AN OVERVIEW ON FAST DISSOLVING DRUG DELIVERY SYSTEM

Nandy et al. / AJPSR volume 1 issue 2, July 2011

1 Nandy et al. / AJPSR Volume 1 Issue 2, July 2011

Available online at www.ordonearresearchlibrary.com ISSN 2249 - 4898

ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH

AN OVERVIEW ON FAST DISSOLVING DRUG DELIVERY SYSTEM

Bankim Chandra Nandy 1*, Bhaskar Mazumder 2, Kadambari Pathak1, Nidhi Saxena 1, Swati Jain 1, Stuti Sharma 1, Rughani Amishaben1, Arti Shrivastava1, Priya Saxena1

1 Department of Pharmaceutical Sciences, Jayoti Vidyapeeth Women’s University, Jaipur, Rajasthan, India

2 Department of Pharmaceutical Sciences, Dibrugarh University, Assam, India Received: 21 May 2011; Revised: 14 June 2011; Accepted: 20 July 2011; Available online: 5 Aug. 2011

INTRODUCTION

Recent developments in technology have presented viable dosage alternatives for patients who may have

difficulty swallowing tablets or liquids. Traditional tablets and capsules administered with an 8-oz. glass of

water may be inconvenient or impractical for some patients. However, some patients, particularly pediatric and

geriatric patients, have difficulty swallowing or chewing solid dosage forms. Many pediatric and geriatric

patients are unwilling to take these solid preparations due to a fear of choking. In order to assist these patients,

several fast-dissolving drug delivery systems have been developed [1]. For example, a very elderly patient may

not be able to swallow a daily dose of antidepressant. An eight-year-old with allergies could use a more

Review Article

ABSTRACT Swallowing a tablet is a major difficulty encountered in case of geriatric and pediatric patient which leads to poor patient compliance due to unpalatable taste of drug. To troubleshoot these problems a new dosage form known as fast-dissolving tablet, has been developed which rapidly disintegrate and dissolve in saliva. Now a number of fast-dissolving formulations are in market like Claritin Reditab (Manufacturer R.P.Scherr,Inc.), Risperdal M-Tab (Manufacturer Janseen pharmaceutics.), Tempra Quicklets (Manufacturer Cima Labs,inc) and the technology is still improving. The conventional tablet seems to be most popular because of its ease of transportability and comparatively low manufacturing cost but poor patient compliance in case of pediatrics and geriatrics patients who experienced difficulties in swallowing, in response to this mouth dissolving drugs delivery system (MDDs) were developed as an alternative to tablet, cap & syrups. A variety of MDDs like mouth dissolving tablets and mouth dissolving film (MDFs) were commercialized. MDFs evolved over the past few years from by the confection and oral care market in the form of breath strips & became a novel & widely accepted form by consumers. The aim of the present review was to study the feasibility of fast dissolving drug delivery systems. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade and the field has become a rapidly growing area in the pharmaceutical industry because of such tablets readily dissolve or disintegrate in the saliva generally less than 60 seconds. Keywords: Fast dissolving drug delivery system (FDDS), Superdisintegrators, Mouth dissolving tablets, Mouth dissolving film (MDFs)

http://www.ordonearresearchlibrary.com/



convenient dosage form than antihistamine syrup. A schizophrenic patient in the institutional setting can hide a

conventional tablet under his or her tongue to avoid their daily dose of an atypical antipsychotic. A middle-aged

woman undergoing radiation therapy for breast cancer may be too nauseous to swallow her H2-blocker. Fast-

dissolving/disintegrating tablets (FDDTs) are a perfect fit for all of these patients. The target populations for

these new fast-dissolving/disintegrating dosage forms have generally been pediatric, geriatric, and bedridden or

developmentally disabled patients. Patients with persistent nausea, who are traveling, or who have little or no

access to water are also good candidates for FDDTs [2]. FDDTs disintegrate and/or dissolve rapidly in the

saliva without the need for water. Some tablets are designed to dissolve in saliva remarkably fast, within a few

seconds, and are true fast-dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in

the oral cavity, and are more appropriately termed fast-disintegrating tablets, as they may take up to a minute to

completely disintegrate. When put on tongue, this tablet disintegrates instantaneously, releasing the drug, which

dissolves or disperses in the saliva. Some drugs are absorbed from the mouth, pharynx and esophagus as the

saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those

observed from conventional tablet dosage form [3, 4]. The major advantage of the FDDT formulation is that it

combines the advantages of both liquid and conventional tablet formulations, while also offering advantages

over both traditional dosage forms. It provides the convenience of a tablet formulation, while also allowing the

ease of swallowing provided by a liquid formulation. FDDTs allow the luxury of much more accurate dosing

than the primary alternative, oral liquids [4].

The aim of the present review was to study the feasibility of fast dissolving drug delivery and this review briefly

describes the background, advantages, salient feature, patented technologies and various excipients used to fast

dissolving drug delivery system and summarizes the studies conducted recently using this technique in order to

achieve higher systemic absorption of the drugs having poorly water soluble in nature.

Background

Approximately one-third of the population, primarily the geriatric and pediatric populations, has swallowing

difficulties, resulting in poor compliance with oral tablet drug therapy which leads to reduced overall therapy

effectiveness. A new tablet dosage format, the fast dissolving tablet has been developed which offers the

combined advantages of ease of dosing and convenience of dosing in the absence of water or fluid. These

tablets are designed to dissolve or disintegrate rapidly in the saliva generally less than 60 seconds. Due to the

constraints of the current FDDT technologies as highlighted above, there is an unmet need for improved

manufacturing processes for fast dissolving tablets that are mechanically strong, allowing ease of handling and

packaging and with production costs similar to that of conventional tablets [5].

Technology Description/Development Stage



Formulation advances using a conventional tabletting process have led to the development of mechanically

robust tablets which readily dissolve/disintegrate within <50 seconds and can be formulated in a range of sizes

from 10 -15mm. The tablets produced are stable, and can withstand shipment in conventional tablet containers

without loss of integrity. Pre-clinical canine studies with a range of formulations have demonstrated palatability

and ease of administration [5].

Salient Features of Fast Dissolving Drug Delivery System [6, 7]

Ease of administration to patients who refuse to swallow a tablet, such as pediatric and geriatric patients and,

psychiatric patients.

Convenience of administration and accurate dosing as compared to liquids.

No need of water to swallow the dosage from, which is highly convenient feature for patients who are

traveling and do not have immediate access to water.

Good mouth feels properly of MDDS helps to change the basic view of medication as "bitter pill",

particularly for pediatric patients.

Rapid dissolution of drug and absorption which may produce rapid, onset of action.

Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the

stomach; in such cases bioavailability of drugs is increased.

Ability to provide advantages of liquid medication in the form of solid preparation.

Pregastric absorption can result in improved bioavailability and as a result of reduced dosage, improved

clinical performance through a reduction of unwanted effects.

An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs, due to rapid

disintegration and dissolution of these tablets.

Stability for longer duration of time, since the drug remains in solid dosage form till it is consumed. So, it

combines advantage of solid dosage form in terms of stability and liquid dosage form in terms of

bioavailability.

Demerits

Formulations are hygroscopic, fragile and effervescence in nature [8].

Needs

The need for non-invasive delivery systems continues due to patients' poor acceptance and compliance with

existing delivery regimes, limited market size for drug companies and drug uses, coupled with high cost of

disease management. The current needs of the industry are improved solubility/stability, biological half-life and

bioavailability enhancement of poorly absorbed drugs. Key issues facing the biopharma industry are to improve

safety (decreasing gastrointestinal side effects), improve efficacy for organ targeting, and improved compliance



via sustained release or easy to swallow dosage forms. Developing new drug delivery technologies and utilizing

them in product development is critical for pharmaceutical companies to survive. This applies to all

pharmaceutical companies, regardless of their size. In his book, Jurgen Drews has emphasized that the

pharmaceutical industry must accomplish more than it has to date with more modest financial resources [9].

Characteristics of Fast Dissolving Delivery Systems

Ease of administration

Fast Dissolving Delivery Systems are easy to administer and handle hence, leads to better patient compliance.

Usually, elderly people experience difficulty in swallowing the conventional dosage forms (tablets, capsules,

solutions and suspensions) because of tremors of extremities and dysphasia. Fast Dissolving Delivery Systems

may offer a solution for these problems [10].

Taste of the medicament

Mouth dissolving delivery systems usually contain the medicament in taste masked form. Taste-masking is of

critical importance in the formulation of an acceptable FDDT. Traditional tablet formulations generally do not

address the issue of taste masking, because it is assumed that the dosage form will not dissolve until passing the

oral cavity. Many oral suspensions, syrups, and chewable tablets simply contain flavors, sugars and other

sweeteners to overwhelm or complement the bitter taste of the drug [11]. Current methods of taste masking in

fast dissolving/disintegrating tablets include sweeteners and flavors; however, these are not a sufficient means

for taste-masking many bitter drugs.

Hygroscopicity

Several fast dissolving dosage forms are hygroscopic and cannot maintain physical integrity under normal

condition from humidity which calls for specialized product packaging [5].

Friability

In order to allow fast dissolving tablets to dissolve in the mouth, they aremade of either very porous and soft-

moulded matrices or compressed into tablets with very low compression force, which makes the tablets friable

and/or brittle which are difficult to handle, often requiring specialized peel-off blister packaging[10].

http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijpharm/vol4n2/drug.xml



Mouth feel

Mouth feel is critical, and patients should receive a product that feels pleasant. Any large particles from the

disintegrating tablet that are insoluble or slowly soluble in saliva would lead to an unpleasant gritty feeling. This

can be overcome by keeping the majority of the particles below the detectable size limit. In some cases, certain

flavors can imbibe an improved mouth feel perception, resulting in a product that is perceived as being less

gritty, even if the only change is the flavor. Effervescence can be added to aid disintegration and improve mouth

feel by reducing the “dryness” of a product [12].

Approaches for Fast Dissolving Tablets

The fast-dissolving property of the tablet is attributable to a quick ingress of water into the tablet matrix

resulting in its rapid disintegration.

Conventional Technologies for Fast Dissolving Tablets

Freeze drying or Lyophilization

The tablets prepared by freeze-drying or lyophilization are very porous in nature and disintegrate or dissolve

rapidly when come in contact with saliva. In this process, water is sublimated from the product after freezing.

First of all, the material is frozen to bring it below its eutectic point. Then primary drying is carried out to

reduce the moisture to around 4% w/w of dry product. Finally, secondary drying is done to reduce the bound

moisture to the required volume. However the use of freeze-drying is limited due to high cost of equipment and

processing. Other major disadvantages of the final dosage forms include lack of physical resistance in standard

blister packs [13].

Moulding

Tablets prepared by this method are solid dispersions. Physical form of drug in the tablets depends on whether

and to what extent it dissolves in the wetted mass. The drug can exist as discrete particles or micro particles in

the matrix. It can dissolve totally to form a solid solution or dissolve partially in the molten carrier and

remaining, if any, stays undissolved and dispersed in the matrix. Disintegration time, drug dissolution rate and

mouth feel will depend on the type of dispersion [13].

Different moulding techniques can be used to prepare mouth-dissolving tablets:

Compression moulding

The powder mixture previously wetted with a solvent like ethanol/water is compressed into mould plates to

form a wetted mass.



Heat moulding

A molten matrix in which drug is dissolved or dispersed can be directly moulded into Orodispersable Tablets.

No vacuum lyophilization

This process involves evaporation of solvent from a drug solution or suspension at a standard pressure.Moulded

tablets possess porous structure, which facilitates rapid disintegration and easy dissolution. Moulded tablets

offer improved taste due to water-soluble sugars present in dispersion matrix. But moulded tablets lack good

mechanical strength and can undergo breakage or erosion during handling and opening of blister

packs.However, adding sucrose, acacia or polyvinyl pyrrolidone can increase mechanical strength [13].

Spray drying

Spray drying can produce highly porous and fine powders that dissolve rapidly. The formulations are

incorporated by hydrolyzed and non hydrolyzed gelatins as supporting agents, mannitol as bulking agent,

sodium starch glycolate or crosscarmellose sodium as disintegrating and an acidic material (e.g. citric acid) and

/ or alkali material (e.g. I sodium bicarbonate) to enhance disintegration and dissolution. Tablet compressed

from the spray dried powder disintegrated within 20 seconds when immersed in an aqueous medium [6, 13].

Sublimation

The slow dissolution of the compressed tablet containing even highly water-soluble ingredients is due to the low

porosity of the tablets. Inert solid ingredients that volatilize readily (e.g. urea, ammonium carbonate, ammonium

bicarbonate, hexamethelenetetramine, camphor etc.) were added to the other tablet ingredients and the mixture

is compressed into tablets. The volatile materials were then removed via sublimation ( Fig. 1), which generates

porous structures. Additionally, several solvents (e.g. cyclohexane, benzene) can be also used as pore forming

agents [6].



Figure 1 Various steps involve in sublimation

Direct compression

Direct compression represents the simplest and most cost effective tablet manufacturingtechnique. This

technique can now be applied to preparation of ODT because of the availability of improved excipients

especially superdisintegrants and sugar based excipients [7].

Superdisintegrants

In many orally disintegrating tablet technologies based on direct compression, the addition of superdisintegrants

principally affects the rate of disintegration and hence the dissolution. The presence of other formulation

ingredients such as water-soluble excipients and effervescent agents further hastens the process of disintegration

[7].

Sugar Based Excipients

This is another approach to manufacture ODT by direct compression. The use of sugar based excipients

especially bulking agents like dextrose, fructose, isomalt, lactilol, maltilol, maltose, mannitol, sorbitol, starch

hydrolysate, polydextrose and xylitol, which display high aqueous solubility and sweetness, and hence impart

taste masking property and a pleasing mouthfeel [7].

Taste masking

Taste masking is an essential requirement for fast dissolving tablets for commercial success. Taste masking of

the active ingredients can be achieved by various techniques. Drugs with unacceptable bitter taste can be

microencapsulated into pH sensitive acrylic polymers. Cefuroxime axetil is microencapsulated in various types

of acrylic polymers (e.g., Eudragit E, Eudragit L-55 and Eudragit RL) by solvent evaporation and solvent



extraction techniques. These polymer micro spheres showed efficient taste masking and complete dissolution in

a short period. Fine granules of drug and disintegrant (e.g. low substituted hydroxypropyl cellulose) when

coated with a water insoluble polymer (e.g. ethyl cellulose) masked the bitter taste of sparfloxacin. The addition

of low substituted hydroxypropyl cellulose as disintegrant to the drug in cores resulted in increased dissolution

rate and bioavailability of sparfloxacin compared to its conventional tablets [10, 13].

Mass extrusion

This technology involves softening of the active blend using the solvent mixture of water-soluble polyethylene

glycol and methanol and subsequent expulsion of softened mass through the extruder or syringe to get a

cylinder of the product into even segments using heated blade to form tablets [14].

Cotton Candy Process

This process is so named as it utilizes a unique spinning mechanism to produce floss-like crystalline structure,

which mimic cotton candy. Cotton candy process involves formation of matrix of polysaccharides or

saccharides by simultaneous action of flash melting and spinning. The matrix formed is partially recrystallized

to have improved flow properties and compressibility. This candy floss matrix is then milled and blended with

active ingredients and excipients and subsequently compressed to ODT. This process can accommodate larger

drug doses and offers improved mechanical strength. However, high-process temperature limits the use of this

process [14].

Patented Technologies for Fast Dissolving Drug Delivery Systems

Currently, four fast-dissolving/disintegrating technologies have reached the U.S. market [15, 16, 17]:

(i) Zydis (R.P. Scherer, Inc.), (ii) WOWTAB (Yamanouchi Pharma Technologies,Inc.),

(iii) OraSolv (Cima Labs, Inc.), (iv) DuraSolv (Cima Labs, Inc.).

Others Patented Technologies of FDDS [15, 16, 17]:

(i) FlashDose (Fuisz Technologies, Ltd.) (ii) Flashtab (Prographarm Group), (iii) OraQuick (KV Pharmaceutical

Co., Inc.) (iv) Quick –Dis Technology (Lavipharm Laboratories Inc.) (v) Ziplets/Advatab, (Passano con

Barnago, Italy) (vi) Lyoc technology (PHARMALYCO) (vii) Pharmaburst technology (SPI Pharma, New

Castle) (viii) Frosta technology (Akina) (ix) Nanocrystal Technology (Elan, King of Prussia) (x) Quick solv

(Janssen Pharmaceuticals).

Currently, four fast-dissolving/disintegrating technologies have reached the U.S. market

Zydis Technology



Scherer has patented the Zydis technology. Zydis, the best known of the fast-dissolving/disintegrating tablet

preparations, was the first marketed new technology tablet. The tablet dissolves in the mouth within seconds

after placement on the tongue.

A Zydis tablet is produced by lyophilizing or freeze-drying the drug in a matrix usually consisting of gelatin.

The product is very lightweight and fragile, and must be dispensed in a special blister pack. Patients should be

advised not to push the tablets through the foil film, but instead peel the film back to release the tablet. The

Zydis product is made to dissolve on the tongue in 2 to 3 seconds. In addition, it utilizes microencapsulation

with specialized polymers or complexation with ion exchange resins to mask the bitter tasting drug. The

combination of lyophilization and taste masking creates a product that is both pleasing to the eye and also to the

senses of taste and touch [3].

Wowtab Technology

The Wowtab fast-dissolving/disintegrating tablet formulation has been on the Japanese market for a number of

years. Wowtab technology is patented by Yamanouchi Pharmaceutical Co. The WOW in Wowtab signifies the

tablet is to be given “With out Water”. It has just recently been introduced into the U.S. The Wowtab

technology utilizes sugar and sugar-like (e.g., mannitol) excipients. This process uses a combination of low

mouldability saccharides (rapid dissolution) and high mouldability saccharide(good binding property).The two

different types of saccharides are combined to obtain a tablet formulation with adequate hardness and fast

dissolution rate.Due to its significant hardness, the Wowtab formulation is a bit more stable to the environment

than the Zydis or OraSolv [16, 17].

Orasolv Technology

OraSolv was Cima's first fast-dissolving/disintegrating dosage form. The OraSolv technology, unlike Zydis,

disperses in the saliva with the aid of almost imperceptible effervescence. The OraSolv technology is best

described as a fast-disintegrating tablet; the tablet matrix dissolves in less than one minute, leaving coated drug

powder. The taste masking associated with the OraSolv formulation is two-fold. The unpleasant flavor of a drug

is not merely counteracted by sweeteners or flavors; both coating the drug powder and effervescence are means

of taste masking in OraSolv. This technology is frequently used to develop over-the-counter formulations. The

major disadvantage of the OraSolv formulations is its mechanical strength because the Orasolve tablets are only

lightly compressed. An advantage that goes along with the low degree of compaction of OraSolv is that the

particle coating used for taste masking is not compromised by fracture during processing [15].

Durasolv Technology

DuraSolv is Cima's second-generation fast-dissolving/disintegrating tablet formulation. Produced in a fashion

similar to OraSolv, DuraSolv has much higher mechanical strength than its predecessor due to the use of higher

compaction pressures during tableting.DuraSolv is so durable that it can be packaged in either traditional blister



packaging or vials. DuraSolv tablets are prepared by using conventional tabletting equipment and have good

rigidity(friability less than that 2%). The DuraSolv product is thus produced in a faster and more cost-effective

manner. One disadvantage of DuraSolv is that the technology is not compatible with larger doses of active

ingredients, because the formulation is subjected to such high pressures on compaction. Unlike OraSolv, the

structural integrity of any taste masking may be compromised with high drug doses.The drug powder coating in

DuraSolv may become fractured during compaction, exposing the bitter-tasting drug to a patient's taste buds.

Therefore, the DuraSolv technology is best suited for formulations including relatively small doses of active

compound [16].

Others Patented Technologies of FDDS

Flash Dose Technology

Fuisz Technologies has three oral drug delivery systems that are related to fast dissolution. The first two

generations of quick-dissolving tablets, Soft Chew and EZ Chew, require some chewing. However, these paved

the way for Fuisz's most recent development, Flash Dose. The Flash Dose technology utilizes a unique spinning

mechanism to produce a floss-like crystalline structure, much like cotton candy. This crystalline sugar can then

incorporate the active drug and be compressed into a tablet. This procedure has been patented by Fuisz and is

known as Shearform. The final product has a very high surface area for dissolution. It disperses and dissolves

quickly once placed onto the tongue. Interestingly, by changing the temperature and other conditions during

production, the characteristics of the product can be altered greatly [2].

Flashtab Technology

Prographarmlaboratories has patented the Flashtab technology. This technology involves the preparation of

rapidly disintegrating tablet which consists of an active ingredient in the form of microcrystals. Drug micro-

granules may be prepared by using the conventional techniques like coacervation, extrusion-spheronization,

simple pan coating methods and microencapsulation. The microcrystals of micro-granules of the active

ingredient are added to the granulated mixture of excipients prepared by wet or dry granulation, and compressed

into tablets. All the processing utilized the conventional tabletting technology, and the tablets produced are

reported to have good mechanical strength and disintegration time less than one minute [17].

Oraquick Technology

The OraQuick fast-dissolving/disintegrating tablet formulation utilizes a patented taste masking technology. KV

Pharmaceutical claims its microsphere technology, known as MicroMask, has superior mouth feel over taste-

masking alternatives. The taste masking process does not utilize solvents of any kind, and therefore leads to

faster and more efficient production. Also, lower heat of production than alternative fast-

dissolving/disintegrating technologies makes OraQuick appropriate for heat-sensitive drugs. KV Pharmaceutical



also claims that the matrix that surrounds and protects the drug powder in microencapsulated particles is more

pliable, meaning tablets can be compressed to achieve significant mechanical strength without disrupting taste

masking [14].

Quick –Dis Technology

Lavipharm Laboratories Inc. (Lavipharm) has invented an ideal intraoral fast-dissolving drug delivery system,

which satisfies the unmet needs of the market. The novel intraoral drug delivery system, trademarked Quick-

Dis™, is Lavipharm’s proprietary patented technology and is a thin, flexible, and quick-dissolving film. The

film is placed on the top or the floor of the tongue. It is retained at the site of application and rapidly releases the

active agent for local and/or systemic absorption. The Quick-Dis™ drug delivery system can be provided in

various packaging configurations, ranging from unit-dose pouches to multiple-dose blister packages [17].

Ziplets/Advatab

This technology is patented by passano con Barnago, Italy. It utilizes water-insoluble ingredient combined with

one or more effective disintegrants to produce ODT with improved mechanical strength and optimal

disintegration time at low compression force. This technology handles high drug loading and coated drug

particles and does not require special packaging, so they can be packed in push through blisters or bottles [18].

Lyoc

Lyoc technology is patented by PHARMALYCO. Oil in water emulsion is prepared and placed directly into

blister cavities followed by freeze-drying. Nonhomogeneity during freeze-drying is avoided by incorporating

inert filler to increase the viscosity finally the sedimentation. High proportion of filler reduces porosity of

tablets due to which disintegration is lowered [18].

Pharmaburst technology

SPI Pharma, New Castle, patents this technology. It utilizes the co-processed excipients to develop ODT, which

dissolves within 30-40 s. this technology involves dry blending of drug, flavor, and lubricant followed by

compression into tablets. Tablets obtained have sufficient strength so they can be packed in blister and bottles

[18].

Frosta technology

Akina patents this technology. It utilizes the concept of formulating plastic granules and compressing them at

low pressure to produce strong tablets with high porosity. Plastic granules composed of porous and plastic



material, water penetration enhancer, and binder. The tablets obtained have excellent hardness and rapid

disintegration time ranging from 15 to 30 sec depending on size of tablet [14].

Nanocrystal Technology

This is patented by Elan, King of Prussia. Nanocrystal technology includes lyophilization of colloidal

dispersions of drug substance and water-soluble ingredients filled in to blister pockets. This method avoids

manufacturing process such as granulation, blending, and tableting, which is more advantageous for highly

potent and hazardous [18].

Quick solv

This technology is patented by Janssen Pharmaceuticals. It utilizes two solvents in formulation a matrix, which

disintegrates instantly. Methodology includes dissolving matrix components in water using an excess of alcohol

(solvent extraction). Thus the product formed has uniform porosity and adequate strength for handling [18, 19].



Table 1: Comparison of Fast Dissolving Techniques [17]

ZYDIS (R.P. SCHERER, INC.)

Novelty Handling/Storage Drug Release/Bioavailability

First to market Do not push tablet through foil Dissolves in 2 to 10 seconds

Freeze Dried

Do not use dosage form from

damaged package

May allow for pre-gastric absorption

leading to enhanced bioavailability

Sensitive to degradation at humidities>65%

ORASOLV (CIMA LABS, INC.)


Unique taste masking Packaged in patented foil packs

Disintegrates in 5 to 45 seconds depending

upon the size of the tablet

Lightly compressed No significant change in drug bioavailability

DURASOLV (CIMA LABS, INC.)


Similar to Orasolv, but with

better mechanical strength

Packaged in foil or bottles

Disintegrates in 5 to 45 seconds depending

upon the size of the tablet

If packaged in bottles, avoid

exposure to moisture or humidity

No significant change in drug bioavailability

WOWTAB (YAMANOUCHI PHARMA TECHNOLOGIES, INC.)


Compressed dosage form Package in bottles

Disintegrates in 5 to 45 seconds depending upon

the size of the tablet

Proprietary taste masking

Avoid exposure to

moisture or humidity

No significant change in drug bioavailability

FLASHDOSE (Fuisz Technologies, Ltd.)


Unique spinning mechanism to

produce a floss-like crystalline

structure

Avoid exposure to


Dissolves within 1 minute

Require specialized packaging Enhanced bioavailability

FLASHTAB (Prographarm Group)


Compressed dosage form

containing Drug as microcrystals

Avoid exposure to


Dissolves within 1 minute



Table 2: Orally Disintegrating Tablet Products Available in Indian Market [10,14,18]

Brand Name Active Ingredient Company

Domray MD Domperidone Ray Remedies

Velrid MD Domperidone Shreyam Health Care

Vomidon MD Domperidone Olcare Lab

Zotacet MD Cetrizine HCL ZotaPharma

OlanexInstab Olanzepine Ranbaxy

Manza RDT Olanzepine Mano Pharma (Orchid)

Romilast Montelukast Ranbaxy

Torrox MT Rofecoxib Torrent

Ziflam Rofecoxib Kopran

Doloroff Rofecoxib Indoco

Rofaday MT Rofecoxib Lupin

Dolib MD Rofecoxib Panacea

Orthoref MD Rofecoxib Biochem

Rbcox-25 MD Rofecoxib ShalmanPharma

Roffec MD Rofecoxib Excare Lab

Rofftab MD Rofecoxib Olcare Lab

Zofex-25 MD Rofecoxib ZotaPharma

Valus Valdecoxib Glenmark

Nancy MD Nimesulide Zenon Health Care

Nexus MD Nimesulide Lexus

Nimex MD Nimesulide Mexon Health Care

Nimez- MD Nimesulide ZotaPharma

Nisure-MD Nimesulide SuzenPharma

Nimulid-MD Nimesulide Panacea

Olnim- MD Nimesulide Olcare Lab

Sulbid- Md Nimesulide Alpic remedies

Topmide Nimesulide Antigen Health Care

Nimpain MD Nimesulide Prompt Cure Pharma

Mosid MT Mosapride Torrent



Excipients used to prepare FDDT’s these are following type [17, 18]

Super disintegrants: Crosspovidone, Microcrystalline cellulose, sodium starch glycollate, sodium carboxy

methyl cellulose, pregelatinzed starch, calcium carboxy methyl cellulose, and modified corn starch. Sodium

starch glycollate has good flowability than crosscarmellose sodium. Cross povidone is fibrous nature and highly

compactable.

Flavours: Peppermint flavour, cooling flavor, flavor oils and flavoring aromatic oil, peppermint oil, clove oil,

bay oil, anise oil, eucalyptos oil thyme oil, oil of bitter almonds. Flavoring agnets include, vanilla, citus oils,

fruit essences

Sweetners: Aspartame, Sugars derivatives

Fillers: Directly compressible spray dried Mannitol, Sorbitol, xylitol, calcium carbonate, magnesium carbonate,

calcium phosphate, calcium sulfate, pregelatinized starch, magnesium trisilicate, aluminium hydroxide.

Surface active agents: sodiumdoecylsulfate, sodiumlaurylsulfate, polyoxyethylene sorbitan fatty acid esters

(Tweens), sorbitan fatty acid esters (Spans), polyoxyethylene stearates.

Binder: Polyvinylpyrrolidone(PVP), Polyvinylalcohl(PVA), Hydroxypropyl methylcellulose(HPMC)

Colour: Sunset yellow, Amaranth etc.

Lubricants: Stearic acid, Magnesium stearate, Zinc state, calcium state, talc, polyethylene glycol, liquid

paraffin, magnesium laury sulfate, colloidal silicon dioxide.

Table 3: Drug Suitable for Fast Dissolving Drug Delivery System [20]

Category Drug

NSAIDS Ketoprofen, Piroxicam, Paracetomol, Rofecoxib, Nimesulide

Ibuprofen, Tepoxaline (Cainine NSAID)

Anti-ulcer Famotidine, Lansoprazole

Anti-histaminic Loratadine, Diphenhydramine, Meclizine

Hypnotics and sedatives Zolpidem, Clonazepam, Atenolol

Antipsychotics Olanzepine, Risperidone, Pirenzepine



Antiparkinsonism Selegiline

Antiemetic Ramosetoron HCl, Ondansetron, Baclofen

Antimigrane Sumatriptan, Rizatriptan benzoate, Zolmitriptan

Antidepressant Mitraxepine, Fluoxetine

Miscellaneous Baclofen, Hydrochlorthiazide, Tramodol HCL

Propyphenazone, Spiranolactone, Phloroglucinol, Sildenafil

Mechanism of Superdisintegrants

Swelling

Perhaps the most widely accepted mechanism of action for tablet disintegration is swelling. Tablets with high

porosity show poor disintegration due to lack of adequate swelling force. Sufficient swelling force is exerted in

the tablet with low porosity. It is worthwhile to note that if the packing fraction is very high, fluid is unable to

penetrate in the tablet and disintegration is again slows down.

Porosity and capillary action (Wicking)

Disintegration by capillary action is always the first step. When we put the tablet into suitable aqueous medium,

the medium penetrates into the tablet and replaces the air adsorbed on the particles, which weakens the

intermolecular bond and breaks the tablet in to fine particles. Water uptake by tablet depends upon

hydrophilicity of the and on tableting conditions. For these types of disintegrants maintenance of porous

structure and low interfacial tension towards aqueous fluid is necessary which helps in disintegration by

creating a hydrophilic network around the drug particle [19].

Due to disintegrating particle/particle repulsive forces

Another mechanism of disintegration attempts to explain the swelling of tablet made with ‘nonswellable’

disintegrants. Guyot-Hermann has proposed a particle repulsion theory based on the observation that

nonswelling particle also cause disintegration of tablets. The electric repulsive forces between particles are the

mechanism of disintegration and water is required for it. Researchers found that repulsion is secondary to

wicking [19].

Due to deformation

During tablet compression, disintegrant particles get deformed and these deformed particles get into their

normal structure when they come in contact with aqueous media or water. Occasionally, the swelling capacity

of starch was improved when granules were extensively deformed during compression. This increase in size of



the deformed particles produces a breakup of the tablet. This may be a mechanism of starch and has only

recently begun to be studied.

Solid Dispersion

Solid dispersion is comparable to liquid solutions, consisting of just one phase irrespective of the number of

components. Solid dispersion of poorly water soluble drug dissolved in a carrier with relatively good aqueous

solubility of particular interest as a means of improving oral bioavailability. In the case of solid dispersion, the

drug's particle size has been reduced to its absolute minimum viz. The molecular dimensions and the dissolution

rate are determined by the dissolution rate of the carrier [21].

Classification of solid dispersion [21]

Solid dispersions can be classified according to two methods. First, they can be classified according to their

miscibility (continuous versus discontinuous solid solutions) or second, according to the way in which the

solvate molecules are distributed in the solvendum (substitutional, interstitialor amorphous).

Figure 2: Steps Involved in Mechanism of Wicking and Swelling



Figure 3: Steps Involved in Mechanism of Deformation and Repulsion

Table 4: List of Superdisintegrants [7]

Superdisintegrants Example Mechanism Of

action

Special comment

Crosscarmellose®

Ac-Di-Sol®

Nymce ZSX®

PrimelloseRSolutab®

Vivasol® L-HPC

Cross-linked

Cellulose

-Swells 4-8 folds in

< 10 seconds.

-Swelling and wicking

both.

-Swells in two dimensions.

-Direct compression or

granulation

-Starch free

CrosspovidoneCrosspovidon

M®

Kollidon®

Polyplasdone®

Cross-linked

PVP

-Swells very little and

returns to original size

after compression but

act by capillary action

-Water insoluble and spongy in

nature so get porous tablet

Sodium starch glycolate

Explotab®

Primogel®

Cross-linked

starch

-Swells 7-12 folds

in < 30 seconds

-Swells in three dimensions and

high level serve as sustain

release matrix

Alginic acid NF Satialgine® Cross-linked

alginic acid

-Rapid swelling in

aqueous medium

or wicking action

-Promote disintegration in

both dry or wet

granulation

Soy Polysaccharides Emcosoy® Natural

super

disintegrant

-Does not contain any starch or

sugar. Used in Nutritional

products.

Calcium silicate -Wicking action Highly porous, Optimum

concentration is between 20-



40%

Methods for preparing solid dispersions

Several approaches have been attempted for the preparation of solid dispersion, to improve the solubility and

dissolution characteristics of poorly water-soluble drugs which include-

Spray drying

In this method drug & carrier is dissolved in a volatile organic solvent with help of magnetic stirrer to get a

clear solution and solvent is evaporated at 400C under reduced pressure by using vacuum evaporator, obtained

mass is dried in a dessicator over anhydrous calcium chloride for 1-2 days depending on the removal rate of

solvent. The product is crushed, pulverized & sieved through a suitable mesh number sieve [22].

Fusion method

The fusion process is technically the less difficult method of preparing dispersions provided the drug and carrier

are miscible in the molten state. This process employs melting of the mixture of the drug and carrier in metallic

vessel heated in an oil bath, immediately after fusion, the sample are poured onto a metallic plate which is kept

at ice bath [22].

Solvent evaporation

Solid dispersions prepared by solvent removal process were termed by Bates as “coprecipitates”. In this method

drug &carrier is dissolved in a volatile organic solvent with help of magnetic stirrer toget a clear solution and

solvent is removed at room temperature, obtained mass is dried in a dessicator over anhydrous calcium chloride

for 1-2 days depending on the removal rate of solvent at room temperature. The product is crushed, pulverized

& sieved through a suitable mesh number sieve [22].

Hot-melt extrusion

Hot melt extrusion approach represent the advantageous mean of preparation of Solid Dispersion by using the

twin screw hot melt extruder where only thermo stable components are relevant. The extruder consists of a

hooper, barrel, a die, a kneading screw and heaters. The physical mixture is introduced into the hopper that is

forwarded by feed screw and finally is extruded from the die [22]. Melt extrusion is essentially the same as the

fusion method except that intense mixing of the components is induced by the extruder [23].



Particle size reduction

Conventional methods of particle size reduction, such as comminution and spray drying, rely upon mechanical

stress to disaggregate the active compound. The critical parameters of comminution are well-known to the

industry, thus permitting an efficient, reproducible and Economic means of particle size reduction [22].

Supercritical fluid (SCF) processes

Supercritical fluid methods are mostly applied with carbon dioxide (CO2), which is used as either a solvent for

drug and matrix or as an anti-solvent. When supercritical CO2 is used as solvent, matrix and drug are dissolved

and sprayed through a nozzle, into an expansion vessel with lower pressure and particles are immediately

formed. The adiabatic expansion of the mixture results in rapid cooling. This technique does not require the use

of organic solvents and since CO2 is considered environmentally friendly, this technique is referred to as

solvent free [23].

Kneading

In this method a mixture of drug and carrier is wetted with water and kneaded thoroughly for 30 minutes in a

glass mortar. The paste is dried under vacuum for 24 hours. Dried powder is passed through sieve no. 60 and

stored in desiccators [22].

Inclusion Complexes

Drug- cyclodextrin complexes are commonly formed through either supersaturating a cyclodextrin solution with

drug and mildly agitating the solution for an extended period of time, or adding a mass of drug to a cyclodextrin

and solvent slurry and ‘kneading’ to produce a paste which is then dried and sieved [22].

Direct Capsule filling

Direct filling of hard gelatin capsules with the liquid melt of solid dispersions avoids grinding-induced changes

in the crystallinity of the drug. The filling of hard gelatin capsules has been feasible in molten dispersions of

triamterene-PEG 1500 using a Zanasi LZ 64 capsule-filling machine (Zanasi Co, Bologna, Italy). This molten

dispersion forms a solid plug inside the capsule on cooling to room temperature, reducing crosscontamination

and operator exposure in a dust-free environment, better fill weight and content uniformity was obtained than

with the powder-fill technique [24].

Electrostatic Spinning Method



In this process, a liquid stream of a drug/polymer solution is subjected to a potential between 5 and 30 kV.

When electrical forces overcome the surface tension of the drug/polymer solution at the air interface, fibers of

submicron diameters are formed [24].

Surface-active Carriers

A surface-active carrier may be preferable in almost all cases for the solid dispersion of poorly water-soluble

drugs. The surface-active and self-emulsifying carriers for solid dispersion of poorly water-soluble drugs have

been of great interest in recent years. Two of the important surface-active carriers are utilizes for the preparation

of solid dispersions that is Gelucire 44/14 and Vitamin E R-alpha-tocopherylpolyethylene glycol 1000 succinate

(TPGS). Gelucire 44/14 (Gattefosse´ Corp, Gennevilliers, France) has commonly been used in solid dispersion

for the bioavailability enhancement of drugs [22].

Summarizes the studies conducted recently using this technique in order to achieve higher bioavailability of the

poorly water soluble drugs

Following are the citations were worked on fast dissolving drug delivery system. Bhardwaj S. et al. formulated

and evaluated the fast dissolving tablet of Aceclofenac using various super disintegrates sodium starch glycolate

following by direct compression technique. It was concluded that the fast dissolving tablets of poor soluble drug

can be made by direct compression technique using selective super disintegrates showing enhanced dissolution,

taste masking and hence better patient compliance and effective therapy [25]. Gudas G. K. et al. prepared

formulation and evaluation of fast dissolving tablets of Chlorpromazine HCL. The tablets were prepared with

five superdisintegrantseg: Sodium starch glycolate, Crospovidone, Croscarmellose, L-HPC, Pregelatinised

starch. The blend was examined for angle of repose, bulk density, tapped density, compressibility index and

hausners ratio. The tablets were evaluated for hardness, friability, disintegration time, dissolution rate, drug

content. It was concluded that the fast dissolving tablets with proper hardness, rapidly disintegrating with

enhanced dissolution can be made using selected superdisintegrants[26]. Shinde A. K. et al. studied on

development and characterization of oral fast dissolving tablet of Nifedipine using camphor as a subliming

material. An attempt has been made to prepare fast dissolving tablets of nifedipine were prepared by wet

granulation technique using camphor as subliming agent and sodium starch glycolate together with

crosscarmellose sodium as superdisintegrants, flavor and sweetner impart the taste to the formulation. The

porous granules were compressed in to tablets by single punch tablet machine. Camphor was sublimed from the

tablet by exposing to vacuum drier at 60°c for 12 hrs. The present study demonstrated potentials for rapid

absorption, improved bioavailability, effective therapy and patient compliance [27]. Khemariya P. et al.

prepared and evaluated the mouth dissolving tablets of Meloxicam. The purpose of this study was to grow



mouth dissolve tablets of Meloxicam. Sublimation of camphor from tablets resulted in better tablets as

compared to the tablets prepared from granules that were exposing to vacuum. The systematic formulation

approach helped in understanding the effect of formulation processing variables [28]. Zade P.S. et al. studied

on Formulation, Evaluation and Optimization of Fast dissolving tablet containing Tizanidine Hydrochloride.

Tizanidine HCL is a centrally acting α-2 adrenergic agonist musle relaxant. It is slightly bitter in taste. In a

present study an attempt has been made to prepare bitterless fast dissolving tablet using Eudragit E 100 as a

taste masking agent. Mass extrusion was the technique used for preparing taste masking granules. The tablet

was prepared with three super disintegrants e.g. sodium starch glycolate, crosscarmellose sodium and

crospovidone [29]. Madan J. et al. studied on fast dissolving tablets of Aloe Vera Gel for nutraceutical and

found the result of multiple regression analysis revealed that in order to obtain a fast dissolving tablets of the

aloe vera gel, an optimum concentration of mannitol and a higher content of microcrystalline cellulose should

be used. It also showed the potential of experiment design in understanding the effect of formulation variables

on the quality of fast dissolving tablets [30]. Mahamuni S.B. et al. prepared Fast Dissolving Tablets of

Promethanzine HCL with Masked Bitter Taste. Fast dissolving tablets were prepared using taste-masked

granules and a mixture of excipients containing optimized level of Microcrystalline cellulose (Avicel PH-101)

and starch and found the result the dissolution rate was significantly improved with FDT formulation with taste

[31]. Jain C. P. et al. studied on formulation and evaluation of fast dissolving tablets of Valsartan prepared by

direct compression using different superdisintegrants. Effect of disintegrant on disintegration behavior of tablet

in artificial saliva, pH 5.8 was evaluated. Wetting time of formulations containing Crospovidone was least and

tablets showed fastest disintegration [32]. Parmar R.B. et al. prepared domperidone (categories - anntimetic

drugs ) fast dissolving tablets used for treatment in adults and children in these formulation used ssg and

Avicel PH 102 by direct compression method and found result the use of super distintegrants for preparation

of fast dissolving tablets is highly effective and commercially feasible. This disintegration is reported to have

an effect on dissolving characteristics as well. Prepared fast-dissolving tablet get dispersed in the month quickly

and releases the drug early as compared to its formulated conventional tablets [33]. Singh S. K. et al. prepared

fast disintegrating combination tablets of Omeprazole and domperidone using mannitol as diluents and sodium

saccharin as sweetening agent along with three different levels of disintegrant. The superdisintegrant used in

this study were Kollidon CL, Ac-Di-Sol and SSG. The tablets were evaluated for weight variation, hardness,

friability, wetting time, water absorption ratio, disintegration time, and dissolution study. Using the same

excipients, the tablets were prepared by direct compression and were evaluated in the similar way [34]. Kumar

D. N. et al. studied on design of fast dissolving granisteron HCL tablets using novel co-processed

superdisintegrants consisting of crospovidone and crosscarmellose sodium in the different ratios (1:1, 1:2 &

1:3). Fast dissolving tablets of granisetron hydrochloride were prepared using the above co-processed



superdisintegrants and evaluated for pre-compression and postcompression parameters.Short-term stability

studies on promising formulation indicated that there were no significant changes in drug content and in vitro

dispersion time (p<0.05)[35]. Patel B. et al. developed and performed in vitro evaluation of fast dissolving

tablets of glipazide. Direct compression method is used for the preparation of tablets. Two

superdisintegrantsviz, crospovidone and croscarmellose sodium (4%, 5%, 6%) with different binders viz, pvp k-

30 and pregelatinized starch (3%) were used. The prepared batches of tablets were evaluated for hardness,

friability, weight variation, disintegration, wetting time, drug content and in vitro dissolution studies. Based on

evaluating parameters, Formulation prepared by using 5% croscarmellose sodium with 3% PVP K30 was

selected as optimized formulation [36]. Yadav I. K. et al. studied on formulation, evaluation and optimization of

fast dissolving tablets containing nimesulide micropellets. The disintegration time and dissolution profile of the

FDTs of Nimesulidemicropellets were compared with the FDTs containing plain Nimesulide was concluded

that FDTs prepared with Nimesulidemicropellets are fast disintegrating and have improved dissolution profile

than FDTs prepared with plain Nimesulide[37]. Rangasamy M. et al. studied on design and evaluation of the

fast dissolving tablet of Terbutaline Sulfate. An attempt was made to improve the onset of action of

bronchodilator used commonly in the treatment of asthma. Fast dissolving tablets of terbutaline sulfate were

prepared by direct compression method after incorporating superdisintegrants such as Explotab, Ac-Di-Sol and

Polyplasdone XL in different concentrations [38]. Rao N. G. R. et al. developed and evaluated Carbamazepine

fast dissolving tablets prepared with a complex by direct compression technique with β-cyclodextrin complexes

using various super disintegration like Indion-414, croscarmellose sodium, crospovidone and sodium starch

glycolate. The rate of absorption and/or the extent of bioavailability for such a poor soluble drug is controlled

by rate of dissolution in gastrointestinal fluids. Hence, to enhance the solubility of the drug, a complex of

Carbamazepine was prepared with β-cyclodextrin and this complex was compressed into tablets. Drug release

showed time between the ranges of 4 and 12 min [39]. Narmada G. Y. et al. studied on formulation, evaluation

and optimization of dissolving tablets containing Amlodipine Besylate by sublimation method. Sublimation

method was adapted to prepare the tablets by using a 23 full factorial design. FT-IR and D.T.A studies revealed

that there was no physic-chemical interaction between amlodipine besylated and other excipients. All

formulation are evaluated for pre-compression and post-compression parameters. The result indicate that the

optimized tablet formulation provides a short DT of 8 s with sufficient crushing and acceptable friability [40].

Nagar M. et al. performed formulation, evaluation and comparision of fast dissolving tablet of Nimesulide by

using crospovidone as superdisintegrant. Fast dissolving tablets of Nimesulide were prepared by direct

compression method. The study was performed by incorporating the superdisintegrant (crospovidone) in 2%,

4%, 8%, 12% concentration respectively. Optimized batch formulation was compared with the available

marketed preparation [41]. Doijad R.C. et al. performed a comparative study on mouth dissolving tablets of



granistetron with different super disintegrants: formulation and evaluation. Tablets were prepared by wet

granulation method. PVP K-32 in isopropyl alcohol is used as binder and granules were compressed on a

cadmach single stroke punch machine [42]. Sharma S. et al. studied on formulation and characterization of fast

dissolving tablet of promethazine theoclate. Fast dissolving tablets Promethazine theoclate were prepared by

direct compression method after incorporating superdisintegrants Ac-Di-Sol, sodium starch glycolate (SSG),

and crospovidone in different concentrations [43]. Mundada A.S. et al. studied on formulation and evaluation of

dispersible taste masked tablet of roxithromycin. Roxithromycin is a broad spectrum, semi-synthetic macrolide

antibiotic, having bitter taste. In this study, an attempt has been made to mask the bitter taste of roxithroycin by

complexation technique. Weak cation exchange resins Indion 214 and Amberlite IRP64, polymer carbopol

934P were used in formulation of complexes with the drug. The complexes were evaluated for bulk density,

angle of repose, taste masking, and invivo drug release. In vitro drug release studies showed more than 80%

drug release from the optimized formulation within 30 min. amberlite IRP64 was found to be found better

complexing agent for masking the bitter taste of roxithromycin [44]. Patel N. V. et al. studied on formulation

design of oxcarbazepine fast-release tablets prepared by melt granulation technique. Melt granulation technique

is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The

remarkable enhancement of drug dissolution rate of the granules in comparison to physical mixtures and pure

drug, but no significant differences were found between the dissolution profiles of the granulates containing

lactose or starch [45]. Fini A. et al. prepared eight formulation of ibuprofen in the form of orally disintegrating

tablets. For preventing bitter taste and side effects of the drug, and drug associated with Phospholipon 80H,a

saturated lecithin, by wet granulation and found result the combined action of the hydrophobic lecithin and the

coating delay the release of drug from tablets with respect to when it was free from or in the form of simple

granules . By an appropriate combination of excipient it was thus possible to obtain orally disintegrating tablets

and a delayed release of ibuprofen using simple and conventional techniques [46]. Patel D. M. et al. performed

optimization of fast dissolving Etoricoxib tablets prepared by sublimation technique. Granules containing

etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique.

Menthol was sublimed from the granules by exposing the granules to vacuum. From the results, it was

concluded that fast dissolving tablets with improved etoricoxib dissolution could be prepared by sublimation of

tablets containing suitable subliming agent [47]. Chakraborty S. et al. studied on comparative effect of natural

and synthetic superdisintegrants in the formulation of fast dissolving tablets. The effect of a natural

superdisintgrant vis-à-vis isolated mucilage of Plantagoovata and synthetic superdisintegrants like sodium

starch glycolate (SSG) and croscarmellose sodium (Ac-Di-Sol) were compared in the formulations of fast

dissolving tablets. Fast dissolving tablets of Aceclofenac (modal drug) were prepared by direct compression

method using microcrystalline cellulose as direct compressible vehicle. The present study revealed that this



natural superdisintegrantPlantagoOvata mucilage showed better disintegrating property than the most widely

used synthetic super disintegrants like SSG and Ac-Di-Sol in the formulation of fast dissolving tablets [48]. Jha

S. K. et al. performed the formulation and evaluation of melt-in-mouth tablets of haloperidol. All the

formulation had disinitegration time less than 30 s and release maximum amount of drug by 12 min.

formulation containing higher concentration of crospovidone decrease disintegration time and optimize the drug

release. The most satisfactory formulation was found to be stable during the stability studies conducted as per

ICH guidelines QIC, as it showed no significant changes (P<0.05) in the physicochemical properties,

disintegration time and in vitro drug release[49]. Malke S. et al. prepared the formulation and evaluate the

Oxcarbazepine fast dissolve tablets. Oxacarbazepine is a new anticonvulsant drug used as an first line treatment.

The present investigation was undertaken with a view to develop a fast dissolving tablets of oxcarbazepine

which offers a new range of product having a desired characterstics and intended benefits. A modified

disintegration method was used for studying disintegration. An effective, pleasant tasting and stable formulation

containing 12% Ac-Di-sol, 25% Avicel PH 102 and 8.5% starch as a binder was found to have a good hardness

of 4-4.5 kg/cm2, disintegration time of 28±5s and drug release of not less than 90% within 30 min [50]. Sharma

S. et al. studied on development and evaluation of carvedilol fast dissolving tablets using superdisintegrant and

solid dispersion technique. Carvedilol is a oral hypertensive agent, with problems of variable bioavailability and

bioinequivalence related to its poor water solubility. This work investigated the possibility of developing

carvedilol tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in

polyethylene glycol [51]. Purvis T. et al. prepared rapidly dissolving repaglinide powders produced by ultra-

rapid freezing process, investigate the influence of excipient type on repaglinide stability.Repaglinide

compositions containing different types and levels of excipients and different drug potencies (50%-86%) were

produced by the URF technology. Forced degradation of repaglinide was conducted under stressed conditions

(eg, elevated temperature, exposure to peroxide) to determine the stability of the drug in such environments.

The solubility of repaglinide increased as a function of increasing pH; therefore, incorporation of an alkalizing

agent into the URF formulations increased the drug’s solubility [52]. Sarasija S. et al. prepared and evaluate

mouth dissolving tablets of Salbutamol Sulphate. Fast dissolving tablets of salbutamol sulphate were prepared

using sublimation ingredients. Selection of the filler also had an important role in deciding the disintegration

time. Evaluation of the tablets showed that all the tablets were found to be within official limits and the

disintegration time for the formulations ranged from 5 s to 40 s. amongst all, the formulation containing

microcrystalline cellulose and ammonium bicarbonate showed the least disintegration time of 5 s [53]. Kumar

R. et al. studied on formulation and evaluation of mouth dissolving tablets of metformin HCL prepared by

direct compression method using various superdisintegrants such as, Ac-Di-Sol, Explotab, Polyplasdone, Starch

1500 and L-HPC in different concentrations using different diluents. The TLC, IR and DSC studies show that



there was no significant evidence of interaction between the drug and excipients. The prepared tablets were

evaluated for hardness, friability, weight variation, wetting time, water absorption ratio, in vitro and in vivo

disintegration time and in vitro drug release. Tablets containing crosscarmellose and crosspovidone at 5% w/w

concentration showed disintegration time of less than 60s along with rapid in vitro dissolution (95% drug

release at 5 min) Avicel (PH 102) was the best diluent amongst the other diluents used in the formulation [54].

Patel M. M. et al. prepared fast dissolving valdecoxib tablets containing solid dispersion of valdecoxib with

mannitol, polydthylene glycol 4000, and polyvinyl pyrolidone K-12, were prepared with a view to increase its

water solubility. Valdecoxib solid dispersion with polyvinyl pyrolidone K-12 showed maximum drug release

[55]. Sammour O. A. et al. formulated and optimized of mouth dissolve tablets containing Rofecoxib solid

dispersion prepared with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. For the

preparation of rofecoxib mouth dissolve tablets, it’s 1:9 solid dispersion with PVP K30 was used with various

disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of

disintegration time and percentage friability, a 32 randomized full and reduced factorial design was used to

optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed

that dispersion of the drug in the polymer considerably enhanced the dissolution rate. Concerning the

optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a

higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets [56]. Jani G.K. et al.

studied on Formulation and Evaluation of New Superdisintegrants for Dispersible Tablets. Effect of addition of

distilled water and its temperature on swelling characteristics of agar and gum karaya was investigated with a

goal to prepare a natural new modified form of agar and gum karaya. Formulation containing modified agar

(7.5% w/w) and gum karaya (7.5% w/w) showed faster disintegration than those of formulation containing

parent agar and gum karaya. The study revealed that modified agar and gum karaya could be used as super

disintegrants at 7.5% w/w concentration levels compared to synthetic super disintegrant Ac-Di-Sol [57]. Gohel

M. et al. formulated design and optimize mouth dissolve tablets of nimesulide using vacuum drying technique.

Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation

technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were

then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. In the investigation, a

32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of

camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a

rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and

a higher percentage of crospovidone[58].Gilis et al. studied on a fast dissolving tablet for oral administration

comprising as an active ingredient a therapeutically effective amount of galanthaminehydrobromide (1:1) and a

pharmaceutically acceptable carrier, characterized in that said carrier comprises a spray dried mixture of lactose



monohydrate and microcrystalline cellulose (75:25) as a diluent, and a disintegrant; and with a direct

compression process of preparing such fast dissolving tablets [59]. Fausett H. et al. studied on evaluation of

quick disintegrating calcium carbonate tablets prepared by direct compression and compare it with

commercially available calcium tablets. The disintegration and dissolution properties of the tablets were studied

using USP methodology. The dissolution studies showed that all formulation released 100% of the elemental

calcium in simulated gastric fluid in less than 20 minutes. In summary, this study clearly demonstrated that

quick disintegrating calcium carbonate tablets can be formulated without expensive effervescence technology

[60]. Kumar S et al. concluded that crospovidone and crosscarmellose sodium are better disintegrants for

formulation of MDTs of Sildenafil citrate. Over all result suggests that 2-8% of disintegrant concentration is

suitable for the preparation of Sildenafil citrate, MDTs tablet the best allow combination of two

superdisintegrant CCS and CRP (Batch B10) release 81.82% drug, Show of DT 30 sec [61].

Conclusion

Fast dissolving drug delivery system have better patient compliance and may offer improved biopharmaceutical

properties, improved efficacy and better safety compared with conventional oral dosage forms. Today, fast

disintegrating tablets are more widely available as over-the-counter products for the treatment of allergies, cold

and flu symptoms. The future potential for these products is promising because of the availability of new

technologies combined with strong market acceptance and patient demand. Future possibilities for

improvements in Rapid disintegrating and drug delivery are bright, but the technology is still relatively new.

The research is still going on. More products need to be commercialized to use this technology properly. Mouth

dissolving films are intended for the application in the oral cavity and they are innovative and promising dosage

form especially for use in pediatrics and geriatrics. Mouth dissolving films have several advantages over

conventional dosage forms and fast dissolving tablets. Fast dissolving tablets have gained considerable attention

as a preferred alternative to conventional tablets and capsules due to better patient compliance. Preparing

pharmaceuticals acceptable dosage form demands clear understanding details about the Fast dissolving tablet or

Mouth dissolving tablet. This review discusses the method of preparation, properties, advantages, mechanisms;

drugs to be incorporated in the fast dissolving drug delivery system and evaluation of the mouth dissolving

tablet are emphasized.

Swallowing a pill is a major difficulty encountered in case of geriatric and pediatric patient which leads to poor

patient compliance due to unpalatable taste of drug. Fast dissolving tablets can be prepared by using various

conventional methods like direct Compression, wet granulation, moulding, spray drying, freeze drying, and

sublimation method and by using different type of superdisintegrants like Cross linked 93

carboxymelhylcellulose (Croscarmeliose),Sodium starch glycolate (Primogel, Explotab), Polyvinylpyrrolidone



(Polyplasdone) etc. This review discusses the method of preparation, properties, advantages, disadvantage,

characterization ,mechanisms; drugs to be incorporated in the mouth dissolving tablet and evaluation of the

product and future trend of the mouth dissolving tablet.

REFERENCES

1. Chang R.K., Guo X., Burnside B.A., Couch R., Pharm Tech. 2000, 24(6), 52-58.

2. Seager H., J Pharm and Pharmacol.1998, 50, 375-382.

3. Bradoo R., Shahani S., Poojary S., Deewan B., and Sudarshan S., J Am Med Assoc India. 2001, 4(10), 27-31.

4. Habib W., Khankari R., Hontz J., Crit Rev Ther Drug Carrier Syst. 2000,17,61-72.

5. Divate S., Kavitha K., Sockan G.N., 2011, 6 (2), 18-22.

6. Bhowmik D., Chiranjib B., Chandira P.K., J Chem Pharm Res. 2009, 1(1), 163-177.

7. Biradar S.S., Bhagavati S.T., Kuppasad I.J., Internet J Pharmacol. 2006, 4(2).

8. Drews J., Quest of Tomorrow's Medicines. Springer-Verlag; New York, 1999, 59-68.

9. Reddy L.H., Ghosh B.R., Ind J Pharm Sci. 2002, 64(4), 331-336.

10. Anon., Flavors and Flavoring, Int J Pharm Compounding. 1997, 1, 90-92.

11. Kuchekar B.S., Badhan A.C., Mahajan H.S., Pharma Times. 2003, 35, 7-9.

12. Sharma S., pharmainfo.net. 2008, 6(5).

13. Prajapati BG, Ratnaker N., Int J Pharma Tech Res. 2009, 1(3), 790-798.

14. Seager H., J Pharm and Pharmacol. 1998, 50, 375-382.

15. Vishwkarma D.K., Tripathi A.K.B, Yogesh P., Maddheshiya B., Journal of Global Pharma Technology. 2011,

3(1), 1-8.

16. Profile Resources at Business.com. Cima Labs - Profile. 2001, 27, 5.

17. Kumari S., Visht S., Sharma P.K., Yadav R.K., Journal of Pharmacy Research. 2010,, 3(6),1444-1449

18. Patel P.B., Chaudhary A., Gupta G.D., Pharmainfo.net. 2006, 4(4).

19. Shukla D., Chakraborty S., Singh S., Mishra B., Sci Pharm. 2009, 309-326.

20. Bhandari S., Mittapalli R.K., Gannu R., Rao Y.M. Asian J Pharma, 2008, 2-11.

21. Leuner C., Dressman J.,European J of Pharm and Biopharm. 2000, 50, 47-60.

22. Patidar K., Soni M., Sharma D.K., Jain S.K., Drug Invention Today. 2010, 2(7), 349-357.

23. Dhirendra K., Lewis S., Udupa N., Atin K., Pak J Pharm Sci. 2009, 234-246.

24. Karanth H., Shenoy V.S., Murthy R.R., AAPS Pharm Sci Tech. 2006, 7(4), 87.

25. Bhardwaj S., Jain V., Jat R.C., Mangal A., Jain S., Int j of Drug Delivery. 2010, 2, 93-97.

26. Gudas G.K., Manasa B., Rajesham V.V., Kumar S.K., Kumari J.P., J Pharm Sci Tech. 2010, 2(1), 99-102.

27. Shinde A.K.J., Waghule A.N., Paithane A., More H.N., Res J Pharm Bio and Chem Sci .2010, 1(1),46-50.



28. Khemariya P., Gajbhiye K. R., Vaidya V.D., Jadon R.S., Mishra S., Shukla A., Bhargava M., Singhai S.K.,

Goswami S., Int J Drug Delivery. 2010, 2, 76-80.

29. Zade P.S., Kawtikwar P.S., Sakarkar D.M., Pharm Tech. 2009, 1(1), 34-42.

30. Madan J., Sharma A.K., Singh R., Tropical J Pharm Res. 2009, 8(1), 63-70.

31. Mahamuni S.B., Shahi S.R., Shinde N.V., Agrawal G.R., Int J Pharm Res and Development. 2009, 7,1-18.

32. Jain C.P., Naruka P.S., Int J Pharmacy and Pharm Sci. 2009, 1(1), 219-226.

33. Parmar R.B., Baria A.H., Tank H.M., Faldu S.D., Int J Pharm Tech Res. 2009, 1(3), 483-487.

34. Singh S.K., Mishra D.N., Jassal R., Soni P., Asian J Pharm and Clin Res. 2009, 2(3), 74-82.

35. Kumar D.N., Raju S.A., Shirsand S.B., Para M.S., J Biosci Tech. 2009, 1(1).

36. Patel B., Patel D., Parmar R., Patel C., Serasiya T., Sanjan S.D., Int J Pharmacy and Pharm Sci. 2009, 1(1), 145-

150.

37. Yadav I. K., Jaiswal D., Singh H.P., Chandra D., Jain D.A., Int J Chem Tech Res.2009, 1(4), 910-914.

38. Rangasamy M., Ayyasamy B., Raju S.K., Gummadevelly S., Asian J Pharm. 2009, 215-217.

39. Rao N.G.R., Patel T., Gandhi S., Asian J Pharm. 2009, 97-103.

40. Narmada G.Y., Mohini K., Prakash R.B., Gowrinath D.P., Kumar K.S., ARS Pharm. 2009, 50(3),129-144.

41. Nagar M., Singhai S.K., Chopra V., Mandage K., Int J Pharm Sci and Drug Res. 2009, 1(3), 172-175.

42. Doijad R.C., Manvi F.V., Khalandar K.S.D., Int J Pharmacol, 2008, 5(2).

43. Sharma S., Gupta G.D., Asian j Pharm. 2008,70-72

44. Mundada A.S., Meshram D.R., Bandale H.B., Bhalekar M.R., Avari J.G., Asian j pharm. 2008, 116-119.

45. Patel N.V., Chotai N.P., Patel M.P., Asian J pharm. 2008, 22-25.

46. Fini A.,Bergamante V., Ceschel G.C., Ronchi C., Euro J of Pharm and Biopharm. 2008, 69, 335-341.

47. Patel D.M., Patel M.M., Ind J Pharm Sci. 2008, 70(1), 71-76.

48. Chakraborty S., Khandai M., Singh S.P., Patra N.C., Int J Green Pharmacy. 2008, 2(1), 22-25.

49. Jha S.K., Vijaylakshami P., Karki R., Goli D., Asian J Pharm. 2008, 255-260.

50. Malke S., Shindaye S., Kadam V.J., Ind J Pharm Sci. 2007, 69(2), 211-214.

51. Sharma S., Gupta G.D., Jain C.P., Naruka P.S., Development and Evaluation of Carvedilol Fast Dissolving

Tablets using Superdisintegrates and Solid Dispersion Technique, The Pharm Rev. 2007.

52. Purvis T., Mattucci M.E., Crisp M.T., Keith Johnston K.P., Williams R.O., AAPS Pharm Sci Tech. 2007,

8(3),58.

53. Sarasija S., Pandit V., Joshi H. P., Ind J Pharm Sci. 2007, 69(3), 467-469.

54. Kumar R., Shirwaikar A.A., Shirwakar A., Mahalaxmi R., Prabhu S.L., Int J Pharm Excip. 2006, 86-92.

55. Patel M.M., Patel D.M., Ind J Pharm Sci. 2006, 68(2), 222-226.

56. Sammour O.A., Hammad M.A., Megrab N.A., Zidan A.S., AAPS Pharm Sci Tech. 2006, 7(2),55.



57. Jani G.K., Goswami J.M., Prajapati V.D., Zinzuwadia M.M., Joshi B.R., Dabhi A.S., Int J Pharm Excip. 2005,

37-43.

58. Gohel M., Patel M., Amin A., Agrawal R., Dave R., Bariya N., AAPS Pharm Sci Tech, 2004, 5(3): 36.

59. Gilis, C. D., Fast-dissolving galanthaminehydrobromide tablet, 2002, US patent NO., 6358527.

60. Fausett H., Charles G. J., Dash A.K., AAPS PharmSci Tech. 2000, 1(3), 20.

61. Kumar S., Sachdeva M., Bajpai M., Journal of Pharmaceutical Science and Technology. 2010, 2 (4), 202-206.

AN OVERVIEW ON FAST DISSOLVING DRUG DELIVERY SYSTEM

Documents