MDDS

Mouth dissolving drug delivery

system - a novel drug delivery system achieved
by direct compression method

NADANASABAPATHI.P.,
M.Pharm
Jr.Research.asst
APEX LABORATORIES
(P)LTD,CHENNAI.
WHAT IS MDDS ?
A mouth dissolving drug delivery system,
is a tablet that dissolves or disintrigrants in
the oral cavity without the need of water or
chewing.
Most mouth dissolving delivery system
must include substances to mask the taste
of the active ingredient. This masked
active ingredient is then swallowed by the
patient's saliva along with the soluble and
insoluble excipients
 What the ideal requirements?
• On oral administration its dissolve /
disperse/ disintegrate in mouth in a matter
of seconds without necessitate of water .
• Have a pleasing mouth feel.
• Have an acceptable taste masking
property.
• Be harder and less friable
• Leave minimal or no residue in mouth after
administration
• Have physical and environmental stability
what are the advantages over the conventional
dosage form?

• Convenient for administration and patient compliant.

• No need of water to swallow the dosage from.
• Good mouth feels can achieve.
• Rapid dissolution of drug and absorption which may
produce rapid, onset of action.
• Ability to provide advantages of liquid medication in
the form of solid preparation.
• improved bioavailability by pregastric absorption.
• New business opportunity like product
differentiation, product promotion, patent extension
and life cycle management.
How dissolves faster?
• In fast dissolving tablets, water must moves
quickly into the tablet matrix to cause rapid
disintegration and instantaneous dissolution of
the tablet.
• Maximizing the porous structure of the tablet
matrix and incorporating an appropriate
disintegrating agents or highly water soluble
excipients in the tablet formulation are the basic
approaches used in current fast dissolving tablet
technologies.
• Basically, the disintegrant’s major function is to
oppose the efficacy of the tablet binder and the
physical forces that act under compression to
form the tablet.
What are disintegrant ?

Disintegrants are agents added to tablet

(and some encapsulated) formulations to
promote the breakup of the tablet (and
capsule “slugs’) into smaller fragments in
an aqueous environment thereby
increasing the available surface area and
promoting a more rapid release of the drug
substance.
In what mechanisms a disintegrants
disintegrates?
• Swelling- on contact with water it tendency to swells
and decrease the adhesiveness of the tablet.
• Porosity-pathways for the penetration of fluid into
tablets its impart their disintegrating action.
• Capillary Action- (Wicking) Liquid is drawn up
through capillary action and rupture the
interparticulate bonds causing the tablet to break
apart.
• Deformation-the compression forces involved in
tableting causes deformation more permanently
which on exposure to water leads disintegration.
Example for disintegrants
• Starch
• Lactose
• Polacrilian K
• Sodium alginate
• Pregelatinized Starch (Starch 1500)  
• Microcrystalline Cellulose (Avicel)  
• Chitosan
• Docusate sodium etc…
Super Disintegrants ! – which are decreases the
disintegration time by various mechanism especially
swell to many times their original size when placed in
water while producing minimal viscosity effects

1. Modified Starches- Sodium Carboxymethyl Starch

(Chemically treated Potato Starch)
     Eg. Sodium Starch Glycolate (Explotab, Primogel)
Mechanism of Action: Rapid and extensive swelling
with minimal gelling.
Effective Concentration: 4-6%. Above 8%,
disintegration times may actually increase due to gelling
and its subsequent viscosity producing effects.
2. Cross-linked polyvinylpyrrolidone- water insoluble
and strongly hydrophilic.
Eg. crospovidone (Polyplasdone XL, Kollidon CL)
Mechanism of Action: Water wicking, swelling and
possibly some deformation recovery.
Effective Concentration: 2-5% in both wet & dry
granulation.

3. Modified Cellulose- Internally cross-linked form of

Sodium carboxymethyl cellulose.
 Eg. Ac-Di-Sol (Accelerates Dissolution), Nymcel
Mechanism of Action: Wicking due to fibrous structure,
swelling with minimal gelling.
Effective Concentrations: 1-3% (Direct Compression), 2-
4% (Wet granulation)
What is mean by direct Compression method?

• The term “direct compression” is defined as the

process by which tablets are compressed
directly from powder mixture of API with suitable
excipients.
• No pretreatment of the powder blend by wet or
dry granulation procedure is required.it done by
simple mixing of API with suitable additive and
compress to tablets.
 Merits
1)Direct compression is more
efficient and economical
process as compared to other
processes
2)The most important
advantage of direct
compression is economical
process
3)Chemical stability problems
for API and excipient would be
avoided.
4)Prime particle dissolution.
5)Particle size uniformity.
6)The chances of batch-to-
batch variation are negligible
Demerits
1) Problems in the uniform
distribution of low dose drugs.
2) High dose drugs having high
bulk volume, poor
compressibility and poor
flowability are not suitable for
direct compression.
3) The choice of excipients for
direct compression is
extremely critical
4) Many active ingredients are
not compressible either in
crystalline or amorphous
forms
5) Non-uniform distribution of
colour, especially in tablets of
deep colours
What are the additives required for direct
compression ?
• Directly compressible materials (Spray dried lactose,
Anhydrous lactose, Starch-1500, Sorbitol ,
microcrystalline cellulose, Di-Pac )
• Binders ( Copovidone, Cellulose, Povidone, Starch,
HPMC etc)
• Disintegrants (Starch, Lactose, Polacrilian K, Sodium
alginate, Pregelatinized Starch,Microcrystalline
Cellulose)  
• Lubricants (magnesium stearate, stearic acid, Talc etc...)
• Antimicrobial preservatives ( MPS, PPS, Potassium
sorbate)
• Sweeteners (Aspartame, Neotame, Saccharin sodium,
Sucralose, etc…)
• Some other additives are used depend upon the
formulations.
 What are manufacturing steps involved in
Direct Compression ?
• Milling of drug and excipients.
• Mixing of drug and excipients.
• Tablet compression.

Sieving Milling Mixing Compression

Evaluation Of Blends
Angle of Repose

• the maximum angle possible between the surface of

the pile of the powder and the horizontal plane.
• The angle of repose was determined by the funnel
method suggested by Newman. Angle of repose is
determined by the following formula
Tan θ = h/r
Therefore       θ = Tan-1 h/r
Where            θ = Angle of repose
h = height of the cone
r= Radius of the cone base
• Angle of Repose less than 30 ° shows the free flowing
of the material
 Bulk Density
• Density is defined as weight per unit volume. Bulk
density (pb) is defined as the mass of the powder divided
by the bulk volume and is expressed as gm/ cm 3 .
• A sample of about 50 cm 3 (blend) is carefully introduced
in a 100ml graduated cylinder. The cylinder is dropped
onto a hard wood surface three times from a height of 1
inch at two second interval. The bulk density is then
obtained by dividing the weight of sample in gm by final
volume in cm 3
Pb = M/ V
• Where                        pb = Bulk Density "
                                 M = Weight of sample in gm
                                 Vo   = initial volume of blend in cm 3
• Bulk density is very important in designing the size of
containers needed for handling, shipping, and storage of
raw material and blend.
 Bulkiness
• Specific bulk volume or reciprocal of bulk density is called bulkiness or
bulk.
• Bulkiness increases with a decrease in particle size. In mixture of material
of different sizes, however the smaller particle shifts between the larger
particles and tends to reduce the bulkiness.
• The bulkiness can be calculated by the following formula
• Bulkiness=      I/ pb where, pb = Bulk Density.

Void Volume
• The volume of the spaces is known as the void volume "v"
and is given by the formula
• V= Vo- Vf
• Where Vo = Bulk volume (volume before tapping)
• Vf   = True volume (volume after tapping
 Compressibility index

• Compressibility index is an important measure that can be

obtained from the bulk and tapped densities.
• CI = 100 (VO – Vf)
V

% Comp. Index Properties

5-12 Free flowing
12-16 Good
18-21 Fair
23-35 Poor
33-38 Very poor
>40 Extremely poor
Process Related problems occuring in Direct
compression ?
• Capping, lamination, splitting, or
layering of tablets is sometimes related
to air entrapment during direct
compression.
• When air is trapped, the resulting tablets
expand when the pressure of tablet is
released, resulting in splits or layers in the
tablet.
What are the parameters evaluation
in mouth dissolving tablets ?
1)Shape of Tablets:
The compressed tablets were examined under
the magnifying lens for the shape of the tablet.
2) Tablet Dimensions:
Thickness and diameter were measured using
a calibrated dial caliper.
3) Hardness:
Hardness indicates the ability of a tablet to
withstand mechanical shocks while handling. The
hardness of the tablets was determined using
monsanto hardness tester. it is expressed in
kg/cm2.
 4) Friability Test:
It is measured of mechanical strength of tablets.
Roche friabilator was used to determine the friability by
following procedure.
A preweighed tablet was placed in the friabilator.
friabilator consist of a plastic-chamber that revolves at 25
rpm, dropping those tablets at a distance of 6 inches with
each revolution. The tablets were rotated in the friabilator
for at least 4 minutes. At the end of test tablets were dusted
and reweighed,
The loss in the weight of tablet is the measure of
friability and is expressed in percentage as
%Friability = loss in weight / Initial weight x 100 Percentage
friability of tablets less than 1% is considered acceptable.
.
 5)Weight Variation Test:

• Twenty tablets were selected randomly from

each batch and weighed individually to check for
weight variation. The following percentage
deviation in weight variation is allowed.

Average weight of a tablet ±Percentage deviation

130 mg or less 10
>130mg and <324mg 7.5
324 mg or more 5
6) Disintegration test
• 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 any mass remaining in the
apparatus was measured in seconds.

7) Dispersion time
• In vitro dispersion time was measured by dropping
a tablet in a beaker containing 50 ml of Sorenson's
buffer pH 6.8. Three tablets from each formulation
were randomly selected and in vitro dispersion time
was performed.
Packaging
• Expensive packaging, specific processing, and
special care are required during manufacturing
and storage to protect the dosage of other fast-
dissolving dosage forms.
• Unlike these other 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
Marketed Fast Dissolving Tablets in India
Name of the
Product Active Ingredients
Imodium Lingual Imodium
Pepcidin Rapitab Quick releasing antiulcer
preparation of pepcid
Mosid – MT Mouth melt tablet of Mosapride
citrate.
Calritin Reditabs Immediate Dissolving formulation of Calritin
Nimulid – MD Nimesulide
Zyrof Meltab Rofecoxib
Claritin Reditab micronized loratadine
Feldene Melt piroxicam (10 or 20 mg),
Maxalt-MLT rizatriptan (5 or 10 mg),
peppermint flavour
Pepcid RPD famotidine (20 or 40 mg),
Zyprexa Zydis olanzapine (5, 10, 15 or 20 mg),
Zofran ODT ondansetron (4 or 8 mg),
strawberry flavor
Remeron Soltab mirtazepine (15, 30, or 45 mg),
orange flavor