FIELD OF THE INVENTION
The present invention relates to orally disintegrating pharmaceutical compositions of
Escitalopram and salts thereof and methods for the manufacture of such orally
disintegrating pharmaceutical compositions.
BACKGROUND OF THE INVENTION
Escitalopram is a selective, centrally acting serotonin (5-hydroxytryptamine; 5-HT)
reuptake inhibitor. It is marketed as Lexapro® tablets in the United States for the
treatment of Major depressive disorder and Generalized anxiety disorder.
Escitalopram was first disclosed in U.S. Pat. No. 4,943,590.
Orally disintegrating pharmaceutical compositions including granules, tablets are
convenient oral delivery systems designed to disintegrate rapidly upon contact with
aqueous fluids, e.g. water or saliva, to form a dispersion, which can be swallowed easily.
Orally disintegrating pharmaceutical compositions are particularly advantageous for
patients e.g. pediatric or geriatric patients, having difficulty in swallowing conventional
tablets or capsules, or for individuals who may not have difficulty in swallowing but may
have an aversion to swallowing conventional tablets or capsules. Orally disintegrating
pharmaceutical compositions are also convenient under circumstances in which taking an
oral dosage form with water may be inconvenient (e.g. while working or traveling).
Conventional orally disintegrating tablets are typically formed by compression (e.g., in a
tablet press). It is desirable for such tablets to have sufficiently high hardness and
sufficiently low friability to provide structural stability for transportation and storage.
Low friability (which is measured based on the percent tablet weight loss after a certain
number of revolutions in a friabilator) is desirable in that it is generally indicative of high
tablet strength. High porosity of the tablet structure also is desirable in that it allows
fluids (e.g., aqueous or bodily fluids, e.g., water or saliva) to be drawn or "wicked" from
the external environment and into the interstices of the tablet structure, thereby promoting
rapid and effective disintegration.
Various methods have been used to manufacture orally disintegrating tablets. Many of
these methods use unconventional equipment and complicated processing techniques

such as lyophilization and foam techniques. These methods result in fast disintegrating
tablets with poor tablet strength and low friability. This may prevent the use of
conventional packaging material and conventional packaging procedures.
US 2007/0021499 Al discloses orodispersible tablets prepared by mixing water soluble
filler and active pharmaceutical ingredient at a temperature above, around or slightly
below the melting point of the active pharmaceutical ingredient followed by cooling to a
temperature below 40 C and mixing cooled mass with other excipients and compressing
it into tablets with a hardness of at least 22 N.
US 2007/0092564 Al discloses orally disintegrating tablets prepared with pullalan as
binder and glycine as disintegrant comprising quickly freeze-drying soluble composition,
useful for providing oral-drug delivery of various drugs in disease treatment.
US 2002/0142034 Al discloses an orally disintegrable tablet comprising (i) fine granules
composition coated by an enteric coating layer and (ii) an additive, having a superior
disintegrability or dissolution in the oral cavity.
Above mentioned patent applications discloses costly and time-consuming methods of
manufacturing of an orally disintegrating dosage forms which further require special
technology, equipments etc.
As such, there exists a need for a conventional orally disintegrating pharmaceutical
compositions having sufficiently low friability and sufficiently high hardness, while
maintaining high porosity of the pharmaceutical compositions structure by using
economic and conventional equipments and techniques.
The invention provides such orally disintegrating pharmaceutical compositions.
OBJECT OF THE INVENTION
The present invention provides orally disintegrating pharmaceutical compositions of a)
Escitalopram or salts thereof as an active ingredient; b) diluent(s) selected from the group

consisting of cellulose derivatives such as microcrystalline cellulose and the like,
mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose, dicalcium phosphate and
their derivatives thereof; c) disintegrating agent(s) and d) optionally one or more suitable
pharmaceutically acceptable excipient(s).
Yet another object of the present invention provides orally disintegrating pharmaceutical
compositions comprising Escitalopram and salts thereof, as an active ingredient in an
amount from about 1% to about 25% by total weight of the composition.
Yet another object of the present invention provides orally disintegrating pharmaceutical
compositions comprising Escitalopram and/or salts thereof, wherein orally disintegrating
pharmaceutical composition is a tablet.
Yet another object of the present invention provides orally disintegrating tablet
comprising Escitalopram and/or salts thereof having low friability not more than 0.5%.
Yet another object of the present invention provides orally disintegrating tablet
comprising Escitalopram and/or salts thereof having hardness not less than 10 N.
Yet another object of the present invention provides orally disintegrating pharmaceutical
compositions comprising Escitalopram and/or salts thereof having disintegration time not
more than 120 seconds.
Yet another object of the present invention provides orally disintegrating pharmaceutical
compositions comprising Escitalopram and/or salts thereof, wherein orally disintegrating
pharmaceutical composition is in form of granules.
Yet another object of the present invention provides a method of producing orally
disintegrating pharmaceutical compositions by conventional methods known in the art.
The method of producing orally disintegrating pharmaceutical compositions comprises
direct compression, dry granulation or wet granulation.

Dry granulation method comprises mixing of Escitalopram and/or salts with diluent(s)
and optionally with other suitable pharmaceutically acceptable excipients, passing this
blend through roll compaction, milling this compacted mass through suitable sieves,
adding disintegrant(s) and other suitable pharmaceutically acceptable excipients and
finally thus obtained granules can be filled into a suitable container or can be compressed
into an orally disintegrating tablet. The method of producing orally disintegrating
pharmaceutical compositions preferably comprises Escitalopram and/or salts thereof,
diluents, disintegrating agents; optionally other suitable pharmaceutically acceptable
excipients, and solvent(s), to form a wet granulate. The wet granulate is dried, to produce
a dry granulate comprising the Escitalopram and/or salts thereof. The wet granulate
and/or dry granulate can be blended with other suitable pharmaceutically acceptable
excipients. These granules can be filled into a suitable container or can be compressed
into an orally disintegrating tablet. The most preferred method of manufacturing of an
orally disintegrating pharmaceutical compositions comprising wet granulation of
Escitalopram and/or salts thereof, diluents, disintegrating agents, binders, by fluidized
bed processor.
DETAILED DESCRIPTION OF THE INVENTION
The orally disintegrating pharmaceutical compositions of the invention typically contain
1% to 25% w/w Escitalopram as base. The orally disintegrating pharmaceutical
compositions of the invention optionally may comprise pharmaceutically acceptable
complexes, salts, polymorphs, hydrates, and solvates, of Escitalopram, preferably
Escitalopram oxalate.
The present invention provides orally disintegrating pharmaceutical compositions
comprising Escitalopram and salts thereof, as an active ingredient, diluent(s), a
disintegrating agent(s) and optionally other suitable pharmaceutically acceptable
excipient(s)
The term "orally disintegrating pharmaceutical compositions " as used herein refers to the
ability of a pharmaceutical composition (e.g., granules, a tablet for oral administration) to

disintegrate rapidly when contacted with a fluid, particularly an aqueous fluid (e.g.,
water, bodily fluids (e.g., saliva), and the like), to form a suspension, slurry or dispersion,
which facilitates administration of the contents of the composition (e.g., by forming a
suspension, slurry or dispersion, which is easily swallowed).
The orally disintegrating pharmaceutical compositions of the present invention can either
be granules alone that can be filled into a suitable container preferably a sachet or
granules can further be compressed into a tablet.
According to the present invention, oral granular formulations such as granules, powders
and fine granules can also be prepared.
The term "orally" includes the region within the interior of the mouth, including, but not
limited to, the buccal cavity (e.g., anterior to the teeth and gums) as well as the sublingual
and supralingual spaces, and the like.
The pharmaceutical compositions of the present invention preferably disintegrates within
about 120 seconds or less, when contacted with an aqueous fluid (e.g., water, saliva, or a
buffered solution), to form a slurry, a dispersion or a suspension, which can be
administered (e.g., swallowed) easily. The disintegration time of the pharmaceutical
compositions of the present invention can range from within about 2 seconds to within
about 120 seconds, e.g., from within about 2 seconds to within about 60 seconds, or from
within about 2 seconds to within about 30 seconds, as measured in by the Standard USP
Disintegration Test Apparatus.
The pharmaceutical compositions of the present invention more preferably disintegrates
from within about 2 seconds to within about 30 seconds, and still more preferably from
within about 2 seconds to within about 20 seconds, and most preferably from within
about 2 seconds to within about 10 seconds, as measured in by the Standard USP
Disintegration Test Apparatus.
The friability of the orally disintegrating tablet of the present invention preferably is not
more than about 1 %, more preferably about 0.8 %, and most preferably about 0.5 %

Hardness refers to the diametral breaking strength as measured by conventional
pharmaceutical tablet hardness determination methods, which are well known in the art.
A higher hardness value, sometimes measured in Newtons (N), generally is indicative of
higher diametric strength. The hardness of the tablet of the present invention preferably
ranges from about 35 N to about 30 N, and more preferably from about 25 N to about 20
N, and most preferably from about 15 N to about 10N.
Diluents may be for example various cellulose derivatives such as microcrystalline
cellulose and the like, mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose,
dicalcium phosphate and their derivatives thereof.
Disintegrants may be for example starch or its derivative like pregelatinised starch,
sodium carboxymethyl starch, sodium starch glycolate and the like, various cellulose
derivatives crosslinked sodium carboxy methyl cellulose, low substitute hydroxypropyl
cellulose, cross carmellose calcium and the like, crosspovidone and the like, alginic acid
and various ion exchange resins.
The other suitable pharmaceutically acceptable excipients of the compositions of the
present invention can also include other materials such as binding agents, taste masking
agents, anti-adherents, lubricants, sweeteners, flavors and co-processed excipients.
Binding agents may be, for example, various cellulose derivatives such as low molecular
weight hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose
and the like, methacrylate copolymers, amino alkyl methacrylate copolymers and the like,
povidone and the like, sodium alginate and the like.
Taste masking agent may be, for example, various cellulose derivatives such as low
molecular weight hydroxypropyl methyl cellulose, hydroxypropyl cellulose,
hydroxyethyl cellulose and the like, methacrylate copolymers, amino alkyl methacrylate
copolymers and the like, povidone and the like.
Antiadherents may be, for example, colloidal silicon dioxide, talc and the like.

Lubricants may be, for example, talc, magnesium stearate, calcium stearate, stearic acid,
sodium stearyl fumarate and the like.
Sweeteners may be for example aspartame, acesulfam potassium, sucralose, xylitol,
saccharine, saccharine potassium, sugars and the like.
Flavors may be for example mint flavors, orange flavor, lemon flavor, banana flavor,
strawberry flavor, magnasweet, grape flavor and the like.
Solvents may be for example aqueous or non-aqueous or their mixtures thereof.
Nonaqueous solvents for example may be isopropyl alcohol, acetone and the like.
Co-processed excipients may be for example CELLACTOSE ® 80 (75% lactose
monohydrate & 25% cellulose powder), StarLac (85% Lactose monohydrate & 15%
Maize Starch), Formax™ (Calcium carbonate / Sorbitol (70:30), Ludiflash® (Mannitol,
crospovidone, polyvinyl acetate and povidone).
Following are the non-limiting examples of the invention:
Example 1


Brief manufacturing process:
1. Sift separately Escitalopram oxalate, microcrystalline cellulose and
croscarmellose sodium through 40# S.S. sieve and mix in a suitable granulator or
fluid bed processor.
2. Dissolve amino methacrylate copolymer in mixture of Isopropyl alcohol and
Water (70:30). Granulate the blend at step 1 with this solution.
3. Dry the wet mass at step 2 at 40°-50°C temperature till required LOD is achieved.
4. Mill and sift the dried granules through 40 # S.S. sieve.
5. Sift co-processed excipient (Mannitol, crospovidone, polyvinyl acetate and
povidone), Xylitol, Sucralose and both the flavours through 40# s.s. Sieve. Mix
these ingredients with the granules at step 4.
6. Sift Talc and Magnesium stearate through 40-# S.S. sieve and mix with blend of
step 5.
7. Compress into tablets using suitable punch.
Example 2


Brief manufacturing process:
1. Sift Escitalopram Oxalate, Amino methacrylate copolymer, Co-processed
excipient {Calcium carbonate / Sorbitol (70:30)}, xylitol and croscarmellose
sodium through 40 # sieve.
2. Mix well and roll compact the step 1 blend and mill it through 30 # sieve.
3. Add microcrystalline cellulose, Croscarmellose sodium, Banana Flavor and
Aspartame to blend of step 3.
4. Mix blend of step 2 and 3 and finally lubricate with talc and magnesium stearate
and compress the resultant blend.
Example 3

Brief manufacturing process:
1. Sift Escitalopram Oxalate, Amino methacrylate copolymer, Co-processed excipient
(Mannitol, crospovidone, polyvinyl acetate and povidone), Sucralose and
crosscarmellose sodium through 40 # sieve and mix well.
2. Add microcrystalline cellulose, Mint Flavor and Aspartame to blend of step 1.
3. Mix and finally lubricate blend of step 2 with talc and magnesium stearate and
compress the resultant blend.

We Claim:
1. An orally disintegrating pharmaceutical composition comprising a) Escitalopram
or salts thereof as an active ingredient; b) diluent(s) selected from the group
consisting of cellulose derivatives such as microcrystalline cellulose and the like,
mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose, dicalcium phosphate
and their derivatives thereof; c) disintegrating agent(s) and d) optionally one or
more suitable pharmaceutically acceptable excipient(s).
2. An orally disintegrating pharmaceutical composition according to claim 1
comprises a) Escitalopram or salts thereof as an active ingredient wherein
escitalopram or salts thereof is present in amount from about 1% to 25% by
weight of the total composition.

3. An orally disintegrating pharmaceutical composition according to claim 1 is a
tablet dosage form.
4. An orally disintegrating pharmaceutical composition according to claim 1
wherein disintegrating agents comprising of starch or its derivative like
pregelatinised starch, sodium carboxymethyl starch, sodium starch glycolate and
the like, various cellulose derivatives crosslinked sodium carboxy methyl
cellulose, low substitute hydroxypropyl cellulose, cross carmellose calcium and
the like, crosspovidone and the like, alginic acid and various ion exchange resins.
5. An orally disintegrating pharmaceutical composition according to claim 1
wherein other suitable pharmaceutically acceptable excipients of the compositions
comprises binding agent(s).
6. An orally disintegrating pharmaceutical composition according to claim 5
wherein binding agents comprises various cellulose derivatives such as low
molecular weight hydroxypropyl methyl cellulose, hydroxypropyl cellulose,
hydroxyethyl cellulose and the like, methacrylate copolymers, amino alkyl
methacrylate copolymers and the like, povidone and the like, sodium alginate and
the like.

7. An orally disintegrating pharmaceutical composition according to claim 3 having
friability of not more than 0.5%.
8. An orally disintegrating tablet according to claim 3 having hardness not less than
10N.
9. An orally disintegrating pharmaceutical composition according to claim 1 having
disintegration time not more than 120 seconds.
10. An orally disintegrating pharmaceutical composition according to claim 1 is in
form of granules.
11. A method of manufacturing of an orally disintegrating pharmaceutical
composition comprising a) Escitalopram and/or salts thereof, diluents,
disintegrating agents, binders, and solvent (s), to form a wet granulate; b) drying
of wet granulate, to produce a dry granulate comprising the Escitalopram and/or
salts thereof; c) blending of dry granulate with other ingredients, wherein the
granules can be filled into a sachet or can be compressed into a dosage form.
12. A method of manufacturing of an orally disintegrating tablet according to claim
11 comprising a) wet granulation of Escitalopram and/or salts thereof, diluents,
disintegrating agents, binders, and a solvent, to form a wet granulate by fluid bed
processor.

An orally disintegrating pharmaceutical composition comprising Escitalopram or salts
thereof as an active ingredient; diluent (s) selected from the group consisting of cellulose
derivatives such as microcrystalline cellulose and the like, mannitol, lactose, dextrose,
sorbitol, starch, xylitol, maltose, dicalcium phosphate and their derivatives thereof;
disintegrating agent(s) and optionally one or more suitable pharmaceutically acceptable
excipient(s). A method of manufacturing of an orally disintegrating pharmaceutical
composition comprising Escitalopram and/or salts thereof, diluents, disintegrating agents,
binders, and solvent (s), to form a wet granulate; drying of wet granulate, to produce a
dry granulate comprising the Escitalopram and/or salts thereof; blending of dry granulate
with other ingredients, wherein the granules can be filled into a sachet or can be
compressed into a dosage form.