceutical action which are used in fast disolving tablets, and comparision of the properties of tablet improved by using natural polymers over synthetic polymers. Natural polymers improve the tablet properties in the fast dissolving tablets like disintegration time the tablet get disintegrated fastly within few secounds because of the use of superdisintegrant as natural polymer like Lallemantia reylene seed mucilage, mangifera indica gum, dehydrated banana powder etc., they increase the porosity of the granules so that the tablet formed is easily get dissolved in the mouth without the use of water, the drug get rapidly released from the tablet by the action of natural polymer, natural polymer like Modified Aegle Marmelos gum can increase the solubility of poorly water soluble drug like Aceclofenac, Natural polymers have appreciable efects on hardness and friability.

FAST DISOLVING TABLETS

Fast dissolving tablets (FDTs) are the novel dosage form. These are the tablets that dissolve with in few secounds in the mouth when come in contact with the saliva without the need of water9. This dosage form improve patient compliance and mostly preferred by geriatric and pediatric patients with poor physiological and physical abilities and also by the travelling patients suffered from motion sickness FDTs are very effective in such situation as it dissolved rapidly in mouth and have quick action.

FDTs are also called fast disintegrated, mouth dissolving, fast melts, rapid melts and orodisperable tablets. It is mostly preferred by the patients who feel difficulty in swallowing (Dysphagia).10

Ideal properties of FDTs

•It should be quickly disintegrated with in secounds when placed in mouth.

•It should not require water to dissolve.

•Being a unit dosage form it should provide accurate dosing.

•Quick dissolution and absorption in the oral cavity.

•Easy to transport.

•Tablets are manufactured with conventional equipment with in low cost.

•Less sensitive to enviornmental condition like humidity and temperature.

•It should less fragile and should maintain its hardness.

Advantages of FDTs

•FDTs are solid unit dosage form, so it provide accurate dosing, high drug loading is allowed in it, and it is an ideal dosage in case of geriatric and pediatric patients and also it is an ideal alternative of conventional tablet.

•It has fast action, as it is taken by the patient it gets starts melting when it come in contact with saliva it rapidly absorbed in the oral cavity, it rapidly melts and produce quick action.

•Due to pregastric absorption the bioavailability of the drugs is improved, and less dose is required, which improves the patient compliance, clinical reports is also improved.

•FDTs does not require water to swallow and also it can be taken anywhere at anytime, it is a convenient option for travelling patients and busy peoples who do not have immediate access of water hence patient compliance is improved.

•It is very easy and convenient to administer as it is a solid unit dosage form, it is mainly convenient for geriatric, pediatric uncooperative patients and dysphagic patients.

•FDTs are very safe and easy to swallow because there is no risk of suffocation in the airways due to physical obstruction during swallowing.

•FDTs contain leaves minimal and it completely dissolve in the mouth no residue is left so provide good mouth feel hence improved palatability of the tablet.

•FDTs are less sensitive to enviornmental condition hence they are very stable.

•FDTs are packed in simple blister packaging and there is no need of special and costly packaging, so that they are economical.

•FDTs provide new buissness avenues as prouct differenciation, product promotion, line extension, uniqueness, and life cycle management.

•FDTs are cost effective it does not require costly ingradients, natural polymers when used as excipient are available easily and at low cost and also it does not require special packaging material it can be packed in simple blister packs.

•It is a versatile technology as it is used in the development of OTC medicines, Rx medicines and veterinary medicines.

•It is easily portable as it is a solid dosage form and less sensitive to enviornmental condition and does not require water to swallow the dosage form.

Conventional techniques for FDTs

Tablet moulding: In this method water soluble additives are used to form tablets. The ingradients used in the formulation are passed through the fine mesh, dry blended and wetted with hydroalcoholic solvent and then by using low compression forces compressed into tablets.

Freeze drying (Lyophilization): In this method water is removed by sublimation of the heat sensitive materials and biologicals. The porous tablets formed having improved absorption and bioavilability.

Spray drying: In this method highly porous fine powders are produced which when compressed into tablets show fast disintegration and enhanced dissolution.

Sublimation: In this method sublime salt is added to the components of tablets and by the process of sublimation the salt is removed and blend is compressed.

Addition of disintegrants: To improve the dissolution and disintegration, disintegrants are added in the FDTs.

Direct compression method: In this method the drug and the excipients are uniformly blended in a prescribed manner and directly compressed into tablet, withoutany pretreatment.The uniform blend of powders should have good flow properties, the disintegrants are added as excipients in direct compression method.

Patented technologies for FDTs

Zydias technology: Zydis is patented by R.P. Scherer. In this, drug is physically trapped in the matrix of saccharide and polymer. The Polymers used in this technology are hydrolyzed gelatin, hydrolyzed dextran, dextrin, alginates, polyvinyl alcohol, polyvinyl pyrrolidine, acacia and mixtures of these. Solution or dispersion of the ingradients is prepared and filled in the blister cavities; liquid nitrogen is used to freeze it. Then remove the fozen solvent or porous wafers are produced by sublimation. To pack zydis units’ peelable backing foil is used.

Durasolv technology: CIMA labs patented this technology. In this technique active drug is required in low amount. Drug, lubricant and fillers are used and the same equipments used in the conventional tablets are used in durasolv technique. The tablets formed are rigid due to higher compaction force and the tablets formed are packed in the blister packing.

Orasolv technology: First orodispersable tablet are prepared by CIMA labs. In this technique effervascent disintegrating agent is used. The equipments used in conventional tablets are used in orasolv technology. The taste of active drug is masked and tablet is formed by applying less compaction force. These soft tablets are packed in special packaging system.

Wowtab technology: This is the patented technology of Yamanauchi Pharmaceutical Company. The meaning of wow is “with out water”. In this technique the combination of high and low mouldable substances are used. The active ingradients are mixed with low mouldable saccharide and then granulated with high mouldable saccharide and compressed into tablets. These tablets are dissolved with in less than 15 sec. These tablets are packed into conventional bottles and blister packs.

Flash dose technology: This technology is patented by fuisz. The taste of bitter drugs is masked by sugar based matrix called floss. Nurofen meltlet, it is the mouth dissolving tablet of ibuprofen.

Flashtab technology: This technology is patented by prographarm lab. In this technique taste masked microgranules of active ingradients is prepared. These granules along with swelling agent, disintegrating agent and other excipient are compressed to form a multipartuculate tablet. These tablets are rapidly disintegrated.

NATURAL POLYMERS USED IN FAST DISSOLVING TABLETS

Aegle marmelos gum (AMG) 21: It is obtained from the fruits of aegle mermelos belonging to the family Rutaceae is indegenous to India. AMG is prepared by heat treatment technique. It increases the solubility of poorly soluble drugs. It increases glucose level and glycosylated haemoglobin in diabetic patients, decreases plasma insulin and liver glycogen in diabetic patient, decreases lipid peroxidation, stimulate macrophage functioning, it cause significant deviation in the GSH (glutathione) concentration in liver, kidney, stomach and intestine. Purified, bael-gum polysaccharide contains Dgalactose (71%), D-galacturonic acid (7%), Lrhamnose (6.5%), and L-arabinose (12.5%).

Upendra kulkarni et al formulate Aceclofenac fast dissolving tablets by using modified Aegle marmelos gum. Acelofenac is poory water soluble drug and have poor bioavilability after oral administration. Solubility of Acecofenac is increased with increase in concentration of AMG and Modified AMG. They concluded that Modified AMG could be used as potential carrier in the solubility and dissolution rate enhancement of poorly soluble drug. Increased dispersibility, surface area, wetability and solubilization effect of AMG and Modified AMG enhances the solubility of water insoluble drugs.

Lallemantia reylenne seeds20: It is also known as Tukhmalanga in India, it belongs to Lamiaceae family. It is an annual herb. It is cultivated in northern India. The seeds of Lallemantia reylenne seed are mucilagenous and have medicinal properties. It has extensive swelling properties. It is used to cure boil pain and bursting of boil. The seed due to the presence of high mucilage content quickly adsorb water when soaked and produce a sticky, turbid and tasteless liquid.

Karan malik et al formulate the orodispersable tablet of nimesulide by using Lallemantia reylenne seeds mucilage as a natural superdisintegrant. Increase in concentration of Lallemantia has appreciable effect on tablet hardness and friability which clearly indicated the binding potential of the seeds. Porosity of the tablet increases, the tablet is disintegrated faster and consistantly than the crosscarmellose sodium.

Locust bean gum22: It is also known as Carob ben gum. It is a galactomannan vegetable gum extracted from the seeds of carob tree (Ceretonia Siliqual) found in mediterranean region. Locust bean gum is used as gelling and thickning agent in food industry and used as bioadhesive and enhance the solubility. The gum is white to yellowish white odourless powder. It is insoluble in most organic solvent including ethanol. It is partially soluble in water at ambient temperature and soluble in hot water and need heating to above 850 for 10 min for complete solubility.

Karan malik et al formulate the nimesulide orodispersable tablets by using locus bean gum as natural superdisintegrant. The gum was evaluated for powder flow properties, swelling index and loss on drying. Excellent powder flow properties was observed, swelling index was found to be 20 it indicate the capability of locust bean gum used as superdisintegrant. Disintegration time of the tablet containing 10% locust bean gum was found to be 30 sec. The tablets disintegrated much faster and consistently when locust bean gum was used as superdisintegrant compared to cross carmellose sodium.

Ficus indica fruit mucilage23: The mucilage of ficus indica fruit is used as superdisintegrant which is obtained from the pulp of fruit ficus indica. Ficus indica is a large tree upto 3 meter and very fast growing with spready branches and arial roots. The fruits of ficus indica are of the size of cherry. It has nutritional as well as medicinal value. The dried and uncooked ficus indica fruit gives 230Kcal (963KJ) of energy per 100gm (3.5 oz)5. It is used in relieving fever, pain, inflammation, wound healing, blood problems and urinary problems.

Hindustan Abdul Ahad et al extracted the mucilage of ficus indica fruit and evalute its physical chemical and flow properties like the extracted mucilage is yellow in colour and have characterstic odour, it is soluble in water and produce a hage viscous solution and concluded that the mucilage has good physiochemical and good flow properties. The mucilage is used as binder in the tablet formulation.

Mangifera indica gum24(MIG): Common name of mangifera indica is mango belongig to Anacardiaceae family.It is non toxic and used as disintegrant, binder, suspending agent, emulsifying agent in different formulations. The gum is white to off white in colour to cream colour powder, the powder was soluble in water and practically insoluble in acetone chloroform, ether, methanol and ethanol It is easily available and gum is deviod of toxicity and each and every part of the tree has pharmacological activity like diuretic, astringent, diabetes, asthma, diahorrea, urethritis, and scabies.

Ravi kumar nayak et al formulate the fast dissolving tablets of Metforin HCl, it is utilised in low concentration and the tablet formulated have good appearance and better release property. The wetting time of the fomulated tablet was found to be 38-88 s. It is concluded that the disintegrant property of MIG powder is better than crosspovidone. It is used 6% w/w in the tablet formulation.

Lepedium Sativum25: It is also called Asaliyo and belonging to the family Cruciferae. Mucilage is extracted from the seeds of lepedium sativum which is used as binder, disintegrant and gelling agent. It is used in India as herbal medicine. The mucilage is brownish white powder which have characterstic odour and decomposes above 2000C. Various physiochemical properties are evaluated as swelling index is found to be 18, angle of Repose is 320C, bulk density is 0.58g/cc and tapped density is found to be 0.69g/cc.

Kaplesh K Mehta et al Formulate the fast dissolving tablets of Nimesulide using Lepedium Sativum used as natural polymer as disintegrating agent. At mucilage concentration 10% and also mannitol concentration 10% the higher dissolution of tablet is observed. Disintegration time is 17sec and dissolution time is 5-27 sec. Lepedium sativum mucilage give fast drug release rate as compared to Ac-di-sol and SSG.

Hibiscus Rosa sinensis mucilage and treated agar26: It is also called shoe flower plant, China rose, Chinese hibiscus belonging to family Malvaceae. Mucilages are used as thickeners, suspending agent, water retention agent, disintegrants. The plant is easily available and its leaves contain mucilage and in mucilage L-rhamnose, D-galactose, D-galactouronic acid and D-glucuronic acid is present. Treated agar is prepared by treating it with water for one day.

Halakatti prabhu k et al develop the mouth dissolving tablet of famotidine by adding Hibiscus rora sinensis mucilage and treated agar as super disintegrating agent.With the increase in polymer concentration there is decrease in disintegration time and decrease in dissolution of the drug. 90% of the drug is released from all the formulation with in 10min. It is concluded that Hibiscus Rosa sinensis mucilage and teated agar shows good disintegration property.

Dehydrated banana powder (DBP) 27: Banana is also called Plantain. DBP is prepared from the variety of banana called Ethan and nenthran (nenthra vazha) belonging to the family Musaceae. It contains vitamin A so used in the treatment of gastric ulcer and diahorrea. It also contains vitamin B6, which help in reducing the stress and anxiety. It is a very good source of energy due to high carbohydrate content and it contain pottasium which is responsible for better brain functioning.

N Arun kumar et al Orodispersable tablet of ondansetron HCl, propanolol and Gabapectin is prepared by using DBP as superdisintegrant. It acts as binder, diluent and superdisintegrant. It acts as binder, diluent and superdisintegrant. It increases the release rate of drug from the tablet.

Chitosan and Gum Arabic28: Chitosan is cationic polysaccharide derived from the Ndeacetylation of Chitin. Gum Arabic is a natural polysaccharide derived from exudates of Acacia Senegal and Acacia Senegal trees.

Rishabha Malviya et al concluded that by the presence of chitosan and gum arabic co-aservates the release rate of drug from the tablet formulation increases and used in the treatment of chronic disorder at the initial stage of chronic attack.

Plantago ovata29: Plantago ovata mucilage is used as natural superdisintegrant. The mucilage also has various properties like binding, disintegrating and sustaining property. The dried seeds of Isapghula husk of a plant called as plantago ovata. The swelling index of the tablets is around 89+ 2.2%v/v. FDTs are rapidly disintegrated due to the presence of mucilage which create hydrodyanamic pressure. The mucilage is clear, colourless gel; it is obtained from the seed coat of psyllium. Milled seed mucilage is white fibrous material which is hydrophilic in nature.

N G Raghavendra Rao et al prepare the fast dissolving tablets of Cabamazepine by adding superdisintegrant plantago ovata seed powder and mucilage. Carbamazepine is poorly soluble drug its solubility, bioavailability and effectiveness increases by adding plantago ovata seed powder and mucilage as superdisintegrating agent.

CONCLUSION

It was concluded from the above study that Natural polymers have better effects on fast dissolving tablets than Synthetic Polymers. Natural Polymers increased the drug release rate from the tablet, decrease the dissolution and disintegration time, used as binder superdisintegrant, diluent. Natural polymers are preferred over synthetic polymers as they are nontoxic, easily available at low cost used in low concentration and as they are naturally extracted provide nutritional supplement.

Conflict of Interest

NIL

Source of Support

NONE

Tables at a glance

Table 1

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