FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"Stable antimalarial formulations"
2. APPLICANT (S)
(a) NAME: McW Healthcare Pvt. Ltd.
(b) NATIONALITY: An Indian Company incorporated under the
Indian Companies ACT, 1956
(c) ADDRESS: 286, Sector E, Industrial area, Sanwer raod, Indore, Madhya Pradesh, 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 of the invention:
The present invention relates to stable solid oral pharmaceutical compositions useful for the treatment of drug resistant malaria comprising a therapeutically effective amount of an anti malarial agent selected from Quinine, Mefloquine, Halofentrine, Chloroquine, Primaquine, their derivative or pharmaceutically acceptable salt., wherein the said solid dosage form is characterized by being enteric coated tablet thus resistant to gastric juices and thereby improving therapeutic efficacy. The invention further relates to liquid oral formulation in the form of a suspension to achieve improved bioavailability and therapeutic efficacy of the active. Further the invention relates to process of preparation of the said formulations.
Background of Invention:
Antimalarial drugs were first discovered in the seventeenth century, two and one-half centuries before the causative agent of malaria was identified. Quinine was the first antimalarial drug derived from the bark of cinchona tree. It was none other drug but quinine, which helped to shape today's world by enabling explorers and colonists from Europe to survive in tropical countries and to build their colonial empires despite lethal tropical malaria. When physicians were asked to choose the ten most important drugs being used in medicine in 1945, quinine and quinacrine were preceded only by penicillin, sulfonamides and blood derivatives. The antimalarial activity of quinoline as antimalarial drug can be attributed to its interference with hemoglobin digestion in the blood stages of the malaria parasite's life cycle. The parasite degrades the host hemoglobin, in an acidic food vacuole, to generate amino acids for its own protein synthesis, and producing free heme and reactive oxygen species as toxic by-products. The heme moieties are neutralized by polymerization, and this process is thought to be the biochemical target for antimalarial drugs. Although antimalarial drugs were developed primarily to treat malaria, and never lost their place in treating this life-threatening disease (still a major cause of infant death in the tropics), they are also beneficial for many dermatological, immunological, and rheumatological diseases, for which they are mostly used today in the Western world.
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Multi-drug-resistance in P. falciparum malaria and high level of P. vivax resistant strains are posing a major threat to the countries in South-east Asia, Africa and Southern America. Most seriously affected areas include Thai-Myanmar Burmese border, where resistance to nearly all available drugs (Chlorquine, Sulfadoxine-Pyrimethamine, Mefloquine, Quinine) is already established, (WHO Report on Infectious Diseases, 1999, WHO/CDS/99.1).
A pharmaceutically acceptable salt of quinine, for example, the acid addition salt with one or two equivalents of a monobasic inorganic or organic acid or the acid addition salt with a dibasic inorganic or organic acid such as the hydrochloride, dihydrochloride, hydrogensulphate or sulphate salt, carbonate or hydrogen carbonate are widely known antimalarial agent.
US2006263427 discloses controlled-release quinine formulations and the method of preparation comprising quinine salts include quinine sulfate, quinine hydrochloride, quinine dihydrochloride, and hydrates or solvates along with acrylic or acrylate polymer, an acrylic or acrylate copolymer, an alkylcellulose, a shellac, a zein, a hydrogenated a polyalkylene glycol, a hydroxyalkylcellulose, a crosslinked hydroxyalkylcellulose, a carboxyalkylcellulose, a crosslinked carboxyalkylcellulose, a hydroxyalkyl alkylcellulose, a carboxyalkyl starch, a polyvinyl alcohol, etc as release-retarding matrix formulated into solid or liquid composition for oral administration or a sterile aqueous or non- aqueous solution for parenteral administration.
Many antimalarial drugs such as Quinine, Meflaquine, Halofentrine, Primaquine and pyronaridine, their derivatives and salts are available in the market, alone or in combination in the various dosage forms. The above drugs degrade in the stomach due to secretion of gastric juice (pH =1-2), thereby reducing the bioavailability of the drug, which is the major disadvantage of the orally administrated formulations.
For the foregoing reasons, there is a need of a pH independent stable formulation which can withstand variation in pH in the intestine, duodenum, jejunum and ileum, without affecting therapeutic effectiveness of the antimalarial agent.
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In view of aforementioned prior art preparations it is obvious that there still exists a need for improved formulation of quinine sulphate which are safe, stable, simple to manufacture and cost effective. Therefore, it is an object of the present invention to provide an enteric coated tablet to avoid the degradation of the active in gastric pH, thus releasing the active in intestine thereby improving the bioavailability and therapeutic efficacy of the drug.
Object of Invention:
The main object of the invention is to provide stable antimalarial formulations useful for the treatment of drug resistant malaria comprising Quinine sulphate formulated as enteric coated tablets and suspensions and process for preparation thereof.
Another object of present invention is to provide a composition which is highly effective against drug resistant malaria and a convenient dosage form for adult, children and infants.
Summary of Invention:
The present invention provides the stable formulations of Quinine sulphate in the form of enteric coated tablets and suspensions useful for treatment of malaria i.e. P.falciparum and P.vivax. The coated tablet of invention includes a tablet core and a layer coated on the core, which consists of at least one coating polymer; a second coating layer over an inner coating layer form an enteric coat containing a polymer which is preferably the same polymer that is used in the inner coating layer. Optionally an outer protective coating layer, disposed over second coating layer formed of at least one coating polymer and excipients with same composition, but in different ratio.
In preferred aspect, the coated tablet of the invention will include a tablet core formulated along with one or more pharmaceutically acceptable excipients such as one or more bulking agents or fillers and optionally includes one or more binders, one or more disintegrators and one or more tablet lubricants or mixtures thereof. The said formulation
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can be administered through the oral route in different dosage forms to children, adult and infant for complete elimination of malarial infection.
In accordance with the present invention, a method is provided for preparing the coated tablet of the invention, which includes the following steps:
a) preparing a tablet core comprising the active ingredient along with pharmaceutically
acceptable excipients;
b) compressing the above mixture by using the specific size of punches to get tablets of
suitable size;
c) coating the tablet core with the inner seal coating layer which includes at least one
coating polymer;
d) drying the tablet core to form an inner seal coating thereon;
e) coating the aforesaid coated tablet with second protective layer which includes at least one coating polymer.
Detailed description of invention:
Quinine Sulphate is a rapidly acting blood schizontocide with activity against Plasmodium falcipuram, P. vivax, P. ovale and P. malaria, although it's gametocytic activity is restricted to P.malaria and P.vivax only. In one of the embodiment, the pharmaceutical formulation of the present invention is safe against sexual stage of parasite selected form P vivax, P ovale and P malaria.
The precise mechanism of action of quinine in controling malaria has not been determined but, it may be attributed to its ability to concentrate in parasitic acid vesicles causing an elevation of pH and thereby disrupting intracellular activity.
Quinine increases the refractory period of skeletal muscle by direct action on the muscle fibre thereby diminishing the response to titanic stimulation. It also decreases the excitability of the motor endplate region, reducing the responses to repetitive nerve stimulation and to acetylcholine as well.
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In accordance with the present invention, the route of administration is preferably through oral dosage forms such as tablets, capsules and suspensions or optionally injectable forms.
In yet another embodiment, the pharmaceutical formulation of the present invention provides extended bio availability because of longer T1/2 (plasma half life) and this formulation is administrated orally to the adults in the form of tablets and suspensions and to the children in the form of suspensions for longer periods such as once or twice a day for a week.
In one more preferred embodiment, the present invention provides the process for the preparation of a pharmaceutical composition to control malarial parasite completely as the said formulation is effective against gastric juice because of the biconvex enteric coated oral tablet forms.
The present ivention describes tablet core which may be in the form of tablet, bead, beadlet or pill, collectively referred to as tablet core.
The tablet core in the coated tablet of the present invention preferably contains at least one bulking agent or filler and optionally at least one binder, disintegrator and lubricant wherein bulking agent or filler present in core tablet is in the range of 10 to 90 % by weight, preferably 10 to 80 % by weight.
The tablet core in the present formulation can be prepared by conventional processes such as wet granulation, dry granulation, direct blending or any other pharmaceutically acceptable process, not specific to unit dosage forms.
In accordance with the present invention, a preferred method provided for preparing the tablet core employed in the coated tablet of the invention includes the steps of blending of the granules with the one or more excipients such as a bulking agent, and optionally binders, disintegranls, lubricants are added preferably to facilitate tablet formation.
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The binders employed in the formulation are present in the range of 1 to 20 % by weight preferably in the range of 1 to 10 %, disintegrants are present in the range of 1 to 20 % by weight preferably 0.5 to 10 % by weight and lubricants are present in the range of 0 to 5 % preferably by 0.2 to 2 % by weight. All of the above % by weight are based on the weight of tablet core.
The bulking agents or fillers employed are in the range of 1 to 95 % as per the weight of tablet core, preferably from 10 to 85%. Examples of the pharmaceutical^ acceptable bulking agents or fillers includes, but not limited to, starch, talc cellulose derivatives, lactose, sucrose, starch, pregelatinised starch, dextrose, mannitol, fructose, xylitol, sorbitol, corn starch, modified corn starch or inorganic salts such as calcium carbonate, calcium phospate, calcium sulphate, dextrin, maltodextrine, compressible sugar and other bulking agent or fillers and a mixture of two or more bulking agents thereof, preferably purified talc and maize starch or Dicalcium phosphate.
Binders impart cohesive qualities to tablet and ensure that the tablet remains intact after compaction The Binders employed in the present formulation are in the range of 0 to 30 % by weight of tablet core, preferably in the range of 1 to 20 % by weight of tablet core. Examples of pharmaceutically suitable binders includes, but are not limited to, Hydroxy propyl methyl cellulose, corn starch, pregelatinised strach, modified starch, polyvinyl pyrrolidone (molecular weight ranging from 5000 Da to 1000000 Da, preferably about 40,000 Da), lactose, gum acacia, ethyl cellulose, cellulose acetate as well as wax binder such as caurnaba wax as well as other conventional binding agent and mixture of two or more, preferably Polyvinyl pyrrolidon.
The lubricants employed in the present formulation are in the range of 1 to 20 % preferably from 1 to 10% by the weight of tablet core. Examples of pharmaceutically acceptable tableting lubricants includes, but are not limited to, magnesium stearate, zinc stearate,calcium stearate, talc, stearic acid, palmitic acid or other known tableting lubricant and /or mixture of two or more lubricant thereof , preferably magnesium stearate.
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Disintegrants are used to facilitate tablet disintegration or "breakup" after administration. The disintegrant employed in the present formulation are in the range of 0 to 20% by weight of core composition. Examples of pharmaceutically acceptable disintegradent include, but are not limited to crosspovidone, starch, croscarmellose sodium, potato starch, pregelatinised starch,corn starch, sodiun starch glycolate, low substituted hydroxy propyl cellulose or other disintegradents preferably, croscarmellose sodium.
The inner seal coating layer formulation (also referred to as first coating layer) includes about 90 % polymer based on the weight of the inner seal coating layer. The present formulation contains at least one polymer having a cellulose base. Suitable solvents used for coating are selected form a group of organic solvents such as isopropyl alcohol and methylene dichloride which can be easily removed by drying.
An inner seal coating polymer comprises at least one cellulose based polymer and a second protective coating layer comprises preferably similar or optionally different polymer.
The coating layers are applied to the tablet core preferably by spray coating on to the tablet core. The coated tablets of the invention may be prepared preferably using perforated pan coaters. Fluid bed coating and spray coating may be used as well.
The coating layer polymers employed in the present invention such as hydroxy propyl methyl cellulose, ethyl cellulose, polyvinyl alcohol or hydroxy propyl cellulose or any other coating polymer known in the art or a mixture of two or more polymers. Most preferred polymers are hydroxy propyl methyl cellulose and ethyl cellulose. The coating layer may optionally include plasticizers such as diethyl phthalate, tributyl sebacate or poly ethylene glycol, preferably diethyl phthalate and anti adherent or glidant such as Talc and opacifying agent such as titanium dioxide, if desired.
The second coating layer may be similar to that of the first coating layer. The polymer used for enteric coating may be the same as per first coating or cellulose acetate phthalate or the like, or combination thereof, preferably includes cellulose acetate phthalate.
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In yet another embodiment, the present invention describes an oral suspension of quinine sulphate and a method of preparation comprising therapeutically effective amount of Quinine sulphate along with the pharmaceutically acceptable excipients.
The oral suspension according to the invention, in addition contains, at least one agent chosen from an alkalinizing agent, a viscosity agent, a glidant, a flavoring, a preservative, a coloring, a lubricant and a sweetener.
The oral pharmaceutical suspension according to the invention comprises a liquid phase which is aqueous or consists of a mixture of water with a co-solvent, for example oil, propylene glycol, glycerin or a solution of sorbitol, preferably DM water.
The viscosity agent is chosen from pharmaceutically acceptable viscosity agents, for example xanthan gum, hydroxypropylmethyl cellulose, methyl cellulose, carrageenan, carboxy methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone and carbomers, preferably a mixture of Digluco diglycero poly glyceride and carbopol is used. The viscosity agent represents 1 to 50%, preferably 1 to20%, by weight relative to the weight of the suspension.
The glidant is selected from the group consisting of colloidal silicon dioxide, talc, fumed silica, magnesium stearate, calcium stearate, magnesium trisilicate, powdered cellulose, starch, tri basic calcium phosphate, and mixtures thereof, preferably of colloidal silicon dioxide is used in the range of 1 to 15 %
Suitable alkalinizing agent for a liquid oral suspension according to the invention are physiologically acceptable aqueous buffer systems with alkaline pH in the range from 10-10.4 or mixtures thereof with other physiologically acceptable liquids, preferably Sodium hydroxide in water used in the range of 1to 10%.
The preservative or the mixture of preservatives makes it possible to maintain the microbiological integrity of the suspension and to satisfy the regulatory requirements relating to the enumeration of total and specific microorganisms and to the study of efficacy of the preservatives. The preservative represents 1 to 30 %, preferably 1 to 10 %, by weight relative to the weight of the suspension.
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A mixture of preservatives is preferably used so as to obtain a synergy of antibacterial effects. At least one of the preservatives is selected from the esters of parabens or the corresponding salts, preferably sodium salt of Nipagin and Nipasol along with Bronopal.
The pharmaceutically acceptable taste masking agent includes Indion 234 to taste masking the bitterness of quinine salts present in the range of 20 %
The selection of the sweetener is based on its higher sweetening power than sucrose. Examples of pharmaceutically acceptable sweetener include, but are not limited to aspartame, saccharin, sodium cyclamate and mixtures thereof, preferably aspartame is used.
The flavoring agent may be of natural or synthetic origin. It represents 1 to 20 % by weight relative to the weight of the suspension, preferably orange flavor is used.
Likewise, the coloring agent may be selected form a group of a natural or synthetic pigment, depending on the basis of selection of the suspension flavor. For example, in case of an orange flavor, Sunset yellow is chosen preferably.
The process for the preperation of enteric coated tablet and suspension is summarized below:
For tablets:
Quinine sulphate and starch are sifted and mixed, binder solution containing polyvinyl pyrolidone in isopropyl alcohol is added to it and the size of granules are reduced using mesh by the method known in the art. Dry granuales are sifted and lubricated using purified talc, magnesium sterate, carmellose sodium, sodium starch glycolate or any suitable pharmaceutically acceptable lubricant. The resulting mixture is compressed by using the specific size of punches to get tablets of suitable size.
For Suspensions:
Indion and Quinine sulphate is taken into a vessel and water is added with constant stirring to get a desired solution. The above solution is homogenized with Digluco diglycero poly glyceride and carbopol is added with stirring and the desired pH was
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attained using sodium hydroxide. Nipagin sodium, Nipasol sodium , sodium chloride and
bronopol dissolved in DM water is added to the above mixture.
Further, a solution of Aspartame in DM water and Collidal silicon dioxide is added to
obtain desired suspension. A clear solution of Sunset yellow colour in DM water is added
to the above mixture followed by addition of glycerin slowly with stirring.
Finally a solution of menthol with orange flavour is added with stirring to make up the
volume of a desired homogeneous suspension.
The invention is more specifically explained by following examples. However, it should be understood that the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the present invention includes the following examples and further can be modified and altered within the technical concept of the present invention.
Examples:
The present invention is further illustrated, but not limited to the following examples. The examples for the different strengths i.e. 100 mg, 300 mg and 600 mg are given below:
Example-1: Enteric coated tablets 100 mg.

S.No. Ingredients Qty in Milligram.
01 Qunine Sulphate 100 mg
02 Maize starch 15 mg
03 Dicalcium Phosphate 50 mg
04 Polyvinyl pyrrolidon 5mg
05 Sodium starch glycolate 5mg
06 Talcum 5mg
07 Magnesium stearate 5mg
08 Cross Carmellose sodium 5 mg
Total 190 mg
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Process:
1. Quinine Sulphate powder 60.00 kg and maize starch 2.300 kg is passed through 30 mesh. Collect the passing material is collected and loaded to mixer for 10 minutes to get a desired mixture.
2. Polyvinyl pyrrolidone -K. 2.500 kg is dissolved into 32.00 Ltr. Isopropyl alcohol with continuous stirring to obtain a homogeneous solution for binding.
3. Binder solution is added slowly and gradually to a shifting material in mass mixer to obtain a damp cohesive mass.
4. The above damp cohesive mass is sifted through 4 mm mesh of granulator and the wet granules are collected.
5. Wet granules are loaded into F.B.D bowl and dried without starting heater of F.B.D for about 10 minutes so as to achieve desired moisture content.

6. Dried granules are passed through 14 mesh. The oversized granuleswere passed through 3 mm mesh by using granulator. The sifted granules were collected into vessel and loaded into mass mixer for further processing.
7. Purified talc 2.00 kg, magnesium stearate 2.00 kg ,Croscarmellose sodium 0.700 kg and sodium starch glycolate 0.500 kg are sifted through a 40 mesh and the sifted material is collected into a clean container.
8. Sifted lubricants are loaded into the mass mixer and mixed for 10 minutes to get desired lubrication. Lubricated granules are unloaded into a clean vessel for further processing.
9. By using desired size of dies and punches, the lubricated material is compressed to get tablets of desired specification:
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S.N. Parameter Specification
01 Upper punches Round concave
02 Lower punches Round concave
03 Punch size 13.45 mm Round
04 Tablet description Uncoated white round tablet
05 Disintegration time and limit NMT15Min.
06 Hardness 6 Kg/cm2 ± 2 kg/cm2
07 Standard avg.wt. of one tablet and limit 190mg(±4.5%)
08 Thickness 4.20 mm (±0.5 mm)
09 Friability NMT 1%
A tablet core composition for strength 100 mg of Quinine sulphate (Core tablet weight = 190 mg)

Excepients % w.r.t. weight of tablet Core Quantity of excipients (in mg)
Polyvinyl pyrrolidon 1 to 20 % . 0.5 mg-10.5 mg
Purified talc 1 to 20 % 0.5 mg-10.5 mg.
Magnesium sterate 1 to 20 % 0.5 mg-10.5 mg.
Cross carmellose sodium 1 to 20 % 0.5 mg-10.5 mg.
Sodium starch glycolate 1 to 20 % 0.5 mg-10.5 mg.
Maize starch 1 to 20 % 1.9 mg- 38 mg.
Dicalcium Phosphate 1 to 50 % 1.9 mg - 95 mg.
Preparation of Coating solution (Seal coat):
5.00 kg of isopropyl alcohol is added to 0.700 kg of hydroxy propyl methyl cellulose in a
clean container Diehtyl phthalate; ethyl cellulose, purified talc and titanium dioxide are
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added to the above mixture with continuous stirring and followed by slow and gradual addition of 10.00 kg of methylene di chloride.

Seal coating layer % w.r.t Weight of tablet Quantity of excipients
core (in mg)
Cellulose Coating polymer,plasticizer, gladient, andopacifying agent. 0.1 to 10% 0.19-1.9 mg.
Preparation of Enteric Coating solution:
44.00 kg of acetone is added to in 3.6 kg previously well mixed enteric coating materials such as, Diethyl phthalate, cellulose acetate phthalate, purified talc and titanium dioxide to get desired coating solution using coating pan with the method known in art.

Outer protective layer(Enteric coating layer) % w.r.t Weight of tablet core Quantity of excipients (in mg)
Coating polymer, plasticizer, and opacifying agent. 1 to 20 % 0.52 mg -10.4 mg.
Example-2: Oral suspention:
Step -1 Preparation of active (I):
To 70 ltr of DM water, Indion 234 15.0 Kg is added slowly with stirring keeping the vessel with stirring mode for 30 minutes. Qunine sulphate 7.5 kg was added to the above mixture slowly and gradually allowing constant stirring. 0.240 kg of tween 80 is added slowly and gradually to the vessel, with continuous stirring for a 6 hrs.
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Step -2 Preparation of base (II):
Setting S S vessel below homogenizer, 15.0 ltr DM water is added into the vessel and
35.0 kg of Digluco diglycero poly glyceroid is added into the vessel, slowly and gradually
with stirring for 5 minutes.
1.00 kg of carbapol 934 is added, into the vessel slowly and with gradual stirring sodium
hydroxide (0.680 kg in 10 Itr water) is added slowly and gradually to ensure the pH of
base solution in between 10-10.5.
Step -3
The mixtures of step 11 and step 1 are mixed slowly and gradually with continuous
stirring.
Nipagin sodium 0.480 kg, Nipasol sodium 0.240 kg, Sodium chloride 0.960 kg and
Bronopol 0.024 kg were dissolved into 5 litre of DM water with continuous stirring to get
a desired homogeneous solution. This mixture is added to the above blend with constant
stirring.
Aspartame 0.300 kg is dissolved into 2 Ltr of DM water and added to the above mixture.
0.05kg of Colloidal silicon dioxide is added slowly into the above mixture with constant
stirring.
0.015 kg of Sunset yellow is dissolved into the 500 ml of DM water and added to the
above mixture with stirring the whole bulk for 30 minutes.
The whole bulk is colloided slowly and gradually using colloidal mill. The colloidal bulk
was collected in suitable SS container and made to stand without disturbing for 8 hrs.
7.00 kg of glycerin is added into the bulk with constant stirring. 0.038 kg of menthol is
mixed with 1.5 ltr. of orange flavor and added to bulk with constant stirring .
0.500 Itr of mixed fruit flavor is added to the bulk with constant stirring and finally to
make up the volume, DM water is added by stirring it for 30 minutes.
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We claim:
1) A stable solid oral pharmaceutical composition useful for the treatment of drug resistant malaria comprising a therapeutically effective amount of an anti malarial agent selected from Quinine, Mefloquine, Halofentrine, Chloroquine, Primaquine, their derivative or pharmaceutically acceptable salt in., wherein the said solid dosage form is characterized by being enteric coated tablet thus resistant to gastric juices and thereby improving therapeutic efficacy and process thereof.
2) The stable composition as claimed in claim 1, wherein the said anti malarial agent is Quinine, its derivative or pharmaceutically acceptable salt, preferably Quinine sulphate.
3) The solid dosage form as claimed in claim 1, wherein the enteric coated tablet of Quinine sulphate comprising of a tablet core surrounded by inner seal coated layer and outer protective enteric coated layer and optionally an additional protective layer.
4) The solid dosage form as claimed in claim 1, wherein an enteric coated tablet comprises:
(i) a tablet core consisting essentially of about 100 milligrams-600 milligrams of Quinine
sulphate as the principal active ingredient admixed with pharmaceutically acceptable
excipients:
(ii) a seal coat comprising up to about 0.1 to 10 % based on the weight of the core;
(iii) an enteric coat consisting about 1 to 20 % by weight based on the weight of the core;
(iv) a protective coat consisting essentially of about 1.5% to about 5% by weight based on
the weight of the core.
5) The solid dosage form as claimed in claim 3, wherein the pharmaceutically acceptable excipients comprising the tablet core are selected from cellulose based polymers, fillers, binders, lubricants, and disintegrants or optionally other pharmaceutically acceptable excipients.
6) The solid dosage form as claimed in claim 3, wherein the said tablet core comprising at least one filler like purified talc, at least one binder like polyvinyl pyrrolidon, at least
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one lubricant like magnesium stearate, at least one disintigrant like cross carmellose sodium or optionally other pharmaceutically acceptable excipients.
7) The solid dosage form as claimed in claim 3, wherein the inner seal coating layer comprising at least one cellulose based polymer and second protective enteric coating layer comprising the same or optionally comprises a different polymer.
8) The solid dosage form as claimed in claim 3, wherein inner seal coat layer comprises at least one cellulose based polymer with at least one plasticizer, glidant and opacifying agent
9) The solid dosage form as claimed in claim 3, wherein outer protective enteric coat layer comprises a cellulose based polymer with at least one plasticizer and opacifying agent.

10) The solid dosage form as claimed in claim 5, wherein a cellulose based polymer is selected from the group consisting of Hydroxy propyl methyl cellulose and ethyl cellulose present in the range of 1 to 20 % by weight relative to the weight of the core.
11) The solid dosage form as claimed in claim 5, wherein the plasticizer is selected from the group consisting of diethyl phthalate, tributyl sebacate or poly ethylene glycol, preferably diethyl phthalate prresent in the range of 1 to 50 % by weight relative to the weight of the core.
12) The solid dosage form as claimed in claim 1, wherein the enteric coated tablet of Quinine sulphate is prepared by a process comprising the steps of:
a) preparing a tablet core comprising the active ingredient along with pharmaceutically
acceptable excipients;
b) compressing the above mixture by using the specific size of punches to get tablets of
suitable size;
c) coating the tablet core with the inner seal coating layer which includes at least one
coating polymer;
d) drying the tablet core to form an inner seal coating thereon and
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e) coating the aforesaid coated tablet with enteric coated layer which includes at least one coating polymer.
13) Stable pharmaceutical formulations as claimed in any of the preceding claims 1 to 12, their process of preparation as substantially described herein with reference to the foregoing examples.
Dated this 12th day of March 2007
Dr. Gopakumar G. Nair
Agent for the Applicant
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Abstract:
Disclosed herein stable solid oral pharmaceutical compositions useful for the treatment of drug resistant malaria comprising a therapeutically effective amount of an anti malarial agent selected from Quinine, Mefloquine, Halofentrine, Chloroquine, Primaquine, their derivative or pharmaceutically acceptable salt wherein the said solid dosage form is characterized by being enteric coated tablet thus resistant to gastric juices and thereby improving therapeutic efficacy. The invention further discloses liquid oral formulation in the form of a suspension to achieve improved bioavailability and therapeutic efficacy of the active. The invention also discloses processes of preparation of the said formulations.
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