INTRODUCTION:
Many
pharmaceutical dosages form are administered in the form of pills, granules,
powder and liquid for conventional use. However, some patients, particularly
pediatrics and geriatric patients, have difficulty in swallowing or chewing
solid dosage forms. Many pediatrics and geriatric patients are unwilling to
take these solid preparations due to a fear of bitter taste. In order to assist
these patients, several mouth dissolving drug delivery systems have been
developed.[1]
Their
growing importance was underlined recently when European pharmacopoeia adopted
the term “Orodispersible tablet” as a tablet that to be placed in the mouth
where it disperses rapidly before swallowing.[2]
According
to European pharmacopoeia, the ODT should disperse/ disintegrate in less than
three minutes. The basic approach in development of FDT is the use of super
disintegrants like cross linked carboxymethyl cellulose (croscarmellose),sodium
starch glycolate (primogel, explotab), polyvinylpyrollidone (polyplasdone) etc,
which provide instantaneous disintegration of tablet after putting on tongue,
their by release the drug in saliva. The bioavailability of some drugs may be
increased due to absorption of drug in oral cavity and also due to pre-gastric
absorption of saliva containing dispersed drugs that pass down into the
stomach. More ever, the amount of drug that is subjected to first pass
metabolism is reduced as compared to standard tablet. The technologies used for
manufacturing fast dissolving tablets are freeze-drying, spray-drying, tablet
molding, sublimation, sugar-based excipients, tablet compression, and
disintegration addition. As a result of increased life expectancy, the elderly
constitute a large portion of the worldwide population today. These people
eventually will experience deterioration of their physiological and physical
abilities.[3]
STRUCTURE OF ABSORPTION SITE:
The mucosa in the buccal cavity consist of
non-keratinized structure with a thickness about 100-200 micrometer. Its normal
turn over time is 20 days. It has a surface area of about 26.5 square cm.
Around 12.2 ml of blood flows in 100 gm of tissue per minute here. The average
residence time of substances taken in oral cavity is poor but the permeability
is very good due its high amount of blood supply. [6, 7]
ADVANTAGES[8, 9]
·
Administration to the
patients who cannot swallow, such as the elderly, bed ridden patients, patients
affected by renal failure and patients who refuse to swallow such as pediatric,
geriatric and psychiatric patients.
·
Rapid drug therapy
intervention.
·
Achieve increased
bioavailability/rapid absorption through pre-gastric absorption of drugs from
mouth, pharynx and esophagus as saliva passes down.
·
Convenient for
administration and patient compliant for disabled, bedridden patients and for
travelers and busy people, who do not always have access to water.
·
Good mouth feel property
helps to change the perception of medication as bitter pill particularly in
pediatric patients.
·
The risk of chocking or
suffocation during oral administration of conventional formulations due to
physical obstruction isavoided, thus providing improved safety.
·
New business opportunity
like product differentiation.
DISADVANTAGES[10, 11]
·
Hygroscopic in nature.
·
Low amount of drug can be incorporated in each dose.
·
Some time it possesses mouth feeling
·
Highly fragile sometimes.
·
Requires special packaging for properly stabilization and safety
of stable product.
·
Eating and drinking may become restricted
CHALLENGES
IN FORMULATION OF ORODISPERSIBLE TABLETS[7, 8]
1.
Disintegration time and mechanical
strength:
ODTs are formulated to obtain
disintegration time usually less than a minute. While doing so, maintaining a
good mechanical strength is a prime challenge. Many ODTs are fragile and there
are chances that such fragile tablet will break during packing, transport or
handling by the patients. Tablets based on technologies like Zydis need special
type of packaging. It is very natural that increasing the mechanical strength
will delay the disintegration time. So a good compromise between these two
parameters is always essential.
2.
Taste masking:
Many drugs are bitter in taste. A tablet
of bitter drug dissolving/ disintegration in mouth will seriously affect
patient compliance and acceptance for the dosage form. So effective taste
masking of the bitter drugs must be done so that the taste of the drug is not
felt in the oral cavity. Number of techniques are developed for masking the bitter
taste of most of the drugs, that includes formation of pellets by extrusion,
spheronization or mass extrusion, coating of drug using a taste masking
polymer, spray drying the drug dispersed in a polymeric solution, complexation
of drug by inclusion in cyclodextrin,
drug-resinate complex formation, microencapsulation of drug by polymer.
3.
Sensitivity to environmental
conditions:
ODTs generally should exhibit low
sensitivity to environment conditions such as humidity and temperature as most
of the materials used in ODTs are meant to dissolve in minimum quantity of
water.
4.
Mouth feel:
ODTs should not disintegrate into larger
particles in the oral cavity. The particles generated after disintegration of
the ODTs should be as small as possible. ODTs should leave minimal or no
residue in mouth after oral administration. Moreover addition of flavors and
cooling agents like menthol improve the mouth feel.
5.
Cost:
The technology used for ODTs should be
acceptable in terms of cost of the final product. Methods like Zydis and
Orasolv that require special technologies and specific packaging increase the
cost to a remarkable extent.
TECHNIQUES
USED IN PREPARARTION OF ODTs[12, 13]
1.
Freeze drying/ Lyophilization:
Lyophilization means drying at low
temperature under condition that involves the removal of water by sublimation.
Drug in a water soluble matrix which is then freeze dried to give highly porous
structure. The tablets prepared by lyophilization disintegrate rapidly in less
than 5 seconds due to quick penetration of saliva in pores when placed in the
oral cavity. Lyophilization is useful for heat sensitive drugs i.e.
thermo-labile substances. Freeze drying process normally consists of three
steps: Material is frozen to bring it below the eutectic point. Primary drying
to reduce the moisture around 4% w/w of dry product. Secondary drying to reduce
the bound moisture up to required final volume.
Advantages: More rapid dissolution than
other available solid products.
Disadvantages: High cost of the equipments and
lack of physical resistance in blister packs.
2.
Spray drying:
This technique is based on a particulate
support matrix, which is prepared by spray drying an aqueous composition
containing support matrix and other components to form a highly porous and fine
powder. This then mixed with active ingredients and compressed into tablets.
The formulations are incorporated by hydrolyzed and non hydrolyzed gelatins as
supporting agents, mannitol as bulking agent, sodium starch glycolate or
croscarmellose sodium as disintegrating and an acidic material (e.g. citric
acid) and / or alkali material (e.g. sodium bicarbonate) to enhance
disintegration and dissolution. Tablet compressed from the spray dried powder
disintegrated within 20 seconds when immersed in an aqueous medium.
Advantages: Rapid disintegration of
tablets.
3.
Molding:
Tablets prepared by this method are solid
dispersions. Molded tablets offer improved taste due to water soluble sugars
present in dispersion matrix. Molding process is of two type’s i.e. solvent
method and heat method. Solvent method involves moistening the powder blend
with a hydro alcoholic solvent followed by compression at low pressures in
molded plates to form a wetted mass (compression molding). The solvent is then
removed by air-drying. The tablets manufactured in this manner are less compact
than compressed tablets and posses a porous structure that hastens dissolution.
The heat molding process involves preparation of a suspension that contains a
drug, agar and sugar (e.g. mannitol or lactose) and pouring the suspension in
the blister packaging wells, solidifying the agar at the room temperature to
form a jelly and drying at 30○C under vacuum.
Advantages: Molded tablets disintegrate
more rapidly and offer improved taste because the dispersion matrix is, in
general made from water soluble sugars.
Disadvantages: Molded tablets do not possess
great mechanical strength. Erosion and breakage occur during handling and
opening of blister packages.
4.
Sublimation:
In this method a subliming material like
(Ammonium bicarbonate, Ammonium carbonate, Urea, Benzoic acid, Naphthalene,
camphor) is removed by sublimation from compressed tablets and high porosity is
achieved due to the formation of many pores. Where camphor particles previously
existed in the compressed tablets prior to sublimation of the camphor. A high
porosity was achieved due to the formation of many pores where camphor particles
previously existed in the compressed mannitol tablets prior to sublimation of
the camphor. These compressed tablets which have high porosity (approximately
30%) rapidly dissolved within 15seconds in saliva.
Advantage: Tablets dissolve in 10-20 sec. and exhibit
sufficient mechanical strength.
5.
Mass Extrusion:
This technology involves softening of 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
heated blade to form tablets. This process can also be used to coat granules of
bitter drugs to mask their taste.
Advantage: Mask bitter taste by coating the granules.
6.
Direct Compression:
Direct compression represents the simplest
and most cost effective tablet manufacturing technique. This technique can now
be applied to:
a)
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. For the success of fast
dissolving tablet, the tablet having quick dissolving property which is
achieved by using the super disintegrants.
Types
of superdisintegrants[14]
(i).
Natural
(ii).
Synthetic
1. Natural
These
are various plant based material. Plant based material serve as an alternative
to synthetic products because of following reasons;
·
Local accessibility
·
Eco-friendly
·
Bio-acceptable
·
Renewable source and low price as compared to synthetic products
Example: Lepidus sativum, Locust bean gum, Isapghula Husk (Plantago ovata), Hibiscus rosa sinesis linn. Mucilage etc.
2. Synthetic
Advantages of synthetic
superdisintegrants:
·
Effective in lower concentrations than starch.
·
Less effect on compressibility and flow ability.
·
More effective intra-granularly.
MECHANISMS
OF SUPERDISINTEGRANTS:
Mechanism of disintegration
There
are four major mechanisms for tablet disintegration as follows [19]
1)
Swelling:
Although not all effective disintegrants
swell in contact with water, swelling is believed to be a mechanism in which
certain disintegrating agents (such as starch) impart thedisintegrating effect.
By swelling in contact with water, the adhesiveness of other ingredients in a
tablet is overcome causing the tablet to fall apart.
Mechanism of
superdisintegrants by swelling
2) Porosity and capillary action (wicking):
Tablet
in the aq. Media leads to penetration of the medium into tablet and thus
replacement of air adsorbed resulting in weakening of intermolecular bond and
breaking of tablet into fine particles.
Mechanism of
superdisintegrants by Porosity and capillary action (wicking).
3) Due to particle-particle repulsive forces:
The
electric repulsive forces b/w particles responsible for disintegration. It is
secondary to wicking.
Mechanism of
superdisintegrants due to particle-particle repulsive forces
4) Due to deformation:
During
tab. compression, disintegrated particles gets deformed and in contact with aq.
media returns to normal structure (inc. in size).E.g.: starch.
Mechanism of
superdisintegrant due to deformation.
b)
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 mouth feel.
Advantages: It is cost effective due to
low manufacturing cost, conventional equipments and limited number of processing
steps.
Disadvantages: Differences in particle size and bulk
density b/w the drug and diluents may lead to stratification within the
granulation. Large dose may present problem if it is not easily compressible by
itself.
7.
Phase transition process:
FDT were produced by compressing powder
containing erythritol (melting point: 122 °C) and xylitol (melting point:93 95
°C), and then heating at about 93 °C for 15 min. After heating, the median pore
size of the tablets was increased and tablet hardness was also increased. The increase
of tablet hardness with heating and storage did not depend on the crystal state
of the lower melting point sugar alcohol.
8.
Cotton Candy Process:
This process utilizes a unique spinning
mechanism to produce floss-like crystalline structure. 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 improve flow property and compressibility. This candy floss
matrix is then milled and blended with active ingredients and excipients and subsequently
compressed to orally disintegrating tablet. This process can accommodate larger
drug doses and offers improved mechanical strength. However, high-process temperature
limits the use of this process.
9.
Nanonization:
A recently developed Nanomelt technology
involves reduction in the particle size of drug to nanosize by milling the drug
using a proprietary wet-milling technique. The nanocrystals of the drug are
stabilized against agglomeration by surface adsorption on selected stabilizers,
which are then incorporated into ODTs. This technique is especially
advantageous for poor 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).
IMPORTANT
PATENTED TECHNOLOGIES IN ODTs[20-23]
1.
Zydis:
ZYDIS® (R.P. Scherer, Swindon, UK), using
freeze drying processes, is one of the first generations of fast disintegrating
dosage forms. There are approximately 12marketed ZYDIS® products, including
lorazepam, piroxicam, loperamide, loratidine, enalapril .This drug delivery
system consists of freeze-dried tablet shaving active drug designed to rapidly
disintegrate in the mouth. The freeze-dried tablet is made by lyophilizing a
suspension or solution of drug containing various excipients such as polymer, polysaccharides,
preservatives, pH adjusters, flavors, sweeteners, and colors, which is then
filled in blisters. Freeze drying occurs in the blisters, which are then sealed
and further packaged. Some of the advantages of the Zydis system include fast
disintegration time. Some of the disadvantages include low throughput, high
cost of goods, and limited taste masking.
2.
OraSolv, DuraSolv, and PakSolv:
OraSolv and DuraSolv are CIMA’s core ODT
tablet based technologies. The ingredients contained in the technology include
polyols as fillers, disintegrant, which may include an effervescence couple,
flavor, sweetener, and lubricant. The drug may be taste masked if required
typically utilizing a fluid bed coating process. The tabletting process
includes direct compression, and can accommodate a wide range of potency from
less than 1 mg to as high as 500 mg. Tablets manufactured with OraSolv
technology should contain an effervescence couple along with microparticles of
drug within a rupturable coat. The tablets manufactured are compressed at a low
hardness that promotes fast disintegration. The dosage forms need to be packaged
in foil–foil aluminum blisters with a dome shape that impact physical
protection and impermeability to moisture. This constitutes the PakSolv
Technology. PakSolv is a “dome shaped” blister package that prevents the
vertical movement of the tablet within the depressions, because the diameter of
the lower portion of the dome is too narrow to accommodate the tablet. PakSolv
also offers light, moisture, and child resistance. Tablets manufactured with
DuraSolv technology contain a non-directly compressible filler and a lubricant.
They may or may not contain effervescence, and the drug need not be taste
masked. DuraSolv tablets are compressed at higher hardness compared to OraSolv
that allows for packaging in bottles or push through blisters.
Advantage: low cost of goods, standard
manufacturing technology, standard packaging format and materials, and low development
costs and risks.
Disadvantage: slightly longer disintegration
time.
3.
Lyoc:
Lyoc technology is owned by Cephalon
Corporation. CIMA is a subsidiary of Cephalon, and currently manages the Lyoc R
and D effort ts. This was the first freeze-drying based technology introduced
for ODTs. The process involves preparation of a liquid solution or suspension
of the drug containing fillers, thickening agents, surfactants, non-volatile flavoring
agents, and sweeteners. This homogenous liquid is then deposited in blister
cavities and subjected to freezedrying.
Advantage: compared to other freeze dried
dosage forms include absence of preservatives.
4.
Flashtab:
Flashtab tablet matrix consists of a
swellable agent (modified starch or microcrystalline cellulose) and a super
disintegrant (crospovidone or croscarmellose). The system may also contain,
depending on the need, a highly water-soluble polyol with binding properties
such as mannitol, sorbitol, maltitol, or xylitol, instead of the swellable agent
as mentioned before. The active is taste masked by direct coating. Tablets
manufactured using this technology produce durable tablets in which the
excipients are first granulated using wet or dry granulation process, then the coated
drug is mixed with the excipients granules and compressed into tablets that can
be handled and packaged using conventional processing equipment. Tablets for
blister packaging can withstand the pressure used to push the tablet out of the
lidding foil of the blister card. Tablets containing hygroscopic material can
also be blister packaged, by using high-quality polyvinyl chloride or aluminum
foils, which provide a higher degree of moisture protection than ordinary
polyvinyl chloride or polypropylene foils.
5.
Flash Dose:
Fuisz technologies were the inventor of
the Flash Dose technology. It is now owned by Biovail. FlashDose tablets are
manufactured utilizing SHEARFORM matrix in which material containing
substantial amounts of fibrous polysaccharides, which are processed by
simultaneous action of flash melting and centrifugal force, are compressed to form
fine sugar fibers. FlashDose tablets containing a matrix of these sugar fibers
disintegrate very rapidly upon contact with saliva, with disintegration times
of a few seconds. The tablets produced by FlashDose are hydrophilic and highly porous,
owing to relatively low compression during the pressing of the tablets. For
taste masking, Fuisz uses its own patented, single-step, solvent-free process,
termed ‘‘CEFORMTM technology,’’ which produces uniform microspheres with a very
narrow particle size distribution. The resulting tablets produced by this
process are soft, friable, and highly moisture sensitive. They require specialized
packaging materials and processes to protect them from external humidity and
mechanical abrasion.
6.
Wow tab:
Wow tab technology is patented by Yamanouchi
Pharmaceutical Co. WOW means “Without Water”. In this process, combination of
low mouldability saccharides with hardness 0-2 kg and high mouldability saccharides
with hardness more than 2 kg is used to obtain a rapidly melting strong tablet.
The active ingredient is mixed with a low mouldability saccharide e.g. lactose,
glucose, and mannitol and granulated with a high mouldability saccharide e.g.
Maltose, Oligosaccharides and compressed into tablet.
7.
Pharmaburst technology:
Pharmaburst™ is a “QuickDissolve” delivery
system patented by SPI Pharma. Pharmaburst is a co-processed excipient system
which involves a dry blend of a drug, flavors, and lubricant then followed by
compression into tablets which then dissolve within 30-40 seconds. Tablets
manufactured by this methodology have sufficient strength can be packed in blister
packs and bottles.
8.
FrostaTM:
Akina owns Frosta technology. The
technology incorporates manufacture of highly plastic granules using aplastic
material, a material enhancing water penetration, and a wet binder. These
granules can then be compressed into tablets at low pressure, thus enabling
fast disintegration upon administration. The tablets obtained have excellent hardness
and rapid disintegration time ranging from 15 to30 sec depending on size of
tablet.
9.
Quicksolv technology:
Quicksolv (Janssen Pharmaceutica, Beese,
Belgium). In the Quicksolv formulation, the matrix compositions are dissolved
in the solvent (usually water), and then this solution is frozen. At the
temperature the first solvent will remain in the solid form, and then the
frozen solution contacts the second solvent which is usually, ethanol, menthol,
or acetone. Thus, the first solvent is removed after a few hours of contacting
the second solvent to result in a usable matrix. The final product
disintegrates almost instantly. This method is claimed to prevent or to reduce
the incidence of cracking during the final preparation, having uniform porosity
and also the adequate strength for handling.
10.
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 drugs. As
manufacturing losses are negligible, this process is useful for small
quantities of drug.
11.
Ziplets/advatab:
This technology is patented by Pessano con
Bornago, 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.
PRE-COMPRESSION
PARAMETERS[24, 25]
1. Bulk Density:
Apparent
bulk density was determine by pouring the 5 gram of powder into a 100 ml granulated
cylinder. The bulk volume (V)poured drug was determined. The bulk density was
calculated using the formula.
ρb = M / V
Where: ρb - bulk density.
M- Weight of powder.
V- Volume of powder.
2.
Tapped Density:
Weight
5 g. of powder and placed in a measuring cylinder. Measuring cylinder containing
known mass (5 gm) of powder was tapped for 100 times or fixed time. The minimum
volume (Vt) occupied was measured. The tapped density was calculated using
following formula.
ρt = M / Vt
3. Compressibility Index:
The
simplest way for measurement of free flow of powder is compressibility, an indication
of the ease with which a material can be induced to flow is given by Compressibility
Index. The value below 15%indicates a powder with give rice to good flow
properties, whereas above 25% indicate poor flow ability. Which is calculated
follows.
% C.I. = ρt – ρb/ ρt × 100
4. Hausner ratio:
Hausner
ratio is an indirect index of ease of powder flow. Hausner ratio is the ratio
of tapped density to bulk density. Lower the value of Hausner ratio better is
the flow property. Powder with Hausner ratio less than1.18, 1.19, 1.25, 1.3-
1.5 and greater the 1.5indicate excellent, good, passable, and very poor,
respectively. It is calculated by following formula.
Hausner
ratio = ρt/
ρb
5. Voide Volume:
Voide
volume (V) was obtained by difference between bulk volume (Vb) and tapped
volume(Vp).Voide volume can be calculated by following formula-
V = Vb – Vp
6. Angle of repose:
The
angle of repose was determined using funnel method. Funnel that can be fit vertically
with stand at 6.3 cm. height. The opening end of funnel is closed with thumb until
drug is poured. The 5 gm of powder was poured into funnel that can be raised vertically
until a maximum cone height (h) was obtained. Radius of the heap (r) was
measured and the angle of repose (θ) was calculated using the formula.
θ = Tan-1 (h / r)
EVALUATION[26-29]
1. Uniformity of weight:
I.P.
procedure for uniformity of weight was followed, twenty tablets were taken and
their weight was determined individually and collectively on a digital weighing
balance. The average weight of one tablet was determined from the collective
weight. The weight variation test would be a satisfactory method of determining
the drug content uniformity.
2. Thickness:
Tablet
thickness can be measured using a simple procedure. 5 tablets were taken and their
thickness was measured using Varnier calipers.
3. Hardness:
It
is the force required to break a tablet by compression in the radial direction,
it is an important parameter in formulation of ODTs because excessive crushing
strength significantly reduces the disintegration time. In the present study
the crushing strength of the tablet was measured using Pfizer hardness testers.
An average of three observations is reported.
4.
Disintegration time:
The
test was carried out on 6 tablets using the apparatus specified in I.P.-1996
distilled water at 37ºC±2ºC was used as a disintegration media and the time in
second taken for complete disintegration of the tablet with no palatable mass
remaining in the apparatus was measured in seconds.
5.
Taste/ Mouth sensation:
Mouth-feel is critical, and patients
should receive a product that feels pleasant. One tablet from each batch is
tested for the sensation by placing the tablet on the tongue. The healthy human
volunteers are used for evaluation of mouth feel. Taste evaluation is done by a
panel of 5 members using time intensity method. Sample equivalent to 40 mg i.e.
dose of drug is put in mouth for 10 seconds and record taste instantly and then
after 10 sec, 1, 2, 4 and 6 minutes. Volunteer’s opinion for the taste is rated
by giving different score values i.e. 0 = good, 1 = tasteless, 2 = slightly
bitter,3 = bitter, 4 = awful.
6. In-vitro drug release:
The
development of dissolution methods for ODTs is comparable to the approach taken
for conventional tablets, and is practically identical. Dissolution conditions
for drugs listed in a pharmacopoeia monograph, is a good place to start with
scouting runs for a bioequivalent ODT. Other media such as 0.1NHCl and buffers
(pH - 4.5 and 6.8) should be evaluated for ODT much in the same way as their
ordinary tablet counter parts. The USP 2 Paddle apparatus is used for this purpose
which is the most suitable and common choice for orally-disintegrating tablets,
with a paddle speed of 50 rpm commonly used. Typically the dissolution of ODT
is very fast when using USP monograph conditions; hence slower paddle speeds
maybe utilized to obtain a profile. The USP 1Basket apparatus may have certain applications
but sometimes tablet fragments or disintegrated tablet masses may become trapped
on the inside top of the basket at the spindle where little or no effective
stirring occurs, yielding irreproducible dissolution profiles.
7. Friability test:
Friability
of the tablets was determined using Roche friability (Electro lab, Mumbai).
This device subjects the tablets to the combined effect of abrasions and shock
in a plastic chamber revolving at 25 rpm and dropping the tablets at a height
of 6 inches in each revolution. Pre-weighed sample of tablets was placed in the
friabilator and were subjected to100 revolutions. Tablets were de dusted using a
soft muslin cloth and reweighed. The friability (f) is given by the formula.
f = (1- W0 / W) × 100
Where, W0 is weight of the tablets before the test
and W is the weight of the tablet after the test.
8. In-vitro dispersion time test:
To
determine dispersion time 10 ml measuring cylinder was taken in which 6 ml distilled
water was added and tablet was dropped in it. Time required for complete dispersion
was determined.
9. Wetting time:
Five
circular tissue papers of 10 cm diameter are placed in a petridish with a 10 cm
diameter. Ten millimeters of water-containing Eosin, a water-soluble dye, is
added to petridish. A tablet is carefully placed on the surface of the tissue
paper. The time required for water to reach upper surface of the tablet is
noted as a wetting time.
10. Water absorption ratio:
A
piece of tissue paper folded twice was placed in a small Petri dish containing
6 ml of water. A tablet was put on the paper and the time required for complete
wetting was measured. The wetted tablet was then weighed. Water absorption
ratio (R), was determined using following equation,
R = 10 (Wa /Wb)
Where- Wb is weight of tablet before water absorption
and Wa is weight of tablet after water absorption.
11. Accelerated Stability study:
The
Orally disintegrating tablets are packed in suitable packaging and stored under
the following conditions for a period as prescribed by ICH guidelines for
accelerated studies.
(i) 40 ± 1 °C
(ii) 50 ± 1°c
(iii) 37 ±1 ° C and
Relative Humidity= 75% ± 5%
The tablets were withdrawn after a period of15 days
and analyzed for physical characterization (Visual defects, Hardness, Friability,
Disintegrations, and Dissolution etc.) and drug content. The data obtained is fitted
into first order equations to determine the kinetics of degradation.
Accelerated stability data are plotting according Arrhenius equation to
determine the shelf life at 25 ° C.
12. Packaging:
Packaging
special care is required during manufacturing and storage to protect the dosage
of other fast-dissolving dosage forms. Quick-dispersing and/or dissolving oral delivery
systems, the system can be packaged using various options, such as single
pouch, blister card with multiple units, multiple unit dispenser, and
continuous roll dispenser, depending on the application and marketing objectives.
CONCLUSION:
The
popularity of MDTs has increased tremendously over the last decade because of
better patient acceptance and compliance and may offer improved
biopharmaceutical properties, For example, they require smaller amounts of
active ingredient to be effective, improve absorption profiles, and offer
better drug bioavailability than conventional tablets and capsules. Today, fast disintegrating tablets are more widely available as
over-the-counter products for the treatment of allergies, cold and flu
symptoms. ODTs are
to maximize the porous structure of the tablet matrix and incorporate super
disintegrating agents in optimum concentration so as to achieve rapid
disintegration and instantaneous dissolution of the tablet along with good
taste masking properties and excellent mechanical strength.
REFERENCE:
1.
S Dali,
C Subhashis , S Sanjay and M Brahmeshwar. Mouth Dissolving Tablets I: An
Overview of Formulation Technology. International
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