Melt In Mouth
Tablet: A Review
P. Wadhwani College of Pharmacy, Yavatmal,
MS India
ABSTRACT
Oral solid dosage form are more popular than other
dosage form but suffer from problems like taste, solubility, bioavailability;
so patient compliance.
To improve patient compliance, melt in mouth tablets
have emerged as an alternative to conventional oral dosage form. The aim is to
provide the tablet that quickly melts upon contact with saliva and also
provides a good mouthfeel.
INTRODUCTION
They
are solid dosage forms that dissolve or disintegrate within a minute in the
oral cavity without the need of water or chewing and have a pleasant taste.
They are popularly known as orally disintegrating tablets (ODT) and also called
fast-dissolving, fast-melting or fast-disintegrating. The CDER, FDA defines an
ODT to be solid dosage form containing medicinal substance(s), which
disintegrates rapidly, usually within a matter of seconds, when placed upon the
tongue. The European Pharmacopoeia recognizes the MMTs as orodispersible
tablets or tablets intended to be placed in the mouth that subsequently
disperses rapidly before being swallowed. Various terminologies with their
acronyms are being used to describe an MMT by various drug delivery researchers
and inventor companies. These are: melt in mouth/ (mouth melt) tablet (MMT);
fast-melting tablet (FMT); fast-dissolving/ disintegrating tablet (FDT); orally
disintegrating tablet (ODT); mouth dissolve tablet (MDT); rapidly
disintegrating tablet (RDT); and orodispersible tablet(OT).
The
venture's latest technology, called Frosta™, involves
tablet formulations that can melt in a patient's mouth as quickly as 10 seconds
– much faster than existing commercial products made by tablet press machines.
The fast-melting nature of the tablets resembles the melting of frost, hence
the name Frosta™.1
To
fulfil all these needs the concept of melt in mouth
or orodispersible tablet is developed, tablet that disintegrate in saliva,
without need of drinking water within 15 to 60 seconds which offers fast
absorption and then onset of action.2
Ideal
characteristics of melt in mouth tablets:2
1]
They should not require water for administration yet dissolve or disintegrate
in the mouth within a few seconds.
2]
They should have pleasing mouthfeel.
3]
They should allow high drug loading.
4]
They should leave minimal or no recidue.
5]
They should be compatible with taste masking.
6]
They should be portable without fragility concerns.
7]
They should exhibit low sensitivity to environmental conditions such as humidity
and temperature.
8]
Conventional processing packaging equipment at low cost.
2]
ADVANTAGES OF MELT IN MOUTH TABLET:3
1]
Ease of administration to paediatric and geriatric patients and psychiatric
patients.
2]
Bioavailability of drug is increased..
3]
No need of water, convenient for traveler.
4]
Good mouth feel changes particularly for paediatric.
5]
Produce rapid onset of action.
6]
Convenience of administration and accurate dosing as compared to liquids.
7]
Ability to provide advantages of liquid medication in the form of solid
preparation.
8]
Free of the risk of suffocation due to physical obstruction when swallowed,thus offering improved safty.
9]
New business opportunities: line extension,exclusivity
of product promotion,and patent life extention
Fig. 1- Formulated tablet dissolving
Significance
Of The Fast Dissolving/Disintegrating Drug Delivery System.4
CLINICAL:
Ø Improved
drug absorption.
Ø Faster
onset of action.
Ø Minimized
first pass effect.
Ø Improved
Bioavailability.
MEDICAL:
Ø No
tablet or capsule to swallow or chew.
Ø Better
taste, no water needed.
Ø Improved
safety and efficacy.
Ø Improved
compliance.
Ø Good
mouth feels property.
Ø Advantages
of liquid medication in solid preparation.
Ø More
accurate dosing than liquid products.
Ø Improved
stability because of unit-dose packaging.
Ø Manufactured
with common process and conventional equipment
Ø Advantages
of liquid medication in solid preparation.
Technique
for preparing fast dissolving tablet
|
METHODS |
BASIC APPROACH |
|
Freeze-drying Moulding Sublimation Spray-Drying Mass-Extrusion Direct Compression |
Lyophilisation imparts glossy amorphous stru. Microparticles dispersed in matrix . Porous structure High porous,fine pow. Softening active blend Disintegrants,
water-soluble excipientsand effervescent agent. |
TECHNIQUE FOR PREPARING FAST
DISSOLVING/DISINTEGRATING:
TABLETS3
Following
are the various methods developed for designing of melt in mouth tablets.
1) Freeze Drying (Zydis
Method):5-8
Freeze-drying
or lyophillazation can be utilized to prepare
mouth-dissolving tablets, which are very porous in nature and which quickly
disintegrate or dissolve upon contact with saliva. This method involves
incorporation of the drug in water-soluble matrix, which is then transferred to
the preformed blister with peel able foil, as the Zydis
units are not strong enough to withstand being pushed through the lidding foil of a conventional blister, Freeze drying is
then done to remove water by sublimation13.
R.P.
Scherer patented Zydis technology by employing freeze
drying process for the preparation of mouth dissolving tablet on the basis of
patent issued to Gregory et al14-15. Seager
discussed formation, process technology and Bioavailability of fast dissolving
tablets prepared by Zydis technology. The major
disadvantage associated with freeze-dried fast dissolving tablets is fragility,
which creates difficulty in conventional packaging and posses stability problems
during storage. However in order to improve stability problems, Blank et al.,
used a mixture of mannitol and natural gum as carrier
material in formulation of freeze dried tablets and concluded that the tablets
showed improved stability in blister pack even when they were stored in
stressful conditions16.
2)
Moulding:
Moulded
tablets are prepared by using water-soluble ingredients so that the tablet
dissolve or disintegrate rapidly and completely29. Powder is
moistened with the help of hydro alcoholic solvent and then moulded
into tablets under pressure less than the conventional dosage form. The
solvents are removed by air-drying. The tablet possesses porous structure,
which facilitates easy dissolution. Adding sucrose, acacia or PVP.30, 22, may increase
the mechanical strength of the tablet.
3)
Sublimation:9-13
The basic principle involved in preparing fast dissolving tablets by sublimation technique is addition of a volatile salt to the tabletting components, mixing the components to obtain a substantially homogeneous mixture and volatizing a volatile salt. The removal of volatile salts creates pores in the tablet, which help in achieving rapid disintegration when the tablet comes in contact with saliva. Camphor, Naphthalene, Urea, ammonium bicarbonate, etc, can be used to prepare porous tablets of good mechanical strength. Koizumi et.al.used mannitol as diluent and camphor as a volatile material to prepare porous compressed tablets. The tablets were subjected to vacuum at 800C for 30 min to eliminate the camphor and thus forms the pores in the tablet. Makino et.al. Utilized water as a pore forming material in order to prepare porous tablets with excellent mechanical strength and dissolution character. The major steps involved in the sublimation technique are shown in following figure.
4)
Spray Drying:14-19
Spray
Drying can be used to prepare rapidly dissolving tablet. This technique is
based upon a particulate support matrix that is prepared by spray drying and
aqueous composition containing support matrix and other components to form a
highly porous and fine powder. This is then mixed with active ingredient and
compressed into tablet. The fast dissolving tablet prepared from spray drying
technique disintegrated within 20 seconds.
5)
Disintegrant addition (Direct compression):20-23,2
Disintegrant
addition technique is one of the popular techniques for formulating mouth
dissolving tablets because of its easy implementation and cost effectiveness.
The basic principle involved in formulating mouth-dissolving tablets by disintegrant addition technique is addition of superdisintegrant in optimum concentration so as to achieve
rapid disintegration along with good mouth feel. The incorporation of
microcrystalline cellulose and low substituted hydroxy
propyl cellulose in the ratio of 8:2 to 9:1 gives
shortest disintegration time. Fast dissolving tablet having analgesic activity
was formulated using a combination of different superdisintegrant.
Fast dissolving tablet of efavirenz (anti HIV agent)
were formulated by using combination of microcrystalline cellulose and sodium
starch glycolate as superdisintegrant
Disintegrants
can help to facilitate drug dissolution and consequently can improve
bioavailability. Despite a long and proven record of starch, as a disintegrant, it posses a disadvantages when used in direct
compression formulation. The relatively high levels required and the lack of
compressibility often weakens the tablet structure. Therefore the development
of new disintegrants that are effective at lower
concentrations and help in rapid disintegration is of great importance in
formulations for direct compression. A number of disintegrants,
known as superdisintegrant like cross-linked carboxymethyl cellulose (Ac-di-sol®),
Sodium starch glycolate (Explotab®)
and crospovidone (polyplasdone
XL®) markedly improve the tablet disintegration by swelling and exerting
sufficient pressure in the tablet to break it apart into small segments. These superdisintegrants have a high swelling index at lower
concentrations. So they are used in the formulation of fast
dissolving/disintegrating tablets.
Disintegrants, an important excipient
of, the tablet formulation are always added to tablet to induce breakup of
tablet when it comes in contact with aqueous fluid and this process of
desegregation of constituent particles before the drug dissolution occurs, is
known as disintegration process and excipients which induce this process are
known as disintegrants.
The objectives behind addition of
disintegrants are to increase surface area of the tablet fragments and to
overcome cohesive forces that keep particles together in a tablet.
Mechanism of tablet disintegrants:24
The tablet breaks to primary particles by one or more of
the mechanisms listed below:-
Ø
By
capillary action
Ø
By
swelling
Ø
Because
of heat of wetting
Ø
Due
to disintegrating particle/particle repulsive forces
Ø
Due
to deformation
Ø
Due
to release of gases
BY CAPILLARY ACTION:24
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 into
fine particles. Water uptake by tablet depends upon hydrophilicity of the drug
/excipient 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 particles.
BY SWELLING:24
Perhaps the most widely accepted
general mechanism of action for tablet disintegration is swelling Tablets with
high porosity show poor disintegration due to lack of adequate swelling force.
On the other hand, 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.
Fig.
No 3: Disintegration Of Tablet By Wicking And Swelling
Because of heat of wetting (air expansion)
When disintegrants with exothermic
properties gets wetted, localized stress is generated due to capillary air
expansion, which helps in disintegration of tablet. This explanation, however,
is limited to only a few types of disintegrants and can not describe the action
of most modern disintegrating agents.
Due to disintegrating particle/particle repulsive forces
Another mechanism of disintegration
attempts to explain the swelling of tablet made with ‘non-swellable’
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.
Due to deformation24
Hess had proved that during tablet
compression, disintegranted 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 break up of the tablet. This may be a mechanism
of starch and has only recently begun to be studied.
Fig.
No 4: Disintegration By Deformation And
Repulsion
Due to release of gases
Carbon dioxide released within tablets
on wetting due to interaction between bicarbonate and carbonate with citric
acid or tartaric acid. The tablet disintegrates due to generation of pressure
within the tablet. This effervescent mixture is used when pharmacist needs to
formulate very rapidly dissolving tablets or fast disintegrating tablet. As
these disintegrants are highly sensitive to small changes in humidity level and
temperature, strict control of environment is required during manufacturing of
the tablets. The effervescent blend is either added immediately prior to
compression or can be added in to two separate fraction of formulation.
The
introduction of fast dissolving dosage forms has solved some of the problems
encountered in administration of drugs to the pediatric and elderly patient,
which constitutes a large proportion of the world's population. Hence, patient
demand and the availability of various technologies have increased the market
share of Fast dissolving tablets, which in turn prolongs the patent life of a
drug. Keeping in view of the advantages of the delivery system, rapidly
disintegrating dosage forms have been successfully commercialized, and because
of increased patient demand, these dosage forms are expected to become more
popular.
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Received on
08.05.2009
Accepted on
10.07.2009
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Research
Journal of Pharmaceutical Dosage Forms and Technology. 1(2): Sept.-Oct. 2009,
67-70