FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(Sec section 10 and rule 13)
1. TITLE OF THE INVENTION: "A pharmaceutical composition"
2. APPLICANT
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Indian
Companies ACT, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumhai - 400 008,
Maharashtra, India
3.PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner
in which it is to be performed:


Technical Field:
The present invention relates to formulating drugs e.g. Mirtazapine as fast mouth
dissolving tablets suitable for oral use.The present invention also relates to processes for
their preparation and the use of such a formulation in the treatment of depression. This
invention further provides a tablet for oral use with mirtazapine in combination with an
antipsychotic agent or analgesics or non steroidal anti-inflammatory drug or histamine
H2-receptor antagonist.
Background and Prior art
Mirtazapine, is chemically known as 1,2,3,4,10,14 D-hexahydro-2-methylpyrazo [2,la]
pyrido [2,3-c] [2] benzazepine. Mirtazapine is known for the treatment of depression. As
an anti-depressant, mirtazapine is a noradrenergic and specific serotonergic
antidepressant that enhances both noradrenergic and serotonergic neurotransmission by
means of antagonism at presynaptic a2-adrenoceptors while blocking postsynaptic
serotonin 5-HT2 and 5-HT3 receptors.
Mirtazapine tablets are generally acceptable with respect to their medicinal activity and
has been a safe, well- tolerated drug. The strength of the active ingredient ranges from 15
to 45 mg mirtazapine. Side-effects associated with mirtazapine, include appetite increase,
weight gain, daily somnolence, sexual dysfunction, gastro-intestinal side-effects, edema,
restless legs, dry mouth, excessive sedation.
The compound can be prepared as disclosed in U. S. Pat. No. 4,062,848 to van der Burg.
One of the formulation patents containing mirtazapine mentions Patent no. HK1047547,
which relates to a combination comprising paracetamol or a non-steroidal anti-
inflammatory drug (NSAID) and mirtazapine, whereby paracetamol or an NSAID and
mirtazapine are present in the combination in such amounts that the effect of the
composition is more favourable than the added effects of the amounts of each drug
separately. This combination is used in the treatment of headache.
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US2003105083, relates to a combination comprising niirtazapine and gepirone. This
combination can be used in the treatment of depression and related disorders.
Specifically for mirtazapine it was desired to further improve some of its beneficial
effects, e. g. better sleep, and a stronger anxiolytic effect, and to achieve an earlier onset
of antidepressant action. The latter is of particular importance in psychiatry. .
With increased average human life span, drug administration for elderly patients is of
increasing importance. Old age is usually accompanied by the onset of degenerative
pathologies involving coordination difficulties and difficulty in swallowing the
conventional dosage forms like tablets or capsules. Swallowing problems are also present
in children as well. Dosage forms with quick onset of action are also felt in patients with
no swallowing problems. Fast dissolving or disintegrating tablets provides the solution to
such problems. These tablets disintegrate quickly in saliva or water.
EP 436 252 discloses powdered particulates or granules useful for the preparation of an
oral liquid pharmaceutical formulation of mirtazapine. These granules, when introduced
in specified quantity of water and agitated, provide readily drinkable suspensions of
mirtazapine. EP 431 663 discloses a stabilized solution of mirtazapine suitable for
parenteral or peroral administration.
MXPA02003519, relates to a oral dosage unit comprising mirtazapine, wherein the
dosage unit is of the orally disintegrating type. The dosage unit, while rapidly
disintegrating upon oral administration, is bioequivalent with conventional tablets. These
formulations are highly porous in nature and having low moldability, thereby making the
tablets brittle.
Different techniques are used to prepare fast dissolving tablets. Most of these techniques
aim at making porous particles/granules or tablets, so that mouth dissolving time can be
reduced. Freeze drying, spray drying, sublimation, disintegrant addition, shearform
technology and tablet molding are examples of such techniques.
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Also self disintegrating tablets and/or chewables, present real taste masking problems as
chewing can disrupt protective coatings. They are often Very soft making it difficult and
expensive to formulate, package and store. In addition, particularly as compared to tablets
which are swallowed, taste masking can become a significant obstacle due to the length
of exposure in the patient's mouth.
There are a variety of ways of taste masking various drugs. E.g. the use of flavorings,
sweeteners, effervescent systems and various coating strategies. Some of these taste
masking strategies cannot adapt well to the demands of rapidly dissolvable dosage forms
and/or can be quite expensive.
Modified celluloses such as hydroxypropylmethyl-cellulose (HPMC), ethylcelluloses and
mixtures of such celluloses have been used to produce eyerie coatings/taste masking as
well as coatings to provide a controlled drug release. Controlled release results in either
an extended release or a rapid release in the small intestine- Such coatings have also been
used in taste masking but are ineffective in case of orally disintegrating tablets.
It is believed that, when a tablet is exposed to saliva in the mouth, during the
disintegration of the tablet, at least a portion of the coating dissolves or swells, thereby
exposing the offending drug to the patient's taste buds. Another agent, Eudragit El00
which is a mixture of methylaminoethyl methacrylate and neutral methacrylic acid ester
has also been known for use in taste masking, particularly in combination with celluloses
such as a cellulose esters. However, these mixtures, as well as Eudragit El 00 alone, were
found to be ineffective in providing taste masking when using certain objectionable
tasting drugs.
In general, ion exchangers suitable for use in ion exchange chromatography and for such
applications as deionization of water are suitable for use in these controlled release drug
preparations. Adsorption of the drug onto the ion exchange resin particles to form the
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drug/resin complex is a well known technique as discussed in U.S. Pat. Nos. 2,990,332
and 4,221,778.
Therefore there still remains a need for effective taste masking strategies, particularly for
use with aggressively bad tasting drugs, which lend themselves to in-mouth rapidly
dissolving dosage forms.
Hence, the present invention aimed to provide one such solution of taste masking of bitter
tasting drugs such as mirtazapine by complexing with anion-exchange resin thereby
achieving desired result, and also formulated the same as fast mouth dissolving tablet to
get quicker onset of action.
Objectives of the Invention:
The object of the present invention aimed to provide a hard, compressed, rapidly
dissolvable dosage form for quicker on set of action, adapted for direct oral dosing
wherein the active ingredient is Mirtazapine, its salt, solvate, enantiomer or derivative
thereof, alone or optionally in combination with another active ingredient and complex is
formed between mirtazapine, its salt, solvate, enantiomer or derivative thereof with a
pharmaceutically acceptable ion exchange resin for taste masking.
Another object of the present invention is to provide a method of making a packaged,
robust, orally dissolvable tablet dosage form.
Yet another object of this invention is to provide a pharmaceutical formulation, in the
form of a tablet, sachet or powder for suspension dosage form, which comprises of
mirtazapine-anionic resin complex and one or more pharmaceuticaily acceptable
excipients.
Yet another object of this invention is to provide a pharmaceutical formulation
comprising mirtazapine, its salt, solvate, enantiomer or derivative thereof, alone or
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optionally in combination with another active ingredient like antipsychotic agent,
analgesics, non-steroidal anti-inflammatory drugs, etc.
Summary of the invention:
The present invention discloses a pharmaceutical composition comprising mirtazapine as
active ingredient, alone or in combination with another active ingredient, wherein
mirtazapine is complexed with an ion-exchange resin to mask the bitter taste and
formulated as a fast dissolving tablet for quicker on set of action for oral use and the
method for manufacture thereof.
The invention provides a mouth dissolving tablet for oral administration wherein the
active is complexed with a pharmaceutically acceptable ion-exchange resin more
specifically an anion exchange resin.
The invention also provides a mouth dissolving tablet comprising mirtazapine which can
be optionally formulated in combination with an antipsychotic agent or analgesics, non
steroidal anti-inflammatory drug, histamine H2-receptor antagonist, ergot alkaloids,
antiserotonergics, etc
The present invention also provides a process for the manufacture of the pharmaceutical
formulation comprising mirtazapine or its salts, enantiomer, solvate form, thereof.
Detailed description of the invention:
For the purpose of more clearly defining the formulation according to the invention,
orally-disintegrating tablets are those which cannot be swallowed integrally, but
disintegrate in the mouth spontaneously or through chewing or sucking; from the
disintegrated particles the drug is released in the esophagus or the stomach, whereupon
absorption occurs via the gastro-intestinal tract; examples: effervescent tablets or
multiparticulate tablets, each with a coated or otherwise encapsulated drug, or with a drug
which inherently is not absorbed via the mucosa.
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According to the invention a mirtazapine dosage form is provided which is fundamentally
comparable with the existing regular compressed tablets, however with the unexpected benefits
found with oral disintegration for quicker on set of action. Orally-disintegrating pharmaceutical
formulations in themselves are known to the person skilled in the art. The means which
substantially prevent mirtazapine from being released orally have a function in preventing
mirtazapine from being absorbed as in the case of a sublingual or buccal formulation. Although,
in theory, e. g. a salt of mirtazapine might be devised which could prevent oral absorption, it is
preferred that the compound itself remains unaltered, and the means to prevent oral release
actually shields mirtazapine until it has been swallowed.
An "orally disintegrating dosage unit" is a term which distinguishes the type of dosage
units with which the invention is concerned from conventional tablets. The term thus
refers to dosage units which, upon peroral administration, disintegrate in the mouth
and/or the esophagus, rather than in the stomach or the gastro-intestinal tract. This can
generally be associated with a disintegration time of less than 60 seconds. Examples
include effervescent tablets, fast-dissolving, fast-melting tablets, sublingual tablets.
Adsorption of the drug onto the ion exchange resin particles to form the drug/resin
complex is a well known technique which can be used. The drug is mixed with an
aqueous suspension of the resin, and the complex is then washed and dried. Adsorption of
drug onto the resin may be detected by measuring a change in the pH of the reaction
medium, or by measuring a change in concentration of sodium or drug.
The ion exchange resins suitable for use in these preparations are water-insoluble and
consist of a pharmacologically inert organic or inorganic matrix containing covalently
bound functional groups that are ionic or capable of being ionized under the appropriate
conditions of pH. The organic matrix may be synthetic (e.g., polymers or copolymers of
acrylic acid, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene), or partially
synthetic (e.g., modified cellulose and dextrans). The inorganic matrix can also be, e.g.,
silica gel modified by the addition of ionic groups. The covalently bound ionic groups
may be strongly acidic (e.g., sulfonic acid), weakly acidic (e.g., carboxylic acid), strongly
basic (e.g.. quaternary ammonium), weakly basic (e.g., primary amine), or a combination
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of acidic and basic groups. In general, those types of ion exchangers suitable for use in
ion exchange chromatography and for such applications as deionization of water are
suitable for use in these controlled release drug preparations.
The drug/resin complex has a ratio of Mirtazapine to resin of about 1:0.5 to about 1:4,
preferably about 1:2. The only limit to using ratios in excess of 1:6 is an economic and
aesthetic one.
The present invention can be used for any material whether objectionable tasting or not.
Mirtazapine is an extremely bitter drug and hence the need to mask the taste. Formulating
solid dosage delivery systems like capsules and coated tablets seem a better option to
deliver such bitter drugs, but it may be inconvenient to administer to children and
geriatrics as these individuals experience difficultly in swallowing solid oral dosage
forms. Hence formulations comprising mirtazapine in a form that is chewable or a fast
mouth dissolving tablet is justifiable. Suitable formulations comprising mirtazapine
dispersed in liquid include liquid formulations such as suspension, sachets and dispersible
tablets can be formulated.
In view of the alkaline nature of mirtazapine, the compound has been found to be
surprisingly suitable for complexing with polacrilin potassium and in the highly acidic
environment of the stomach, releases mirtazapine.
Representative resins useful in this invention include Amberlite IRP-69 (obtained from
Rohm and Haas) and Dow XYS-40010.00 (obtained from The Dow Chemical Company).
Both are sulfonated polymers composed of polystyrene cross-linked with 8% of
divinylbenzene, with an ion exchange capacity. The amount of the drug bonded to the ion
exchange resin is in the range from about 25 to about 75% by weight of the drug/resin
complex and more preferably, is in the range from about 33 to about 77% by weight of
the drug/resin complex. Most preferably, the amount of the drug bonded to the ion
exchange resin is in the range from about 40 to about 60% by weight of the drug/resin
complex.
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The pharmaceutical composition of the present indention comprises the resin
concentration preferably in the range from 0.2% to 10.0% by weight of the composition.
AMBERLITE IRP 88, an acrilin potassium resin can br used to form a stable taste
masked complex with Mirtazapine and this complex has Acceptable bioavailability when
compared to the conventional swallow tablet.
Accordingly, the present invention provides an oral fast mouth dissolving solid
pharmaceutical composition comprising a mirtazapine-AMBERLITE IRP-88 complex.
AMBERLITE IRP-88 is commercially available from Rohm & Haas in a
pharmaceutically acceptable grade.
The fast dissolving tablets of the present invention can either be produced by
conventional methods like wet granulation, dry granulatio" and direct compression or by
specialized techniques like tablet molding and freeze drying-
The optional pharmaceutical excipients of this invention may be selected, but are not
limited to diluents, binders, disintegrants, lubricants, grants, adhesives, colouring
agents, flavouring agents, solvents, preservatives, sweeteners and miscellaneous materials
such as buffers and adsorbents which are chemically and physically compatible with
mirtazapine.
The granules used to make the tablets of the present indention are prepared from low
density alkali earth metal salts, low density water soluble carbohydrates and mixtures
thereof. The low density alkali earth metal salts of the present invention are known to
those skilled in the art. Non-limiting examples of alkali earth metal salts include calcium
carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium
silicate, magnesium aluminate. aluminum hydroxide, aluminum magnesium hydroxide,
dibasic calcium phosphate etc.
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The present invention has materials such as macrocrystalline cellulose, microcrystalline
dextrose, mannitol, directly compressible calcium phosphate, amylase,
polyvinylpyrrolidone and the iike have properties which aid in formulating tablets.
Disintegrants preferred for the present invention may be selected from starches or
modified starches such as sodium starch glycolate, corn starch, potato starch or
pregelatinized starch; clays such as bentonite. montmorillonite or veegum; celluloses
such as microcrystalline cellulose, hydroxypropyl cellulose or carboxymethyl cellulose ;
algins such as sodium alginate or alginic acid; crosslinked cellulose such as
croscarmellose sodium; gums such as guar gum or xanthan gum; cross-linked polymers
such as crospovidone; effervescent agent such as sodium bicarbonate and citric acid; or
mixtures thereof.
The preferred disintegrant for the present invention is crospovidone (polyvinyl
pyrrolidone ("PVP") which is water insoluble. While they add to the rapid disintegration
of the formulation, their inclusion can also add to the total content of insoluble
ingredients making it more difficult to strike a balance between disintegration/dissolution
speed and the resulting organoleptic sensation. Preferably, the amount of disintegrant will
range from between about 1 to about 10% by weight based on the weight of the tablet and
more preferably between about 3 to about 7%.
Water soluble low density carbohydrates of the present invention are known to those
skilled in the art. The water soluble low density carbohydrates are preferably highly
porous and can be selected from a high moldability or low moldability type. Preferably,
the water soluble low density carbohydrate is one that has a quick disintegration and
dissolution rate in the buccal cavity and a high moldability to give adequate hardness
when produced by compression molding such as tabletting. High moldability type water
soluble carbohydrates are selected from the group consisting of maltose, maltitol and
sorbitol. Low moldability type water soluble carbohydrates are selected from the group
consisting of rnannitol, glucose, sucrose and xylitol.
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Examples of suitable lubricants/glidants include one or more of stearic acid, magnesium
stearate, calcium stearate, sodium stearyl fumarate, talc, siliconised talc, hydrogenated
caster oil, sucrose esters of fatty acid, microcrystalline wax, colloidal silicon dioxide,
polyethylene glycols, sodium lauryl sulphate, polyoxy ethylene monostearate and
equivalents thereof. The lubricants can be added in a quantity ranging from 0.5 to 5%.
Lubricants, such as magnesium stearate should also be included in an amount of less than
about 2% by weight of the finished tablet, preferably less than about 1% and most
preferably about 0. 5% by weight.
The tablets according to the present invention may also contain other excipients like
diluents (example: lactose (monohydrate, spray-dried monohydrate, anhydrous and the
like), sucrose, dextrose, mannitol, sorbitol, starch, cellulose (e.g. microcrystalline
cellulose), dihydrated or anhydrous dibasic calcium phosphate, calcium carbonate,
calcium sulfate, and others and the like).
The present invention contemplates the inclusion of those sweeteners well known in the
art, including both natural and artificial sweeteners. Thus, additional sweeteners may
include, among others, water-soluble sweetening agents such as monosaccharides,
disaccharides and polysaccharides such as xylose, ribose, glucose, mannose, galactose,
fructose, dextrose, sucrose, sugar, maltose, partially hydrolyzed starch, or com syrup
solids and sugar alcohols such as sorbitol, xylitol, mannitol and mixtures thereof; water-
soluble artificial sweeteners such as the soluble saccharin salts, i.e., sodium, or calcium
saccharin salts, aspartame, cyclamate sails. acesulfam-K and the like, and the free acid
form of saccharin and dipeptide based sweeteners such as L-aspartyl-phenylalanine
methyl ester and and the like. In general, the amount of sweetener will vary with the
desired amount of sweeteners selected for a particular tablet composition.
Suitable flavorings include both natural and artificial flavors. The flavorings are generally
utilized in amounts that will vary depending upon the individual flavor, and may, for
example, range in amounts of about 0.5% to about 3% by weight of the final composition
weight. Colourants may be optionally used in the formulation.
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Excipients used in this formulation include binders (microcrystalline cellulose, starches,
polyvinylpyrrolidone and the like). Preferably, the binder will be present in an amount
which is greater than zero and indeed, in an amount of between about 3 to about 15% and
even more preferably between about 8 and about 12%. Water soluble binders are
preferred. But generally, such binders are water insoluble. Therefore, the effort should be
made to minimize the content of such binders as the higher the overall content of
insoluble materials such as the coated active, the lower the overall organoleptic quality of
the formulation. Certain binders such as a number of insoluble filler-binders including
microcrystalline cellulose have additional advantageous properties that, despite their
insolubility, make them nonetheless more desirable than other similar binders.
The carrier liquid for binder is usually aqueous in nature. In the present invention, water
is the vehicle of choice.
The drug name mirtazapine also refers to the individual (R) and (S) enantiomers of
mirtazapine. These can be used as their salts, substantially free of the other enantiomer or
as mixtures of such enantiomers in any proportions.
Rapidly dissolvable sugar and sugar alcohol in accordance with the present invention
include, for example, mannitol, lactose, sucrose, maltose, dextrose, sorbitol, xylitol,
maltitol, lactitol, and maltodextrins. Mannitol and other similar compounds having a
negative heat of solution are preferred because they provide a particularly pleasant
sensation enhancing the organoleptic experience of taking the tablet of the present
invention. When used at all. only rapidly water soluble filler materials should be used.
However, when placed in an aqueous environment such as, in a patient's mouth, the
binder can actually aid in the disintegration of the tablet. In addition, microcrystalline
cellulose imparts an almost creamy mouth feel which helps offset the negative impact of
its insolubility. The use of such binders therefore helps reduce the overall amount of
disintegrant which needs be used. Other binders include alginic acid, sodium alginate,
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starch, modified starches and other water swellable binders. Certain binders, like
AVICEL, can also be used and classified as disintegrants as is known in the industry.
Most preferred amount of Avicel is about 5% or less by weight.
The stabilizers used in the present invention are commonly known in the industry and the
selection will depend upon the properties of the drug employed in the dosage
formulation. If the drug is sensitive to acidic environments, a basic stabilizer should be
used such as sodium dihydrogen phosphate, calcium or magnesium carbonate, arginine,
lysine or meglamine.
Wetting agents are surfactants that lower the interfacial tension and contact angle
between solid particles and liquid vehicle. According to HLB theory, the best range for
wetting and spreading by nonionic surfactant lies between 7 and 10. Use of surfactants as
wetting agent also retards crystal growth. Usual concentration of surfactant varies from
0.05% - 0.5% and depends on the solid content intended for use. The wetting agent of the
present invention can be selected from the excipients well known in the art for e.g.
sodium lauryl sulfate. poly sorb ales, etc.
The drug name mirtazapine also refers to the individual (R) and (S) enantiomers of
mirtazapine. These can be used as their salts, substantially free of the other enantiomer or
as mixtures of such enantiomers in any proportions.
The present invention can be optionally formulated with another drug/active ingredient
which may be selected from the group consisting of pharmaceuticals, nourishing and
health-promoting agents, may include antacids such as omeprazole, non-steroidal anti-
inflammatory drugs such as rofecoxib and nimesulide, steroidal anti-inflammatory drugs
such as betamethasone, anti-psychotic drugs such as olanzapine, etc.
The invention further provides the process for preparation of stable drug-ion exchange
resin complex, which comprises (i) suspending the resin in an appropriate solvent; (ii)
adding the drug to step (i) under continuous stirring; (iii) formulating a drug-resin
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complex; (iv) if required, filtration and drying of this complex. The solvent used for
dissolving the resin is preferably aqueous in nature.
The present invention provides a method of manufacture of the fast
dissolving/disintegrating tablet formulation by using standard methods i.e. wet
granulation or dry granulation and/or direct compression method.
A process for preparing a fast dissolving dosage form for oral administration comprising :
a) Dissolve polysorbate 80 in water and add the drug and Amberlite (polacrillin
potassium) to this under stirring. Stir for 2 hrs.
b) Mix Mannitol and povidone and granulate this with the drug slurry. Dry and size the
granules
c) Mix the granules with lubricants and compress using suitable tablet toolings.
The present invention also relates to a method for treating psychotic disorders in humans
and mammals disorders.
The present invention is further illustrated but not limited to the following examples: -
Example 1: Mirtazapine mouth dissolve tablet

Sr.No Name of ingredients Qty
(Mg/tab)
Part-I Dry mix
1. Mannitol 151.50
2. Crospovidone 5.00
Drug Resin Suspension
3. Mirtazapine 45.00
4. Polacrillin potassium 22.50
5. Polysorbate 80 1.00
6. Purified water q.s.
Blending and lubrication
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7. Mannitol 129.00
8. Flavours 9.00
9. Mag. Stearate 6.00
10. Aspartame 10.00
11. Avicel PH 102 150.00
12. Sod. Stearyl fumarate 6.00
13. Aerosil 5.00
14. Crospovidone 25.00
15. Dibasic sod. phosphate 15.00
Total 600mg
Process:
Polacrillin potassium was suspended in distilled water to which Mirtazapine and
polysorbate 80 was added under mixing. This was used as binder to granulate the dry mix
of mannitol and crospovidone. The granulated mass was dried, sized, blended and
lubricated with the remaining excipients. The mass was compressed using suitable
punches.
Example 2: Mirtazapine sachet

Sr.No Name of ingredients Qty
(Mg/tab)
Part-I Dry mix
1. Mannitol 151.50
2. Crospovidone 25.00
Binder
3. Mirtazapine 45.00
4. Polacrilin potassium 22.50
5. Polysorbate 80 1.00
6. Purified water q.S.
Blending and lubrication
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7. Sorbitol 50.00
8. Pregelatinised starch 25.00
9. Xylitol 0.75
10. Aspartame 0.75
11. Flavour Pineapple 2.25
12. Siliconised talc 3% 5.00
13. Mag. Stearate 3.00
14. Microcrystalline cellulose 20.0
Total 349.50mg
Process:
Polacrillin potassium was suspended in distilled water and Mirtazapine and polysorbate
80 was added under mixing. The complexed mass was filtered and dried. Dry mix of
mannitol and crospovidone was prepared and mixed with polacrilin pot.-mirtazapine
dried complex. This mass was blended and lubricated with the remaining excipients.
Example 3: Mirtazapine and paracetamol combination

Sr.No Name of ingredients Qty
(Mg/tab)
Part-I Dry mix
1. Paracetamol 125.00
2. Opadry AMB 25.00
3. PVP K-30 5.00
4. Methyl en e chloride/IPA q.s
Drug Resin Suspension
5. Mirtazapine 15.00
6. Polacrillin potassium 15.00
7. Polysorbate 80 0.35
8. Purified water q.s.
Blending and lubrication
9. Sorbitol 50.00
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10. Pregelatinised starch 25.00
11. Xylitol 0.75
12. Aspartame 0.75
13. Menthol 0.1
14. Flavour Pineappie 2.90
15. Siliconised talc 3% 5.00
16. Mag. Stearate 3.00
17 Microcrystalline cellulose 20.0
Total 360mg
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We claim,
1. A pharmaceutical composition comprising a therapeutically effective amount of
mirtazapine or its salts or enantiomers or derivatives or solvate thereof, alone or
in combination with another active ingredient, wherein mirtazapine is complexed
with an ion-exchange resin to mask the bitter taste of the drug, and formulated as
a fast dissolving tablet for oral use along with pharmaceutically acceptable
excipients to achieve quicker onset of action.
2. The composition as claimed in claiml, wherein said active ingredient is
mirtazapine.
3. The pharmaceutical composition as claimed in claims 1 and 2 , wherein the ratio
of Mirtazapine to resin is between 1:0.5 to 1:4.
4. The pharmaceutical composition as claimed in claim 1 and 3, wherein said ion-
exchange resin is an anionic resin, preferably polacrillin potassium.
5. The pharmaceutical composition as claimed in claim 1 and 4, wherein the resin
concentration ranges from 0.2% to 10.0% by weight of the formulation.
6. The pharmaceutical composition as claimed in any of the preceding claims,
wherein said formulation can be prepared by wet granulation, dry granulation and
direct compression or by specialized techniques like tablet molding and freeze
drying.
7. The pharmaceutical composition as claimed in any of the preceding claims,
wherein said formulation is prepared by wet granulation method.
8. The composition as claimed in claim 1. wherein said excipients are selected from
one or more of the following groups consisting of diluents, binders, disintegrants,
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lubricants, glidants, adhesives. colouring agents, flavouring agents, solvents,
preservatives, sweeteners, buffers and adsorbents.
9. The process for preparing stable drug-ion exchange resin complex comprising of:
(i) suspending the resin in an appropriate solvent; (ii) adding the drug to step (i)
under continuous stirring: (iii) formulating a drug-resin complex; (iv) if required,
filtration and drying of this complex.
10. The process for preparation of drug resin complex as claimed in claim 9, wherein
the solvent used for dissolving the resin is aqueous in nature.
Dated this 7th day of April

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