A Review on mouth dissolving tablet

A REVIEW ON MOUTH DISSOLVING TABLET

PROJECT SUBMITTED
IN THE PARTIAL FULFILLMENT OF THE DEGREE OF
BACHELOR OF PHARMACY
IN
THE FACULTY OF PHARMACEUTICAL SCIENCES
SAVITRIBAI PHULE UNIVERSITY OF PUNE

SUBMITTED BY
MR. ABHISHEK LAXMAN THALE
(Final Year B. Pharm)
GUIDE
ASST. PROF. MRS. SHRADDHA A. MUNDADA
(Dept. of pharmaceutical chemistry )

DR. NJ PAULBUDHE COLLEGE OF PHARMACY

SHANISHWAR NAGAR, VASANT TEKDI AHMEDNAGAR-41400
2023-24

CERTIFICATE
This is to certify that the project entitled “A Review On Mouth Dissolving Tablet” is a bonafide work of “Abhishek
Laxman Thale ” executed in the Department of Pharmaceutics” and submitted to the DR. N.J. Paulbudhe College of
Pharmacy Affiliated to Savitribai Phule Pune University of Pune in partial fulfillment of the requirement for the
completion of Practice School (BP706PS) of Final Year B. Pharm (SEM VII) Academic Year 2023 – 2024.

(Asst. Prof. Mrs. Shraddha A. Mundada)

( M. Pharma)College seal
Guide
 (Dr. Shyam Panga )(Dr. Nilesh Jadhav )
Head of Department Principal

Practice School Report Approval for B Pharm

This Practice School report entitled ‘A Review On Mouth Dissolving Tablet’ by Abhishek Laxman Thale is approved
for consideration towards the completion of Practice School (BP706PS) of Final Year B.Pharm (SEM VII) Academic
Year 2023 – 2024.
.

Examiners

1.

2.

Date

Place
Index

Introduction:

The concept of MDS emerged to improve patient compliance This dosage forms rapidly disintegrate and/or dissolve
to release the drug as soon as they come in contact with saliva, thus obviating the need for water during
administration, an attribute that makes them highly attractive for pediatric and geriatric patients. Difficulty in
swallowing conventional tablets and capsules is common among all age groups, especially in elderly and dysphagic
patients (1)

This disorder of dysphagia is associated with many medical conditions including stroke, and Parkinson’s disease.
AIDS, thyroidectomy, head and neck radiation therapy, and other neurological disorders including cerebral palsy (2-
51

One study showed that 26% out of 1576 patients experienced difficulty in swallowing tablets due to their large size,
followed by their surface, shape, and taste [4]

Elderly patients may find the administration of the conventional oral dosage forms difficult as they regularly require
medicines to maintain a healthy life [6, 7] Children may also have difficulty ingesting because of their
underdeveloped muscular and nervous systems [8]

The problem of swallowing tablets is also evident in traveling patients who may not have ready access to water [3]
Aforementioned problems can be resolved using Mouth Dissolving Tablets (MDT) MDTS are known by varna such
as "fast-melting, fast-dissolving, oral disintegrating or erodes, European Pharmacopoeia defines the term "or disperse"
as a tablet that can be placed in the mouth where M disperses rapidly before swallowing [9]

Suitable drug candidates for such systems include neuroleptics cardiovascular agents, and analgesics. antiallergics and
drugs for erectile dysfunction (10) MDTs disintegrate and/or dissolve rapidly in saliva: therefore, water is not required
during administration Some tablets are designed to dissolve in saliva 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 about one minute to disintegrate completely.
MDTs offer several advantages over other dosage forms like effervescent tablets, dry syrups, and chewing
gums/tablets, which are commonly used to enhance patient compliance Administering effervescent tablets/granules
and dry syrups involves unavoidable preparation that includes the intake of water. Elderly patients cannot chew large
pieces of tablets or gums and sometimes experience the bitter or unpleasant taste of the drug in the dosage form if the
taste masking coat ruptures during mastication.
LITERATURE REVIEW:

Fukami et al (2006), was prepared rapidly disintegrating tablets using glycine as a disintegrant They evaluated the
disintegration behavior of tablets in the oral cavity containing carboxymethyl cellulose showed the least wetting time
of 3 seconds with 4 kg hardness and showed the fastest disintegration due to excellent wetting property. They also
studied the effect of ethanzamide and ascorbic acid on disintegration time. The result shows that ethionamide does not
affect disintegration properties. However, the disintegration time increases with ascorbic acid.

Moen et al (2006), had developed a new fast-disintegrating Sumatriptan tablet to speed absorption and the onset of
effect compared with standard Sumatriptan tablets. Compared with placebo, pain relief was significantly greater with
Sumatriptan fast disintegrating tablets 100mg at 25- and 17-minutes following administration and with Sumatriptan
fast disintegrating tablets 50mg at 50- and 30-minutes following administration, to severe migraine

Mizumoto, et al, was prepared novel fast disintegrating tablets using commonly used sugar as low and high
compressible categories. They improved the compressibility of low compressible saccharides by coating the granules
with high compressible saccharides to enable fast disintegration changed the crystal habit by the process and achieved
sufficient hardness

Shirwaikar and Ramesh et al, had formulated Atenolol using super disintegrants such as sodium starch glycollate,
croscarmellose sodium (Ac-Di- sol), and crospovidone. The dry granulation method was used to prepare tablets.
Various physical parameters considered are water uptake studies, In vitro release, and stability profile. Ac-Di-sol
proved to be the best of the three super disintegrants and showed the highest water uptakes. There was no change after
the stability study of the tablets
Udupa et al, was reported the formulation, preparation, and evaluation of Nimesulide dispersible tablets by direct
compression method. The tablets were prepared using microcrystalline cellulose as a directly compressible vehicle,
and starch and sodium starch glycollate combination as a super disintegrant. The formulations were evaluated for
hardness, weight variation, uniformity of dispersion, drug content disintegration time, dissolution rate, and stability
studies. The optimized formula showed less disintegration time and more dissolution than a marketed product.

Mishra et al, had developed Ora-Solv technology. In this system, the active medicament is taste-masked by using an
effervescent disintegrating agent. Tablets were made by direct compression technique at low compression force to
minimize oral dissolution time.
Baldi and Malfertheiner et al, was prepared Lansoprazole fat integrating tables a new, patient-friendly, and more
convenient formulation of Lansoprazole, which can be taken with or without water It represents an innovative drug
delivery system, comprising enteric-coated micro granules of Lansoprazole compressed with an inactive, rapidly
dispersing matrix to form a tablet. Alternatively, the tablet can be swallowed with a drink of water Studies have shown
that the bioavailability of Lansoprazole fast disintegrating tablet is comparable to Lansoprazole capsules, at both 15
and 30 mg doses

Ahmed et al. 27 had developed Ketoprofen tablets which dissolve rapidly in the mouth, therefore needing not to be
swallowed. The solubility and dissolution rate of poorly water-soluble Ketoprofen was improved by preparing
lyophilized tablets (LT) of Ketoprofen using a freeze-drying technique. Results obtained from dissolution studies
showed that lyophilized tablets of Ketoprofen significantly improved the dissolution rate of the drug compared with
the physical mixture and the plain drug

Shenoy et al, had developed fast-dissolving tablets of Diclofenac sodium using direct compression after incorporating
super disintegrants such as cross-linked carboxy methyl cellulose, sodium starch glycolate, and cross-linked
crospovidone in different concentrations and evaluated the effect of their concentrations on the characteristics of fast
dissolving tablets mainly in terms of disintegration time and dissolution rate

Mutasem et al, was studied the effect of an increase in Epinephrine in fast disintegrating tablets. They used
microcrystalline cellulose and L-hydroxy propyl cellulose as a diluent in the ratio (9:1) and direct compression was
employed in the preparation of the tablets. Results showed that a linear increase in compression force resulted in a
linear increase in the disintegration and wetting time of formulations without epinephrine and an exponential increase
in disintegration time and wetting time for tablets containing Epinephrine.

Chandrasekhar et al, was reported the preparation and evaluation of a Nimesulide dispersible tablet using primo gel as
a dispersing agent with starch, lactose, and dicalcium phosphate as diluents. The tablets were prepared by wet
granulation method and compared with commercial dispersible tablets. The formulation with starch and lactose as
diluents showed faster and more rapid dissolution than conventional tablets, whereas the tablets with dicalcium
phosphate as diluent showed a lower dissolution rate.
Advantages of MDDS:

Ease of administration to patients who cannot swallow, such as the elderly, stroke victims, and bedridden patients:
patients who should not swallow, such as renal failure patients, and who refuse to swallow, such as pediatrics,
geriatric, and psychiatric patients [11, 12]

Patient compliance for disabled bedridden patients and for traveling and busy people who do not have ready access to
water. The good mouth feels property of MDS helps to change the basic view of medication as a "bitter pill.
particularly for pediatric patients due to the improved taste of bitter drugs

Convenience of administration and accurate dosing as compared to liquid formulations... The benefit of liquid
medication in the form of solid preparation. More rapid drug absorption from the pre-gastric area ie, mouth, pharynx,
and esophagus may produce rapid onset of action [12, 13). Pregastric absorption can result in improved
bioavailability, reduced dose, and improved clinical performance by reducing side effects [14]

New business opportunities: product differentiation, line extension, life-cycle management, the exclusivity of product
promotion, and patent-life extension [12. 13].

Ideal Properties of MDTs:

not require water to swallow and should dissolve or disintegrate in the mouth within a few seconds

allow high drug loading.

be compatible with taste masking and other excipients.

have a pleasing mouth feel.

leave minimal or no residue in the mouth after oral administration.

have sufficient strength to withstand the rigors of the manufacturing process and post-manufacturing handling.

exhibit low sensitivity to environmental conditions such as humidity and temperature

• Techniques of MDT Formulation:

The fast-dissolving property of the MDTs is attributed to the quick ingress of water into the tablet matrix resulting in
rapid disintegration. Hence, the basic approaches to develop MDT's include

• Maximizing the porous structure of the tablet matrix

Incorporating the appropriate disintegrating agent/agents.

• Using highly water-soluble excipients in the formulation (15)

So far, several techniques have been developed based on different principles. The resulting dosage forms vary on
grounds like mechanical strength of the final product, drug and dosage form stability, mouth feels, taste, rate of
dissolution and absorption from saliva, swallowability, and overall bioavailability.

Various manufacturing techniques for MDS include:

1. Lyophilization

2. Moulding

3. Direct Compression

4. Cotton Candy Process

5. Spray Drying

6. Sublimation

7. Mass Extrusion

8. Canonization

9. Fast Dissolving Films

Freeze-Drying or Lyophilization:

In the freeze-drying process, the water is sublimed from the product after it is frozen. This technique forms the basis
of Zydis, Quicksolv, and Lyoc technologies which are used to manufacture MDTs. Jaccard and Leyder used
lyophilization to develop an oral formulation that not only dissolved rapidly but also exhibited improved
bioavailability of several drugs such as spironolactone and troleandomycin [14). Corveleyn and Remon studied
various formulations and process parameters by using hydrochlorothiazide as a model drug [17, 18).

Zydis technology (ZT) is a patented technique [13, 19-21], which has been used for drugs like famotidine loperamide,
piroxicam, oxazepam, lorazepam, domperidone, brompheniramine, olanzapine, ondansetron, and rizatriptan. Thirteen
products are currently available in the market, which had been manufactured using this technology (22). In the U.S.,
the MDT products available are Claritin Reditab, Dimetapp Quick Dissolve, Feldene Melt, MaxaltMLT, Pepcid RPD,
Zofran ODT, and Zyprexa Zydis. In the worldwide market, Zydis formulations are also available for oxazepam,
lorazepam, loperamide, and enalapril [23].

ZT utilizes a unique freeze-drying process to manufacture finished dosage units which significantly differ from
conventional oral systems [24]. The process involves the following steps:

Stage 1 bulk preparation of an aqueous drug solution or suspension and its subsequent precise dosing into pre-formed
blisters. It is the blister that actually forms the tablet shape and is, therefore, an integral component of the total product
package,

Stage 2 passes the filled blisters through a specially designed cryogenic freezing process to control the ultimate size of
the ice crystals which ensures that the tablets possess a porous matrix to facilitate the rapid disintegration property.
These frozen units are then transferred to large-scale freeze dryers for the sublimation process, where the majority of
the remaining moisture is removed from the tablets.

Stage 3-sealing the open blisters using a heat-sealing process to ensure stability and protection of the product

from varying environmental conditions.

Lyoc is a porous and solid galenic form obtained by lyophilization of an oil-in-water emulsion placed directly in the
blister alveolus [14, 25). Its unusual properties are the result of its unique method of preparation, which involves
freezing a thickened (paste-like) emulsion containing the active as bulk or as coated microparticles. This product is
capable of accommodating high doses and disintegrates rapidly but possesses poor mechanical strength.

Quicksilver is a porous solid form obtained by freezing an aqueous dispersion/solution of the drug-containing matrix
and then drying it by removing the water using an excess alcohol (solvent extraction) [26]. The final form
disintegrates very rapidly but is limited to low drug content and can be used only for those drugs that are insoluble in
the extraction solvent. The ideal drug characteristics required for this technology are relatively low aqueous solubility,
fine particle size < 50 µm (27, 28), and good aqueous stability in the suspension

The maximum drug loading capacity for water-insoluble and soluble drugs are 400 mg and 60 mg. respectively [12,
27)

The primary problems associated with water-soluble drugs are the formation of eutectic mixtures resulting in freezing-
point depression and the formation of a glassy solid on freezing which might collapse on drying due to loss of
supporting structure during the sublimation process 112, 13, 27]. MDTs manufactured using a lyophilization process,
usually contain excipients like polymers (eg, gelatin, alginates, and dextrin) to provide strength and rigidity to tablets,
polysaccharides (eg, mannitol and sorbitol) to impart crystallinity and hardness to the matrix and to improve
palatability, collapse protectants (e.g., glycine) to prevent the product from shrinking in its packaging during
manufacturing or storage; flocculating agents (e.g., xanthan gum and acacia) to provide a uniform dispersion of drug
particles, preservatives (eg. parabens) to prevent microbial growth; permeation enhancers (e.g., sodium lauryl sulfate)
to improve transmucosal permeability. pH adjusters (e.g. citric acid etc.) to optimize chemical stability, flavors, and
sweeteners to improve patient compliance and water to ensure the formation of porous units.

Advantages

The major advantage of using this technique is that the tablets produced by this technology have very low
disintegration time and have great mouthfeel due to a fast melting effect

Disadvantages

Although it is a fairly routine process, lyophilization has some disadvantages like it is a relatively expensive and time-
consuming process. Furthermore, the product obtained is poorly stable and fragile, rendering conventional packaging
unsuitable.

Tablet Moulding:

Molded tablets invariably contain water-soluble ingredients due to which the tablets dissolve completely and rapidly.
Following are the different tablet molding techniques

Compression Moulding Process This manufacturing process involves moistening the powder blend with a
hydroalcoholic solvent followed by pressing it into mold plates to form a wetted mass (compression molding). The
solvent is then removed by air drying, a process similar to the manufacture of tables triturates. Such tablets are less
compact than compressed tablets and possess a porous structure that hastens dissolution [15]

Heat-Moulding Process:

The heat-molding process involves setting the molten mass containing a dispersed drug [29]. This process uses agar
solution as a binder and blister packaging as well as a mold to manufacture the tablet. A suspension containing drug,
agar, and sugar is prepared followed by pouring the suspension into the blister packaging well, solidifying the agar
solution at room temperature to form a jelly and finally drying at approximately 30 C under vacuum.

Molding by Vacuum Evaporation without Lyophilization

This process involves pouring the drug excipient mixture (in the form of a slurry or paste) into a mold of desired
dimension, freezing the mixture to form a solidified matrix, and finally subjecting it to vacuum drying at a
temperature within the range of its collapse temperature and equilibrium freezing temperature This results in the
formation of a partially collapsed matrix. This method differs from the lyophilization technique, as in the former the
evaporation of free unbound solvent occurs from a solid through the liquid phase to a gas, under controlled conditions,
instead of the sublimation which takes place in the latter process Unlike lyophilization, vacuum drying helps to
densify the matrix and thereby improves the mechanical strength of the product. Pebley et al. [30], evaporated the
frozen mixture containing a gum (eg, acacia, carrageenan, guar, tragacanth, or xanthan), a carbohydrate (e.g.,
dextrose, lactose, maltose, mannitol, or maltodextrin) and solvent in a tablet-shaped mold to design an MDT with a
disintegration time of about 20- 60 secs.

Tablets produced by molding are solid dispersions. The drug, depending on its solubility in the carrier, exists either as
discrete particles or microparticles dispersed in the matrix and is dissolved totally/partially to form a solid
solution/dispersion in the carrier matrix.

Advantages:

As the dispersion matrix is made from water-soluble sigan, molded tablets degrader rapidly and offer improved taste.
These properties are enhanced when tablets with porous structures are produced or when components that are
physically modified by the molding process are wed la comparison to the lyophilization process, tablets produced by
the molding technique are easier to adapt to the industrial scale

Disadvantage

As the molded tablets have poor mechanical strength, they may undergo passion and braking during handling. Though
hardening can increase the strength of the tablets it would be at the cost of their disintegration time.

Direct Compression (DC):

DC is the simplest and most cost-effective tablet manufacturing technique for MDTs as they can be fabricated using
conventional tablet manufacturing and packaging machinery and also due to the availability of tableting excipients
with improved flow, compressibility, and disintegration properties, especially tables disintegrants, effervescent agents,
and sugar-based excipients

Disintegrants

In many MDT products based on the DC process, the disintegrants mainly affect the rate of disintegration and hence
dissolution which is further enhanced in the presence of water-soluble excipients and effervescent agent

The introduction of super disintegrants has increased the popularity of this technology [31]. Tablet disintegration time
can be optimized by focusing on the disintegrant concentration. Below a critical disintegrant concentration, tablet
disintegration time becomes inversely proportional to 10 disintegrant concentration. However, above the critical
concentration level of disintegrant, disintegration time remains approximately constant or the decrease is insignificant
[32]
Another DC-based technology, Flashtab contains coated crystals of drag and microgranules along with disintegrants
[33]. In this technology, two types of disintegrants are used a disintegrating agent (e.g modified cellulose), which has
a high swelling force, and a swelling agent teg, starch) which has a low swelling force (34)

Bi et al. [35] and Watanabe [36] used microcrystalline cellulose (MCC) and low substituted hydroxypropyl cellulose
(HPC) to manufacture MDTs wherein the ratio of MCC to HPC varied from 8:2 to 9:1. Ito and Sugihara [37]
investigated the application of agar powder as a disintegrant due to its property of absorbing water and considerable
swelling without forming a gel at physiological temperature.

Effervescent Agents:

The evolution of CO2 as a disintegrating mechanism forms the basis of the patented Orasols technology (OT) and is
frequently used to develop over-the-counter formulations [38-40] The product contains microparticles and is slightly
effervescent in nature. Saliva activates the effervescent agent which causes the tablet to disintegrate. The OT had been
utilized in the fabrication of six marketed products: four Triaminic Softchew formulations. Tempra Firs Tabs and
Remeron SolTab.

The present technology uses the concept of effervescence to achieve fast disintegration [41. 42]. In this technology,
the microparticles are prepared by dispersing the drug into a suitable polymer (ethyl cellulose. methylcellulose,
acrylate, or methacrylic acid resins) along with other excipients (mannitol and magnesium oxide). The drug and
mannitol are added to the polymeric dispersion under stirring, followed by the addition of magnesium oxide. Here,
mannitol and magnesium oxide are known as release promoters as they aid in drug release from the polymeric coating.
This mixture is then dried for one hour at 50 °C, dumped, and dried for another hour at the same temperature. The
material is then screened (8-mesh) and dried for one hour at 60 C. The formed microparticles, effervescent agents, and
other excipients are blended and compressed into tablets at 1.0-2.0 kp hardness. The tablets obtained are fragile with
an in-vivo disintegration time of less than one minute (38, 42). As the tablets are very soft, they are packed into
aluminum blisters using a specially designed packaging system. To reduce their friability, a novel method, known as a
particulate effervescent couple, had been developed. In this method, the organic acid crystals are coated using a
stoichiometrically low quantity of base material as compared to acid. The particle size of the organic acid crystals is
carefully chosen to be greater than the base material so that the base gets uniformly coated onto the acid crystals. The
coating process is initiated by the addition of a reaction initiator, which in this case, is purified water. The reaction is
allowed to proceed only to the extent of completion of base coating on organic acid crystals. The required end-point
for the reaction termination is determined by measuring CO2 evolution. The resulting Deffervescent couple can be
used in tablet preparation by mixing with polymer-coated drug particles and other required excipients (39).

Though the Orasolv tablet has the appearance of a traditional compressed tablet, they are lightly compressed and are
weaker and more brittle than conventional tablets. Therefore, special handling and

packaging system for Orasolv was developed [40]. An advantage of a low degree of compaction is that the particle
coating used for taste masking is not compromised by fracture during compression.
Durasolv, a second-generation technology was developed to produce robust MDTs. Durasols have much higher
mechanical strength than their predecessors due to the use of higher compaction pressure during compression. It is
thus produced in a much faster and more cost-effective manner and can be packed in either traditional blister packs or
vials.

The limitations of Durasolv are its low drug loading capacity and high compaction pressure which are not suitable for
the incorporation of taste-masked coated pellets. Therefore, the Durasolv technology is best suited for relatively small
doses of drugs [43]. This technology has been applied in the fabrication of two products Nulev and Zomig ZMT.
However, the major drawback of effervescent excipients is their hygroscopicity which requires control of humidity
during processing and protection of the final product increasing the cost of the product.

Sugar-Based Excipients:

Another approach to manufacturing MDTs by DC is the use of sugar-based excipients (eg, dextrose, fructose, isomalt,
lactitol, maltitol, maltose, mannitol, sorbitol, starch hydrolysate, polydextrose, and xylitol) which display high
aqueous solubility and sweetness and hence, imparts taste masking and a pleasing mouth feel.

Mizumoto et al., [44] have classified sugar-based excipients into two types based on their mouldability and dissolution
rate.

Type I saccharides (e.g., lactose and mannitol) exhibit low mouldability but a high dissolution rate

Type II saccharides (e.g., maltose and maltitol) exhibit high mouldability but a low dissolution rate.

Mouldability is defined as the capacity of the compound to be compressed/molded and to dissolve. It does not refer to
the formation of a true mold by melting or solvent-wetting process. The mouldability of Type 1 saccharide can be
improved by granulating it with a Type II saccharide solution.

The above technology forms the basis of WOWTAB [45] which involves the use of fluidized bed granulation for the
surface treatment of Type I saccharide with Type II saccharide. This technique has been used in the production of
Benadryl Fast melt tablets. Here, two different types of saccharides are combined to obtain a tablet formulation with
adequate hardness and a fast dissolution rate [10]. Due to its significant hardness, the WOWTAB formulation is more
stable under environmental conditions than the Zydis or Orasolv and is suitable for both conventional bottle and
blister packaging. The taste masking technology utilized in the WOWTAB is proprietary and claims to offer a
superior mouthfeel due to the patented smooth-melt action [46]

In the process of granulation, low mouldable sugar was coated with high mouldable sugar followed by a

specific humidity treatment, to achieve fast disintegration. The resulting tablet had a hardness of 1.0-2.0 kg (tablet-
size dependent) and presented a preferable disintegration time of 1-40 secs. Various classes of drugs can be
incorporated into the above sugar combination to achieve an MDT with optimum performance characteristics. A
preferable ratio of 5-10% w/w of high mouldable sugar was found to be sufficient to achieve the desired hardness and
disintegration properties [45]

A series of experiments had been conducted to develop an MDT using a combination of starch/cellulose and one or
more water-soluble saccharides (47). Erythritol was found to be the best saccharide because it displayed rapid
disintegration, good tolerability, sweetening, and a refreshing mouth feel due to its negative heat of solution
Recently, the Ziplet technology was developed, which can be used for water-insoluble drugs or drugs as coated
microparticles. It was found that the addition of a suitable amount of a water-insoluble inorganic excipient combined
with one or more effective disintegrants unparted an excellent physical resistance to the MDT and simultaneously
maintained optimal disintegration even at low compression force and tablet hardness [48]. Breakage of the tablet
edges or formation of powder during manufacturing and opening of the blister pack is avoided because of its superior
mechanical resistance. The use of water-insoluble inorganic excipients also offers better enhancement of
disintegration characteristics in comparison to the most commonly used water-soluble sugars or salts. Ablets
composed primarily of water-soluble components often tend to dissolve rather than disintegrate, resulting in much
longer disintegration. time. As the soluble components dissolve on the tablet's outer layer, a concentrated viscous
solution is formed, which reduces the rate of water diffusion into the tablet core [31].

Cotton Candy Process:

The FLASHDOSE is an MDS manufactured using Shearform technology in association with Ceform TIT™
technology to eliminate the bitter taste of the medicament [49, 50), The Shearform technology is employed in the
preparation of a matrix known as floss", made from a combination of excipients, either alone or with drugs. The floss
is a fibrous material similar to cotton-candy fibers, commonly made of saccharides such as sucrose, dextrose, lactose,
and fructose at temperatures ranging between 180-266 F [51] However, other polysaccharides such as poly
maltodextrins and polydextrose can be transformed into fibers at 30-40% lower temperature than sucrose. This
modification permits the safe incorporation of thermolabile drugs into the formulation [52] The tablets manufactured
by this process are highly porous in nature and offer a very pleasant mouthfeel due to the fast solubilization of sugars
in the presence of saliva. The manufacturing process can be divided into four steps as detailed below.

1)Floss Blend:
In this step, 80% sucrose in combination with mannitol/dextrose and 1% surfactant is blended to form the floss mix.
The surfactant acts as a crystallization enhancer in maintaining the structural integrity of the floss fibers. It also helps
in the conversion of amorphous sugar into a crystalline form from an outer portion of amorphous sugar mass and
subsequently converting the remaining portion of the mass to a complete crystalline structure. This process helps to
retain the dispersed drug in the matrix, thereby minimizing migration out of the mixture [53].

II. Floss Processing The floss formation machine uses flash heat and flash flow processes to produce a matrix from the
carrier material. The machine is similar to that used in cotton-candy" formation which consists of a spinning head and
heating elements. In the flash heat process, the heat induces an internal flow condition of the carrier material. This is
followed by its exit through the spinning head (2000-3600 rpm) that flings the floss under centrifugal force and draws
into long and thin floss fibers, which are usually amorphous in nature [54-56]

III. Floss Chopping and Conditioning This step involves the conversion of fibers into smaller particles in a high-shear
mixer granulator. The conditioning is performed by partial crystallization through an ethanol treatment (1%) which is
sprayed onto the floss and subsequently evaporated to impart improved flow and cohesive properties to the floss [51].

IV. Blending and Compression Finally, the chopped and conditioned floss fibers are blended with the drug along with
other required excipients and compressed into tablets. To improve the mechanical strength of the tablets, a curing step
is also carried out which involves the exposure of the dosage forms to elevated temperature and humidity conditions,
(40 °C and 85% RH for 15 min). This is expected to cause crystallization of the floss material that results in binding
and bridging to improve the structural strength of the dosage form [57].

Spray-Drying:

Allen et al. [58] have used spray drying for the production of MDTs. The formulations contained

hydrolyzed and unhydrolyzed gelatin as a supporting agent for the matrix, mannitol as a bulking agent and

sodium starch glycolate/croscaramellose as a disintegrant. Disintegration and dissolution were further

enhanced by adding an acid (e.g., citric acid) or an alkali (e.g., sodium bicarbonate). The suspension of

above excipients were spray-dried to yield a porous powder which was compressed into tablets. Tablets

manufactured by this method disintegrated in < 20 secs in an aqueous medium.

Sublimation:

Sublimation has been med to produce MDTs with high porosity. A pompous mauris is formed by compressing the
volatile ingredients along with other excipients in tablets, which are finally subjected to a process of sublimation. Inert
solid ingredients with high volatility (eg, ammonian bicarbonate, ammonium carbonate benzoic acid, camphor,
hexamethylene tetramine, naphthalene, phiballc anhydride, urea, and methene) have been used for this purpose [59],
Solvents such as cyclohexane and benzene were also suggested for generating the porosity in the matrix. Makino et al.
[600] reported a method using water as a pore-forming material

Mass-Extrusion This technology Involves softening the active blend using the solvent mixture of water-soluble
polyethylene glycol and methanol and expulsion of softened mass through the extruder or syringe to get a cylindrical
shaped extrude which are finally cut into even segments using a heated blade to form tablets. This process can also be
used to coat granules of bitter drugs to mask their taste (611

Canonization:

A recently developed Nanomeli technology involves a reduction in the particle size of the drug to nanosize by milling
the drug using a proprietary wet-milling technique [62] The nanocrystals of the drug are stabilized against
agglomeration by surface adsorption on selected stabilizers, which are then incorporated into MDTs This technique is
especially advantageous for poorly water-soluble drugs. Other advantages of this technology include fast
disintegration/dissolution of nanoparticles leading to increased absorption and hence higher bioavailability and
reduction in dose, cost-effective manufacturing process, conventional packaging due to exceptional durability, and
wide range of doses (up to 200 mg of drug per unit).

Fast Dissolving Films

It is a new frontier in MDS that provides a very convenient means of taking medications and supplements. In this
technique, a non-aqueous solution is prepared to contain water-soluble film-forming polymer (pullulan,
carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyl ethylcellulose, hydroxyl propyl cellulose,
polyvinyl pyrrolidone, polyvinyl alcohol or sodium alginate, etc.), drug and other taste masking ingredients, which is
allowed to form a film after evaporation of solvent. In the case of a bitter drug, resin adsorbate or coated
microparticles of the drug can be incorporated into the film [63]. This film, when placed in the mouth, melts or
dissolves rapidly, releasing the drug in solution or suspension form. The features of this system include paper-thin
films of size less than 2X2 inches, dissolution in 5 sec, instant drug delivery, and flavored aftertaste [64].

MDTs with Patented Taste Masking Technology:

There are several patented taste masking technologies which had been utilized to maintain MITS with acceptable
taste. CIMA Lahy" taste masking technique involving the coating of drug with dissolution retarding excipient [65],
Microcaps process involving microencapsulation by coacervation-phase separation technique (66, 67). Solutab
technology involving the coating of the drug with a sustained release agent followed by coating with enteric polymer
and finally with mannitol [68] and blending of the drug with cyclodextrins [69] are some of the taste masking
approaches applied in the fabrication of MDTs. One more formulation in this category is the OraQuick formulation
which produces microspheres, known as MicroMask, which has a superior mouthfeel over other taste-masking
alternatives. This process does not involve the use of solvents and therefore, leads to faster and more efficient
production. Moreover, the relatively lower heat of production makes OraQuick appropriate for heat-sensitive drugs.
The matrix that protects the drug in microencapsulated particles is more pliable which enables the tablets to be
compressed with significant mechanical strength without disrupting the taste-masking property. Along with good
taste-masking ability. OraQuick also claims quick dissolution (in secs) of the MDT [70]. This technology has also
been utilized in the development of MDTs containing Hyoscyamine sulfate, which is a bitter-tasting
anticholinergic/antispasmodic drug (71) AdvaTab technology utilizes a combination of Microcaps technology for taste
masking and Diffuscap controlled release technology for the development of a highly differentiated controlled release
MDT product [72]

FUTURE SCOPE:
Although there are a large number of commercial products on the market, there are still many
aspects to improve in the MDT formulations.MDT technologies are now a day’s very advanced, but the formulation of
hydrophobic drugs is still a challenge, especially when the amount of drug is high. A new technology is being
developed to incorporate higher doses of
hydrophobic drugs without affecting the fast disintegrating property. In the future, scientists also
be involved in the development of MDTs with controlled release properties. If one MDT can
deliver drugs with short half-lives for 12–24 hours, it would be a quantum improvement in the MDT technology. The
added convenience and compliance of such formulations would be
enormous. In the future, new technologies invented to develop effective taste-masking properties. The use of the
coating in case of poorly-tasting drugs is commonly used,
but it increases the total volume of the final formulation. So, with continued innovations, one
can expect the emergence of more novel technologies for MDTs in the days to come. Several companies have their
brands of fast-dissolving tablets. The use of
modern technologies and the advantages of fast-dissolving tablets will increase their popularity shortly and it is
expected that a day may come when these fast-dissolving tablets due to their remarkable advantages may replace a
large percentage of conventional products

CONCLUSION: -

Quick dispersing oral drug delivery systems are defined as oral drug delivery systems that when placed in the mouth
dissolve or disintegrate within a few seconds to a few minutes and do not require water to aid swallowing. The FDT
dosage forms are ideal for many groups of patients including geriatrics, pediatrics, and those people who have
difficulty swallowing. An important benefit of FDT dosage forms is the ability to provide the advantages of a liquid
medication in the form of a solid preparation. This feature enables the patient to take the dose as directed at any time
without water and inconvenience. There is a clear medical need and clinical benefits provided by these technologies
and products.

References:

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ERRATA

ERRATA

Sr. No.ContentPage No.

1Introduction1
2Aim and objective2
3Literature review3
4Future scope22
5Conclusion23
6Reference24
7Errata26

CHAPTER NOLINE NO.MISTAKESCORRECTIONREMARK

DR.N.J. PAULBUDHE COLLEGE OF PHARMACY AHMEDNAGAR