STABLE DISPERSIBLE FORMULATION OF ARTEROLANE MALEATE AND
PIPERAQUINE AND PROCESS OF PREPARATION THEREOF
The present invention relates to stable dispersible formulation of arterolane maleate
and piperaquine, wherein the formulation exhibits enhanced structural integrity and is
able to disperse in water within 3 minutes. The dispersible formulation presents
acceptable taste and leaves minimum residue in the mouth. The present invention also
relates to processes for preparing said dispersible formulations.
BACKGROUND OF THE INVENTION
World Health Organization currently estimates that each year malaria causes 300 to
500 million infections and over 1 million deaths worldwide. Although it has been
eradicated from the developed countries, malaria continues to extract a heavy toll of life
and health in a substantial part of the world. About 40% of the world's population lives
in areas where malaria is common such as Africa, Asia, Central America, Oceania, and
South America. Nine out of ten malaria-related deaths occur in sub-Saharan Africa and
86% of those occur in children under the age of 5. These children are susceptible to
repeated and often serious attacks of malaria. In Africa alone, a child dies every 60
seconds from malaria. Many children who survive a serious attack of malaria develop
physical and mental impairment. Low cost, commonly used therapies are increasingly
ineffective. In many sub-Saharan parts, 70 percent of malaria cases are resistant to the
low-cost existing antimalarials such as chloroquine and sulphadoxine-pyrimethamine.
The discovery of Artemisinin (qinghaosu), a naturally occurring endoperoxide
sesquiterpene lactone isolated from the plant Artemisia annua was a major
breakthrough in the malaria treatment and a number of its precursors, metabolites and
semi synthetic derivatives have also shown to possess promising antimalarial
properties. In 2006, after artemisinin had become the treatment of choice for malaria,
the WHO called for an immediate halt to single-drug artemisinin preparations in favor of
combinations of artemisinin with another antimalarial drug, to reduce the risk of
resistance development. Fixed dose artemisinin combination therapies which are
currently recommended by WHO for the treatment of uncomplicated falciparum malaria
include: artemether + lumefantrine; artesunate + amodiaquine; artesunate +
mefloquine; artesunate + sulfadoxine-pyrimethamine; dihydroartemisinin + piperaquine;
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artesunate + pyronaridine tetraphosphate. Dispersible tablets of artemether and
lumefantrine under the trade name Coartem® Dispersible have been launched by
Novartis and Medicines for Malaria Venture and is the first artemisinin based
combination therapy developed specifically for children suffering from malaria.
However, Coartem® Dispersible tablets have to be administered in a twice daily dosage
regimen based on the body weight of children. For example, for children with body
weight of 5 kg to less than 15 kg, the dosing regimen includes one tablet twice a day for
three days and for children with body weight of 15 kg to less than 25 kg, the dosing
regimen includes two tablets twice a day for three days. Thus for pediatric population
suffering from malaria, there remains a need for artemisinin based combination therapy
exhibiting a simple once a day dosing regimen.
Oral tablets have been the most preferred dosage form for administration of a wide
variety of drugs, however, certain group of patients face difficulty in swallowing these
tablets and consequently this leads to incomplete regimens. This is particularly the case
with pediatric, geriatric, mentally disabled patients and patients who are uncooperative.
In case of malaria, non-compliance may even lead to development of resistance. For
this group of patients, dispersible formulations are the most suitable dosage forms as
these combine the advantages of both dry and liquid formulations, have an acceptable
taste, offer a pleasant mouth feel and leave minimal residue in mouth after
administration.
Thus, there is a constant need for the development of dispersible formulations which
rapidly disintegrate in the mouth of the patient and/or rapidly disperse in water
rendering them convenient to ingest and achieving compliance.
The scientists of the present invention have now developed an oral dispersible
formulation of a fully synthetic artemisinin based derivative, arterolane maleate, in
combination with piperaquine. This formulation is suitable for special group of patients
who have difficulty in swallowing the conventional dosage form. Particularly, for
pediatric use, the dosing regimen of the present invention is as simple as once daily for
three days.
In particular, as disclosed earlier in our PCT Publication No. WO 2013/008218, dry
process is the preferred method for formulating oral formulation of arterolane maleate in
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combination with piperaquine. The present invention has been developed using dry
processes. Further it has been surprisingly found that the dispersible formulation
prepared in accordance with present invention not only achieves rapid disintegration
but also ensures dosage uniformity by forming a homogeneous dispersion.
SUMMARY OF THE INVENTION
In one general aspectthere is provided a stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the formulation disintegrates within 3 minutes.
In one of the embodiments, arterolane maleate and piperaquine are present in a weight
ratio of about 1:1 to about 1:10.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate in a dose range of about 20 mg to about 80 mg; and
(b) piperaquine in a dose range of about 150 mg to about 200 mg, wherein the
formulation disintegrates within 3 minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the formulation is prepared by a dry process and wherein
the formulation disintegrates within 3 minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the formulation is prepared by a direct compression
process and wherein the formulation disintegrates within 3 minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate;
(b) piperaquine;
(c) one or more filler(s);
(d) one or more superdisintegrant(s); and
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(e) one or more suspending agent(s), wherein the formulation disintegrates within 3
minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) about 2% to about 15% by weight of arterolane maleate;
(b) about 15% to about 40% by weight of piperaquine;
(c) about 30% to about 70% by weight of a filler;
(d) about 5% to about 15% by weight of a superdisintegrant; and
(e) about 1% to about 10% by weight of a suspending agent, wherein the
formulation disintegrates within 3 minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate;
(b) piperaquine;
(c) microcrystalline cellulose as filler;
(d) croscarmellose as a superdisintegrant; and
(e) water-dispersible cellulose as a suspending agent, wherein the formulation
disintegrates within 3 minutes.
In another general aspect there is provided a stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the dosing regimen for pediatrics is once daily for three
days.
In another general aspect there is provided a process for the preparation of a stable
dispersible formulation, comprising the steps of:
(a) blending arterolane maleate, piperaquine, at least one filler, at least one
superdisintegrant, at least one suspending agent with one or more
pharmaceutically acceptable excipients;
(b) optionally granulating the blend; and
(c) compressing the blend or granules into tablets.
In another general aspect there is provided a method of treatment of malaria by
administering a stable dispersible formulation comprising:
(a) arterolane maleate; and
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(b) piperaquine, wherein the formulation disintegrates within 3 minutes.
In another embodiment the malaria is caused by Plasmodium falciparum.
DETAILED DESCRIPTION OF THE INVENTION
The term "dispersible" as used herein is intended for dosage forms that completely
disperse in water in a short period of less than about three minutes to form a solution,
non-gritty suspension or slurry when placed either in water or in the oral cavity.
The term "homogeneous dispersion" as used herein means that the dispersion
produced upon contact with water or saliva ensures the uniformity of drug content for a
reasonable period of time.
The term "stable" as used herein refers to percentage degradation of both arterolane
maleate and piperaquine not more than 5 % of the initial value, after storage at 30°C
and 75% relative humidity, for a period of three years (36 months).
The term "arterolane maleate" as used herein means maleate salt of cis-adamantane-2spiro-
3'-8'-[[[(2'-amino-2'-methylpropyl)amino]carbonyl]methyl] 1', 2', 4'trioxaspiro[
4.5]decane. It further includes its individual enantiomers, diastereomers,
racemates and other isomers. Additionally it also includes all polymorphs and solvates,
such as hydrates and those formed with organic solvents. The present invention
comprises arterolane maleate in an amount of from about 2% to about 15% w/w of the
total formulation.
The term "piperaquine" includes its free base as well as pharmaceutically acceptable
salts thereof. Suitable salts of piperaquine include but are not limited to, acid addition
salts, such as those made with phosphoric, maleic, malonic, succinic, fumaric, malic,
tartaric, citric, methylsulfonic, hydrochloric, hydrobromic, hydroiodic, perchloric, sulfuric,
nitric, acetic, propionic, glycolic, lactic pyruvic, benzoic, carbonic cinnamic, mandelic,
methanesulfonic, ethanesulfonic, hydroxyethanesulfonic, benezenesulfonic, p-toluene
sulfonic, cyclohexanesulfamic, salicyclic, p-aminosalicylic, 2-phenoxybenzoic, and 2acetoxybenzoic
acid; salts made with saccharin. Preferably the salt is phosphoric acid,
forming piperaquine phosphate. It further includes all individual enantiomers,
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diastereomers, racemates, and other isomers of those compounds wherein such
structural variations are possible. Additionally it also includes all polymorphs and
solvates, such as hydrates and those formed with organic solvents, of these
compounds. The present invention comprises pipearquine as piperaquine phosphate in
an amount of from about 15% to about 40% w/w of the total formulation.
The present invention comprises arterolane maleate and piperaquine in a weight ratio
of about 1:1 to about 1:1O.
The present invention comprises arterolane maleate (equivalent to arterolane) in a dose
range of about 20 mg to about 80 mg and piperaquine in a dose range of about 150 mg
to about 200 mg.
The present invention comprises arterolane maleate (equivalent to arterolane) in a unit
dose of 25 mg, 37.5 mg and 50 mg and piperaquine in a unit dose of 187.5 mg.
The present invention provides a fixed dose combination of 37.5 mg of arterolane
maleate (equivalent to arterolane) and 187.5 mg of piperaquine for pediatrics with a
simple dosing regimen of once a day for three days.
The dose of arterolane maleate herein means dose equivalent to arterolane as free
base.
For pediatrics group of patients, the present invention provides a simple dosing regimen
based on the age group of patient. In the commercially available pediatric formulation
Le. Coartem® Dispersible tablets, the dosing regimen is based upon the body weight of
patient for which there is a requirement of a weighing machine before
dispensing/deciding the dosage regimen. This is not feasible every time.
The present invention provides a simplified dosing regimen based on the age group of
pediatrics such as for children of age:
- 6 months to less than 2 years, the dosing regimen is one tablet once a day for
three days;
- 2 years to less than 6 years, the dosing regimen is two tablets once a day for
three days; and
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- 6 years to less than 12 years, the dosing regimen is three tablets once a day for
three days.
The key features of dispersible tablets are fast absorption of water or complete wetting
of the tablets and disintegration of associated particles for fast dissolution. Improving
the wettability is a critical step as complete wetting on contacting the aqueous medium
ensures the formation of smooth suspension quickly after dispersion of the tablet.
The term "about", as used herein, when used along values assigned to certain
measurements and parameters means a variation of 10% from such values, or in case
of a range of values, means a 10% variation from both the lower and upper limits of
such ranges.
The formulation of the present invention comprises filler, superdisintrgrant, suspending
agent and one or more pharmaceutically acceptable excipients.
The formulation of the present invention comprises filler in order to give sufficient
material to tablet and facilitate the compression process used to make tablets. The filler
is selected from the group comprising microcrystalline cellulose, calcium disulfate,
calcium trisulfate, calcium carbonate, lactose monohydrate, lactose anhydrous,
sucrose, mannitol, sorbitol, calcium phosphate dibasic, calcium phosphate tribasic
kaolin, calcium silicate, maltodextrin, sugar alcohols such as xylitol, erythritol, sorbitol
and mannitol various starches and modified starches or mixtures thereof. The present
invention comprises filler in an amount of from about 30% to about 70% w/w of the total
formulation.
The superdisintegrant is selected from the group comprising croscarmellose sodium,
low-substituted hydroxypropylcellulose (L-HPC), sodium starch glycollate,
carboxymethyl cellulose, calcium carboxymethyl cellulose, cross-linked polyvinyl
pyrrolidone, natural, modified or pregelatinized starch, microcrystalline cellulose, gums,
alginic acid or mixtures thereof. The present invention comprises superdisintegrant in
an amount of from about 5% to about 15% w/w of the total formulation.
In the present invention filler and superdisintegrant are present in a weight ratio from
about 1:1 to about 1:20.
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Suspending agents help the drug to remain uniformly distributed in a suspension and
thus maintain content uniformity of the drug in suspension. These reduce the
sedimentation of the drug, thereby ensuring the uniformity of the dose. The suspending
agent is selected from the group comprising water-dispersible celluloses, propylene
glycol, polyethylene glycol, glycerin or mixtures thereof. In particular water-dispersible
celluloses are co-processed spray dried forms of microcrystalline cellulose and
carboxymethyl cellulose sodium. These have been marketed under the trade names
Avicel® RC-501 (containing 7.1 - 11.9% of sodium carboxymethyl cellulose), Avicel®
RC-581 (containing 8.3 - 13.8% of sodium carboxymethyl cellulose), Avicel® RC-591
(containing 8.3 - 13.8% of sodium carboxymethyl cellulose). Avicel® RC-581 and
Avicel® RC-591 differ only on the basis of viscosities. The present invention comprises
suspending agent in an amount of from about 1% to about 10% w/w of the total
formulation.
The term "pharmaceutically acceptable excipients" as used herein may include any
physiologically inert additive used in the pharmaceutical art of dispensing.
Pharmaceutically acceptable excipients may include lubricants, binders, sweetening
agents, flavoring agents and coloring agents.
The lubricant is selected from the group compnslng magnesium stearate, colloidal
silicon dioxide, stearic acid, calcium stearate, zinc stearate, sodium stearyl fumarate,
talc, hydrogenated castor oil, sucrose esters of fatty acid, microcrystalline wax, yellow
beeswax, white beeswax, silica gel or mixtures thereof.
The binder is selected from the group compnslng methyl cellulose, hydroxypropyl
cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl
cellulose, polyvinyl alcohol, microcrystalline cellulose, pullulan, pregelatinized starch,
agar, tragacanth, sodium alginate, propylene glycol, carboxyvinyl polymers or mixtures
thereof.
Sweetening agents, flavoring agents and mixtures thereof used in the present invention
are selected from those which are pharmaceutically acceptable, compatible with the
attributes of an oral dosage formulation. The sweetening agent is selected from the
group comprising aspartame, maltodextrin, cyclamate, acesulfame-K and its sodium
and calcium salts, saccharin and its various salts, sucrose or sucralose; sugar alcohols
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such as sorbitol, mannitol, xylitol, any natural or artificial sweetener such as glucose,
dextrose or fructose or mixtures thereof.
The flavoring agent is selected from the group comprising any natural or synthetic
flavoring liquid (such as volatile oils, synthetic flavor oils, flavoring aromatics, oils,
liquids, oleoresins and extracts derived from plants, leaves, flowers, fruits, stems and
combinations thereof, including, but not limited to, spearmint, peppermint, lemon,
caramel, banana, vanilla, orange, grape, lime or grapefruit citric oils or apple, pear,
peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, or other mint or
fruit flavor essences), an aldehyde or ester (such as benzaldehyde (cherry, almond),
citral, a-citral (lemon, lime), neral, beta-citraI (lemon, lime), decanal (orange, lemon),
aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits),
tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruit), 2-dodedenal (citrus,
mandarin) or mixtures thereof.
Examples of coloring agents include, but are not limited to, any pharmaceutically
acceptable natural or synthetic dyes. such as Red ferric oxide, titanium dioxide, Lake of
Tartrazine, Lake of Quinoline Yellow, Lake of Sunset Yellow and Lake of Erythrosine,
Lack of Carmosine Ponceau, Allura Red or mixtures thereof.
In another embodiment, the formulation of the present invention may be selected from
group consisting of tablets, pellets, pills, granules and powder. Particularly, the
formulation is a tablet.
Pellets, pills, granules and powder in form of a simple mixture can be filled into sachets
that can be emptied into water.
Dispersible tablets are intended to be dispersed in water or milk prior to administration,
resulting in a homogenous dispersion. Further these can also be kept in mouth to form
dispersion with the help of saliva.
In another embodiment, the dispersible tablet may be further coated with at least one
functional and/or non-functional layers comprising film-forming polymers, and other
coating additives.
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Examples of film-forming polymers include but not limited to cellulose derivatives such
as ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose,
methylcellulose, carboxymethylcellulose, hydroxymethylcellulose,
hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate,
cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene
glycol; methacrylic acid polymers such as Eudragit® RL and RS; or mixtures thereof.
Alternatively, commercially available coating compositions comprising film-forming
polymers marketed under various trade names, such as Opadry® may also be used for
coating.
The coating additives comprise one or more of plasticizers, glidants or flow regulators,
opacifiers and lubricants.
In another embodiment, the stable dispersible formulation of arterolane maleate and
piperaquine is prepared by a dry process.
In another embodiment, the dry process is selected from dry granulation or direct
compression.
In another embodiment, the dry granulation is carried out by using slugs, roller
compactor or chilsonator.
In yet another embodiment, tablets prepared by any of the above described processes
may further be coated with film forming polymers and one or more coating additives,
using techniques well known in the art such as spray coating in a conventional coating
pan or a fluidized bed processor; or dip coating. Alternatively, coating can also be
performed using a hot melt technique.
The coating layers over the tablet may be applied as a solution/dispersion of coating
components in a suitable solvent. Examples of solvents used for preparing a
solution/dispersion of the coating ingredients include methyl alcohol, ethyl alcohol,
isopropyl alcohol, n-butyl alcohol, acetone, acetonitrile, chloroform, methylene chloride,
water and the like, or mixtures thereof.
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The invention is further illustrated by the following examples, which is for illustrative
purpose only and should not be construed as limiting the scope of the invention in any
way.
Examples
Quantity %w/w
Ingredients Example 1 Example 2 Example 3
Arterolane maleate 4.32 6.08 7.62
(equivalent to
arterolane)
Piperaquine phosphate 25.00 23.44 22.06
Microcrystalline 51.08 51.38 51.66
cellulose
(Avicel@ PH 102)
Microcrystalline 2.00 2.00 2.00
cellulose and sodium
sodium carboxymethyl
cellulose
(Avicel@ RC 591)
Croscarmellose 6.50 6.50 6.50
sodium
Aspartame 8.00 7.50 7.06
Orange Captarome 1.00 1.00 1.00
Vanilla 0.10 0.10 0.10
Colloidal silicon dioxide 0.50 0.50 0.50
Magnesium stearate 1.50 1.50 1.50
Total weight 750.00 mg 800.00 mg 850.00 mg
Procedure:
1. Arterolane maleate, microcrystalline cellulose, microcrystalline cellulose and
sodium carboxymethyl cellulose, croscarmellose sodium and colloidal silicon
dioxide were sifted through a sieve # 36 BSS and piperaquine phosphate was
sifted through a sieve # 18 BSS.
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2. Aspartame, orange captarome and vanilla flavor were sifted through a sieve # 60
BSS.
3. Materials from steps 1 and 2 were blended and mixed for 30 minutes.
4. The blend of step 3 was lubricated with magnesium stearate.
5. The lubricated blend from step 4 was compressed using suitable size punches to
obtain compressed tablets.
Disintegration data
Three batches of six tablets each prepared according to Example 2 were tested for
disintegration using BP Disintegration apparatus. The results of disintegration are
presented in Table 1.
Table 1: Disintegration Times (Example 2)
Batch Tablet 1 Tablet 2 Tablet 3 Tablet 4 Tablet 5 Tablet 6
No.
1 1 minute 1 minute 1 minute 1 minute 1 minute 1 minute
2 1 minute 1 minute 1 minute 1 minute 1 minute 1 minute
3 Less than Less than Less than Less than Less than Less than
30 30 30 30 30 30 seconds
seconds seconds seconds seconds seconds
In-vitro Dissolution data
In-vitro drug release from the tablets prepared according to Example 2, was determined
by dissolution for arterolane maleate in USP type II apparatus at 75 rpm, in 900ml of pH
4.5 acetate buffer with 2% tween 80 for 45 minutes. Similarly in-vitro drug release from
the tablets prepared according to Example 2, was determined by dissolution for
piperaquine phosphate in USP type II apparatus at 75 rpm, in 900ml of 0.01 N
hydrochloride for 45 minutes. The results of the dissolution study are presented in
Table 2.
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Table 2: In-vitro drug release (%w/w) at 45 minutes
Time Arterolane released Piperaquine released
(%w/w) (%w/w)
45 minutes 99 98
Stability data
The tablets prepared according to Example 2 were stored at 30°C ± 2°C and 75% ± 5%
relative humidity for a period of 36 months, and analyzed for arterolane and piperaquine
contents and related substances using validated in house HPLC analytical method. The
results of the analysis are represented in Tables 3 and 4.
Table 3: Results of the Stability Study for Arterolane maleate
Conditions Assay Related substances
30oC175% RH (Arterolane) (%w/w)
Initial 37.45. 0.29
1 M 37.94 0.34
2M 37.25 0.41
3M 37.35 0.51
6M 37.80 0.57
9M 37.21 0.55
12 M 37.07 0.63
18 M 36.97 0.72
24M 36.31 0.809
36 M 36.41 0.894
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Table 4: Results of the Stability Study for Piperaquine phosphate
Conditions Assay Related substances
30oC/75% RH (Piperaquine) (%w/w)
Initial 187.70 0.89
1 M - -
2M - -
3M 190.91 0.93
6M 187.51 0.89
9M 191.99 0.89
12 M 191.59 0.92
18 M 186.93 0.93
24 M 193.18 0.983
36 M 187.27 1.067

WE CLAIM:
1. A stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the formulation disintegrates within 3 minutes.
2. The stable dispersible formulation according to claim 1, wherein arterolane
maleate and piperaquine are present in a weight ratio from about 1:1 to about
1:10.
3. The stable dispersible formulation according to claim 1, wherein arterolane
maleate is present in a dose range of about 20 mg to about 80 mg and
piperaquine is present in a dose range of about 150 mg to about 200 mg.
4. The stable dispersible formulation according to claim 1, wherein the formulation
is prepared by a dry process.
5. A stable dispersible formulation comprising:
(a) arterolane maleate;
(b) piperaquine;
(c) one or more filler(s);
(d) one or more superdisintegrant(s), and
(e) one or more suspending agent(s), wherein the formulation disintegrates
within 3 minutes.
6. The stable dispersible formulation according to claim 5, wherein the formulation
comprises:
(a) about 2% to about 15% by weight of arterolane maleate;
(b) about 15% to about 40% by weight of piperaquine;
(c) about 30% to about 70% by weight of a filler;
(d) about 5% to about 15% by weight of a superdisintegrant; and
(e) about 1% to about 10% by weight of a suspending agent.
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7. The stable dispersible formulation according to claim 5, wherein the filler is
selected from the group comprising microcrystalline cellulose, calcium disulfate,
calcium trisuIfate, calcium carbonate, lactose monohydrate, lactose anhydrous,
sucrose, mannitol, sorbitol, calcium phosphate dibasic, calcium phosphate
tribasic kaolin, calcium silicate, maltodextrin, sugar alcohols such as xylitol,
erythritol, sorbitol and mannitol various starches and modified starches or
mixtures thereof.
8. The stable dispersible formulation according to claim 5, wherein the
superdisintegrant is selected from group comprising croscarmellose sodium, lowsubstituted
hydroxypropylcellulose (L-HPC), sodium starch glycollate,
carboxymethyl cellulose, calcium carboxymethyl cellulose, cross-linked polyvinyl
pyrrolidone natural, modified or pregelatinized starch, microcrystalline cellulose,
gums, alginic acid or mixtures thereof.
9. The stable dispersible formulation according to claim 5, wherein the suspending
agent is selected from group comprising water-dispersible celluloses, propylene
glycol, polyethylene glycol, glycerin or mixtures thereof.
10.The stable dispersible formulation according to claims 1 or 5, wherein the
formulation is selected from group consisting of tablets, pellets, pills, granules
and powder.
11.The stable dispersible formulation according to claim 10, wherein the formulation
is a tablet.
12.The stable dispersible formulation according to preceding claims, wherein the
formulation further comprises pharmaceutically acceptable excipients selected
from the group consisting of lubricants, binders, sweetening agents, flavoring
agents and coloring agents.
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13.The stable dispersible formulation according to claim 5, wherein the formulation
is prepared by a process comprising the steps of:
(a) blending arterolane maleate, piperaquine, at least one filler, at least one
superdisintegrant, at least one suspending agent with one or more
pharmaceutically acceptable excipients; and
(b) directly compressing the blend into tablets.
14.A stable dispersible formulation comprising:
(a) arterolane maleate; and
(b) piperaquine, wherein the dosing regimen for pediatrics is once daily for three
days.
15. The stable dispersible formulation according to the preceding claims, wherein
the said formulation is used for the treatment of malaria.
16. An oral dispersible formulation of arterolane maleate and piperaquine and
process of preparation thereof, as described and illustrated in the examples
herein.