FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL COMPOSITION OF CINACALCET"
2. APPLICANT:
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Companies Act, 1956
(c) ADDRESS: Mumbai Central, Mumbai - 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 formed.

FIELD OF INVENTION:
The present invention relates to a pharmaceutical composition comprising cinacalcet, a process for preparing such a pharmaceutical composition, and use of the said pharmaceutical composition. The pharmaceutical composition of the present invention specifically relates to liquid and semi-solid compositions of cinacalcet or compositions wherein such liquid and semi-solid compositions are encapsulated in soft or hard gelatin capsules.
BACKGROUND AND PRIOR ART:
Active pharmaceutical ingredients (APIs) are commonly classified according to the Biopharmaceutics Classification System (BCS) and as per this classification system, almost more than 35% of the drugs that are commonly prescribed are considered to be poorly water-soluble.
In such cases, where the API's are poorly water-soluble, conventional formulation strategies are no longer adequate or useful to achieve the acceptable solubility and the bioavailability.
One example of such poorly water-soluble drugs is cinacalcet. Cinacalcet is slightly soluble in water and very soluble in some organic solvents such as methanol and ethanol. Cinacalcet has solubility in water of less than about 1 ug/mL at neutral pH. The solubility of cinacalcet can be increased to 1.6 mg/mL when the pH ranges from about 3 to about 5. However, when the pH is about 1, the solubility decreases to 0.1 mg/mL. Such limited solubility results in low bioavailability of cinacalcet. Further, it also reduces the number of formulations and drug delivery options for cinacalcet,
Cinacalcet is a moiety which is highly lipophilic and is chemically known as [(1R)-1-(naphthalen-1-yl) ethyl] ({3-[3-(trifluoromethyl) phenyl] propyl}) amine represented by the following chemical structure:-


Cinacalcet is commercially available under the trade name Sensipar in the United States of America and as Mimpara® in Europe. Cinacalcet is currently available in the dosage form of 30 mg, 60 mg and 90 mg oral tablets.
Cinacalcet belongs to the class of naphthalenes and phenylpropylamines and is a calcimimetic agent indicated in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis, hypercalcemia in patients with parathyroid carcinoma and severe hypercalcemia in patients with primary hyperparathyroidism, who are unable to undergo parathyroidectomy.
Hyperparathyroidism is characterized by high levels of circulating calcium due to an increased secretion of parathyroid hormone by one or more parathyroid glands. Hyperparathyroidism can lead to osteoporosis. Patients with renal failure suffering from secondary hyperparathyroidism have an increased risk of renal bone disease, soft-tissue calcifications and vascular disease.
Patients with chronic kidney disease often have secondary hyperthyroidism (secondary hyperparathyroidism). Kidneys are unable to excrete less phosphate from the urine and the less active form of vitamin D3) which is essential for the maintenance of physiological calcium ion level in the blood. Subsequently, when the calcium ion levels decrease in the parathyroid glands, parathyroid hormone level is elevated. This parathyroid hormone overproduction in turn causes calcium ion mobilization from the bones and the bones become more brittle.
The recommended daily dose of cinacalcet in patients with secondary hyperparathyroidism and end-stage renal disease on dialysis starts at 30 mg, once daily. This dose should be titrated every 2 to 4 weeks up to 180 mg daily, to achieve a target PTH level. For patients with parathyroid carcinoma, the recommended starting oral dose is 30 mg twice daily. This dose should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily and 90 mg three or four times daily as necessary to normalize serum calcium levels.

Cinacalcet reduces the calcium levels by increasing the sensitivity of calcium receptors to extracellular calcium. Cinacalcet binds to the calcium-sensitive receptors on the surface of parathyroid cells. The sensitivity of the receptor is increased in comparison to extracellular calcium ions and simulates a higher serum calcium level than that which actually exists. As a result, PTH secretion decreases, retaining the calcium that is released from the bone.
The major approaches that are undertaken or have been undertaken to address the poor water solubility and the subsequent poor bioavailability of lipophilic drugs, such as cinacalcet, include the pharmaceutics approach (which involves modification of formulation, manufacturing processes or physiochemical properties of the drug), pharmacokinetic approach (which involves altering of pharmacokinetics of drug by modifying its chemical structure) and biological approach (which involves alteration in the route of drug administration).
However, the rate of drug dissolution and drug solubility are very important factors which need to be considered while adopting the biologic approach. The pharmacokinetic approach of chemical modification has an infinite number of drawbacks such as being very expensive, time consuming, requires repetition of chemical studies and risk of precipitating adverse effects. Hence, generally the pharmaceutics approach is mostly preferred as compared to the biologic approach as well as the pharmacokinetic approach.
The pharmacokinetic approach overcomes the problems or issues associated with oral absorption and bioavailability by utilizing various technologies. One such technology is to design a prodrug with the required physico-chemical properties so as to improve its bioavailability.
Although, prodrug approach is the best way of improving the bioavailability, it is a complex technique in itself which requires extensive studies to establish the safety profile of prodrugs in humans which ultimately may result in failure. Furthermore, the potential drawback of this approach is the reduced solubility of the prodrug.

Further, if the drug is not soluble in the desired formulation vehicle, it becomes necessary to solubilize the drug to proceed with the product development. The solubilization techniques include pH adjustment, mixed aqueous/organic cosolvents, organic solvent mixtures, cyclodextrin complexation, liposomes, polymeric gels, use of surfactants and combinations of such techniques. However, the limitations of these approaches include the possibility of precipitation of the drug, pain, inflammation, hemolysis, phlebitis, as well as deleterious effects on drug stability.
Various other strategies or techniques that are undertaken to address the bioavailability issues include complexation, microencapsulation, lipids, permeation enhancers, salt formation, solid dispersions, self emulsifying drug delivery systems etc; however, all such techniques involve use of complex methods or systems and moreover are expensive.
WO2011047837 discloses an intermediate formed by melt granulation or melt extrusion of cinacalcet or its salts with a matrix former or any other excipient.
WO2005034928 discloses an immediate release pharmaceutical composition comprising cinacalcet having a controlled dissolution profile. The application discloses tablets that contain cinacalcet in a micronized range wherein the active ingredient content is about 18% w/w. These tablets are required to be administered with a meal or shortly after a meal, because the bioavailability of cinacalcet is increased by 50 % to 80 % with concomitant food intake. However, micronization of active ingredient may result in low fluidity which may be undesirable. Further during compression, such micronized active ingredients, may ultimately lead to non-uniform drug distribution within the formulation. WO2007124465 discloses anti-irritant emulsion formulations of cinacalcet that are suitable for intravenous injection.
WO2008027522 discloses solid composites of cinacalcet in an immediate and controlled release formulation.
WO2008000422 discloses dispersion of stable amorphous cinacalcet hydrochloride in a matrix material.

WO2008064202 discloses modified release formulations containing cinacalcet and their method of preparation.
WO2010034497 discloses cinacalcet formulations in the form of tablets with bimodal pore size and pH adjusters so as to increase its solubility and stability.
WO2011146583 discloses cinacalcet formulations wherein cincalcet is nanosized below 200 nm to increase its solubility.
WO2012071535 discloses a hard shell capsule containing a granular powder formulation of cinacalcet which can be sprinkled on and mixed with food or drinks and then administered orally to pediatric patients.
Thus, employment of various complex techniques may enable us to solve the bioavailability problems that are associated with poor water soluble drugs, like cinacalcet, but however, may not produce or result in a cost effective dosage form.
Although the prior arts disclose different types of compositions which address the solubility issues of cinacalcet, most of these solubility enhancing techniques involve critical and tedious steps during manufacture or may have to be modified according to the specific physicochemical characteristics of cinacalcet.
Further, although a number of alternative technologies are being developed for enhancing the bioavailability; lipid-based formulations have always seemed promising for lipophilic drugs. Such lipid-based formulations commonly make use of excipients which are either liquid or semi-solid in nature.
Accordingly, the inventors of the present invention have adopted an approach to develop a dosage form of cinacalcet, which is cost effective, can be produced by simple manufacturing techniques and can maximize the solubility of cinacalcet from such dosage form as well as improve its bioavailability. These objectives have been achieved by developing a liquid and semi-solid compositions of cinacalcet and such compositions are encapsulated in soft or hard gelatin capsules.

OBJECT OF THE INVENTION;
An object of the present invention is to provide a pharmaceutical composition comprising cinacalcet having improved solubility.
Another object of the present invention is to provide a pharmaceutical composition comprising cinacalcet having improved bioavailability.
Yet another object of the present invention is to provide a pharmaceutical composition comprising cinacalcet which can preferably be administered without food.
Another object of the present invention is to provide a pharmaceutical composition comprising cinacalcet wherein the total daily dose of cinacalcet is less than the conventionally administered daily dose.
Another object of the present invention is to provide a process for preparing a pharmaceutical composition comprising cinacalet.
Another object of the present invention is to provide a method for treatment for secondary hyperparathyroidism, hypercalcemia in patients with parathyroid carcinoma, severe hypercalcemia in patients with primary hyperparathyroidism administering a pharmaceutical composition comprising cinacalcet.
SUMMARY OF THE INVENTION:
According to an aspect, there is provided a pharmaceutical composition comprising cinacalcet and optionally one or more pharmaceutical^ acceptable excipients thereof. According to another aspect, there is provided a process of manufacturing pharmaceutical composition comprising cinacalcet or its pharmaceutically acceptable salts, solvates, hydrates, esters, derivatives, and one or more pharmaceutical ly acceptable excipients thereof.
According to yet another aspect, there is provided a method of treating secondary hyperparathyroidism, hypercalcemia in patients with parathyroid carcinoma, severe

hypercalcemia in patients with primary hyperparathyroidism administering a pharmaceutical composition comprising cinacalcet.
According to another aspect, there is provided a use of the pharmaceutical composition comprising cinacalcet in the manufacture of a medicament for treating secondary hyperparathyroidism, hypercalcemia in patients with parathyroid carcinoma, severe hypercalcemia in patients with primary hyperparathyroidism.
DETAILED DESCRIPTION OF THE INVENTION:
Cinacalcet is slightly soluble in water, therefore, formulating a suitable composition of cinacalcet which is easy to manufacture as well as which alleviates the solubility and bioavailability problems is a challenge.
Thus the inventors have found that the solubility properties and bioavailability of cinacalcet can be improved by developing a liquid and/or semi-solid compositions of cinacalcet.
Thus, the inventors of the present invention have developed a dosage form comprising a liquid and/or semi-solid pharmaceutical compositions of cinacalcet.
The term "Cinacalcet" is used in broad sense to include not only "Cinacalcet free base" per se but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable esters, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes etc.
The term "salt" as used herein, refers to salts derived from inorganic or organic acids.
Examples of suitable salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride,

carbonates, bicarbonates, hydrobromide, hydrolodide, 2-hydroxy-ethanesulfonate, lactate, maleate, mandelate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 2-phenylpropionate, picrate, pivalate, propionate, salicylate, succinate, sulfate, nitrates, tartrate, sulfonates, thiocyanate, tosylate, mesylate, and undecanoate.
When cinacalcet includes an acidic function such as a carboxy group, suitable pharmaceutically acceptable salts for the carboxy group that are well known to those skilled in the art would also include, for example, alkaline, alkaline earth, ammonium, quaternary ammonium cations and the like in the ambit of the invention.
The term "pharmaceutically acceptable" mentioned throughout the specification would be applied to a carrier, diluent or excipient which is compatible with the actives as employed.
The term "administration without food" mentioned throughout the specification means that the patient can take the pharmaceutical composition of the present invention with meals, but need not necessarily have to take the pharmaceutical composition of the present invention with meals.
The term "therapeutically effective amount" as used herein, is an amount that alters the calcium level, the phosphorus level, the PTH level, and the calcium phosphorus product in a subject in a desired manner.
The term "liquid and/or semi-solid' mentioned throughout the specification would refer to cinacalcet and optionally, one or more pharmaceutically acceptable excipients, in the form of solution and/or partially in the form of finely divided particles suspended freely in a suitable vehicle and encapsulated in a soft or hard gelatin capsules.
Soft gelatin capsules are a suitable dosage form for the administration of liquids, suspensions, pastes and the like. Soft gelatin capsules are an effective delivery system, especially for poorly soluble drugs, because the capsules can contain liquid and/or semisolid ingredients that help increase solubility or permeability of the drug across the

membranes in the body. Such liquid and/or semi-solid ingredients are difficult to include in any other solid dosage form such as a tablet. Also the soft gelatin capsules ease the ingestion process and exhibit uniform drug distribution at the site of action where the active ingredient is released, thus improving the bioavailability.
According to one embodiment, the present invention provides a pharmaceutical composition comprising a liquid and/or semi-solid, a shell comprising gelatin, carrageenan or HPMC surrounding the said liquid fill.
In other words, cinacalcet may be partially in the form of solution and/or partially in the form of finely divided particles suspended freely in the liquid and/or semi-solid which makes cinacalcet readily absorbed the moment the intestinal soluble gelatin, carrageenan or HPMC shell is dissolved.
The pharmaceutical composition, of the present invention, alleviates the solubility and bioavailability problems of cinacalcet and is advantageous over the existing dosage forms
of cinacalcet.
The present invention thus further provides a pharmaceutical composition comprising cinacalcet in the form of capsules made of gelatin, carrageenan or HPMC optionally with one or more pharmaceutical ly acceptable excipients.
Suitable solvents/co-solvents or vehicles, that may be employed, in the pharmaceutical composition comprising capsules of cinacalcet include, but are not limited to, medium and/or long chain fatty acids or glycerides, monoglycerides, diglycerides, triglycerides, structured triglycerides, soyabean oil, peanut oil, corn oil, corn oil mono glycerides, corn oil di glycerides, corn oil triglycerides, polyethylene glycol, caprylocaproyl macroglycerides, caproyl 90, propylene glycol, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil derivatives, castor oil, cottonseed oil, olive oil, safflower oil, peppermint oil, coconut oil, palm seed oil, water, beeswax,, oleic acid, methanol, ethanol, isopropyl alcohol, butanol, acetone, methylisobutyl ketone, methylethyl ketone or mixtures thereof.

Suitable solubilizer that may be employed in the pharmaceutical composition comprising capsules of cinacalcet include, but are not limited to, lineleoyl polyoxyl-6-glycerides, corn oil mono glycerides, corn oil di glycerides, corn oil triglycerides or mixtures thereof. Suitable surfactant that may be employed in the pharmaceutical composition comprising capsules of cinacalcet include, but are not limited to, amphoteric, non-ionic, cationic or anionic surfactants, such as, but not limited to, polyoxyethylene castor oil derivatives (for example, polyoxyethyleneglyceroltriricinoleate or polyoxyl ethylene castor oil (or polyoxyethylene glycerol oxystearate, glycerol polyethylene glycol oxystearate, polyethylene glycol hydrogenated castor oil, or block copolymers of ethylene oxide and propylene oxide, also known as polyoxyethylene polyoxypropylene block copolymers or polyoxyethylene polypropylene glycol, or a mono fatty acid ester of polyoxyethylene sorbitan, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate or a sorbitan fatty acid ester (including sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan stearate) or mixtures thereof.
Suitable antioxidants may also be employed in the pharmaceutical composition comprising capsules of cinacalcet, such as, but not limited to, propyl gallate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E, vitamin E acetate, vitamin E TGPS and ascorbic acid or mixtures thereof.
In one aspect of the present invention, the pharmaceutical composition may comprise capsules of cinacalcet enabling the capsules to be resistant to gastric juices and to be soluble in the intestine which have an enteric polymer coating.
Enteric coat polymers that may be used in the pharmaceutical composition comprising capsules of cinacalcet include, but are not limited to, free acid forms of hydroxypropyl methyl cellulose phthalate, alkylmethacrylate and' methacrylic acid ester copolymers, polyvinylacetate phthalate and the like or their ammonia or alkali metal salts or mixtures thereof.
According to one embodiment, of the present invention, the pharmaceutical composition comprising capsules of cinacalcet may be administered without food.

According to another embodiment of the present invention, the pharmaceutical composition comprising capsules of cinacalcet may comprise a therapeutically effective amount of cinacalcet which is less than the conventionally administered daily dose.
In another aspect of the present invention, the pharmaceutical composition of the present invention may also be formulated in a suitable oral liquid dosage form, including, but not limited to emulsions, solutions, suspensions, syrups, and elixirs.
Pharmaceutical^ acceptable excipients, that may be employed the oral liquid dosage forrn include, but are not limited to, sweeteners, vehicle/wetting agents, coloring agents, flavoring agents, preservatives, and viscosity enhancing/thickening agents.
Suitable viscosity enhancing/thickening agents, which may be used in the pharmaceutical composition of the present invention, include, but are not limited to methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxy ethyl propyl cellulose, starches (such as maize or corn Starch, potato starch, rice starch, tapioca starch, and wheat starch), carboxyvinyl polymers (carbomers such as Carbopol®), carboxymethyl cellulose and salts thereof, microcrystalline cellulose and arabic gum, guar gum, and xanthan gum and mixtures thereof.
Suitable vehicle/wetting agents which may be used in the pharmaceutical composition of the present invention include, but are not limited to glycerol, propylene glycol, liquid polyethylene glycols, sorbitol and mixtures thereof.
suitable flavouring agents which may be used in pharmaceutical composition, of the present invention include, but are not limited to cherry, raspberry, pineapple, black currant, strawberry, caramel chocolate, mint cool, fantasy, meat flavours and the like or mixtures thereof.
Suitable sweeteners which may be used in the pharmaceutical composition of the present invention include, but are not limited to, saccharin, aspartame acesulfame, cyclamate, alitame, dihydrochalcone sweetener, monellin, neohesperidin, neotame, stevioside and sucralose, their pharmaceutically acceptable salts and mixtures thereof.

Suitable colouring agents which may be used in the pharmaceutical composition of the present invention include, but are not limited to quinoline yellow or mixtures thereof.
Suitable preservatives which may be used in the pharmaceutical composition of the present invention include, but are not limited to, sodium benzoate, benzoic acid, potassium sorbate, sorbic acid, methyl p-hydroxibenzoate, ethyl p-hydroxibenzoate, propyl p-hydroxibenzoate, butyl p-hydroxibenzoate, sodium methyl p-hydroxibenzoate, sodium ethyl p-hydroxibenzoate, sodium propyl p-hydroxibenzoate, sodium butyl p-hydroxibenzoate, domiphen bromide, sodium propionate, propylene glycol and mixtures thereof.
According to one embodiment, the pharmaceutical composition, according to the present invention, may comprise therapeutically effective amount of cinacalcet which is present in an amount from about 1 mg to about 360 mg, from about 5 mg to about 240 mg, from about 20 mg to about 100 mg.
Poorly water-soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Improvement in the extent and rate of dissolution is highly desirable as this can lead to more reproducible oral bioavailability, subsequently leading to dose reduction and more reliable therapy.
Physical modifications of the drug particles such as micronization aim to increase the surface area, solubility and/or wettability of the powder particles. Micronization is used to elevate drug activity by increasing particle surface or by allowing active substances to reach their site of action by reducing particle size.
The active in micronized form can be obtained by any of the processes such as, but not limited to, ball milling, jet milling, sonication, homogenization and solvent precipitation. The pharmaceutical composition of the present invention may also comprise the active in a nanosized form.
Nanonization of hydrophobic or poorly water-soluble drugs generally involves the ' production of drug nanocrystals through either chemical precipitation (bottom-up

technology) or disintegration (top-down technology). Different methods may be utilized to reduce the particle size of the hydrophobic or poorly water soluble drugs. [Huabing Chen et ah, discusses the various methods to develop nanoformulations in "Nanonization strategies for poorly water-soluble drugs," Drug Discovery Today, Volume 00, Number 00, March 2010].
Nanosizing leads to increase in the exposure of surface area of particles leading to an increase in the rate of dissolution.
The nanoparticles of the present invention can be obtained by any of the processes such as, but not limited to, milling, precipitation, homogenization, high pressure homogenization, spray drying, spray-freeze drying, supercritical fluid technology, double emulsion/solvent evaporation, PRINT (Particle replication in non-wetting templates), thermal condensation and ultrasonication.
The pharmaceutical composition of the present invention can be manufactured by any of the processes as described above.
Further, the pharmaceutical composition according to the present invention may also comprise at least one or more active ingredient such as, but not limited to, calcium receptor-active compounds, vitamins and their analogs such as vitamin D, antibiotics and cardiovascular agents.
The present invention also provides a process(s) to manufacture the pharmaceutical composition according to the present invention.
The present invention provides a process of preparing a capsule; said process comprises dispersing or dissolving cincalcet in a solvent/co-solvent or a suitable vehicle to obtain a liquid fill and filling it in capsules of gelatin, carragenan or HPMC.
The present invention provides a process of preparing a liquid and/or semi solid dosage forms of cinacalcet, said process comprises dispersing or dissolving cinacalcet along with

pharmaceutically acceptable excipients or encapsulation of such liquid and/or solid compositions in soft or hard gelatin capsules,
Accordingly, the pharmaceutical composition, in the form of soft or hard gelatin capsules are subjected to suitable filling and sealing techniques.
The present invention also provides a method of treating secondary hyperparathyroidism, hypercalcemia m patients with parathyroid carcinoma, severe hypercalcemia in patients with primary hyperparathyroidism which method comprises administration of a therapeutically effective amount of a pharmaceutical composition according to the present invention.
The present invention also provides a use of the pharmaceutical composition in the manufacture of a medicament for the treatment of secondary hyperparathyroidism, hypercalcemia m patients with parathyroid carcinoma, severe hypercalcemia in patients with primary hyperparathyroidism.
The following examples are for the purpose of illustration of the invention only and are not intended in any way to limit the scope of the present invention.
Example 1

Sr. No. Ingredient Weight (mg)
1 Cinacalcet HCI/ methanesulfonate 99.19
2 Mono and Di glycerides q.s. 200-2000
3 Butylated hydroxy toulene 0.02-1
4 Ethanol 30-300
Process
1) Cincalcet was dissolved or dispersed in monoglycerides or diglycerides and
ethanol
2) The solution dispersion so obtained in step (I) was filled in capsules of gelatin,
carrageenan or HPMC.

Example 2

Sr. No. Ingredient Weight (mg)
1 Cinacalcet HC1/ methanesulfonate 99.19
2 Butylated hydroxy toulene 0.02-1
3 Ethanol 30-300
4 Propylene Glycol q.s. 200-2000
Process
1) Cincalcet was dissolved or dispersed in ethanol and propylene glycol
2) The solution or dispersion so obtained in step (1) was filled in capsules of gelatin, carrageenan or HPMC.
Example 3

Sr. No. Ingredient Weight (mg)
1 Cinacalcet HC1/ methanesulfonate 99.19
2 Mono and Di glycerides 200-2000
3 Butylated hydroxy toulene 0.02-1
4 Transcutol P q.s. 30-200
Process
1) Cincalcet was dissolved or dispersed in monOglycerides or diglycerides and transcutol
2) The solution or dispersion so obtained in step (1) was filled in capsules of gelatin, carrageenan or HPMC.
Example 4

Sr. No. Ingredient Weight (mg)
1 Cinacalcet HCI/ methanesulfonate 99.19
2 Butylated hydroxy toulene 0.02-1
3 Transcutol 100-300
5 Glyceryl monolinoleate 50-200

5 Polyoxyl 40 hydrogenated castor oil 50-600
6 Propylene Glycol q.s. 500-1500
Process
1) Cincalcet was dissolved or dispersed in transcutol, glyceryl monolinoleate and polyoxyl 40 hydrogenated castor oil
2) The solution or dispersion so obtained in step (1) was filled in capsules of gelatin, carrageenan or HPMC.
Example 5

Sr. No. Ingredient Weight (mg)
1 Cinacalcet HCI/ methanesulfonate 99.19
2 Butylated hydroxy toulene 0.02-1
3 Ethanol 30-300
4 Glyceryl monolinoleate 50-200
5 Polyoxyl 40 hydrogenated castor oil 50-600
7 Propylene Glycol q.s. 500-1500
1) Cincalcet was dissolved or dispersed in ethanol, glyceryl monolinoleate, polyoxyl 40 hydrogenated castor oil and propylene glycol.
2) The solution or dispersion so obtained in step (1) was filled in capsules of gelatin, carrageenan or HPMC.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.

It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example reference to a "cosolvent" refers to a single cosolvent or to combinations of two or more cosolvents, and the like.

WE CLAIM:
1) A pharmaceutical composition comprising cinacalcet or its pharmaceutically acceptable salts, solvates, esters, hydrates, enantiomers, derivatives, polymorphs, prodrugs, complexes.
2) A pharmaceutical composition according to claim 1, provided as an oral liquid dosage in the form of an emulsion, solution, suspension, syrup or elixir.
3) A pharmaceutical composition according to claim 1, provided as a liquid and/or semi solid in a capsule.
4) A pharmaceutical composition according to any preceding claims further comprising one or more pharmaceutically acceptable excipients comprising one or more vehicle, solubilizer, surfactant, antioxidant sweeteners, wetting agents, coloring agents, flavoring agents, preservatives, and thickening agents.
5) A pharmaceutical composition according to any preceding claims, wherein cinacalcet is in a nanosize form.
6) A pharmaceutical composition according to any preceding claims, wherein cinacalcet is present in an amount from about 5 mg to about 240 mg.
7) A pharmaceutical composition according to any preceding claims, wherein cinacalcet may be administered without food.
8) A pharmaceutical composition according to any preceding claims, further comprising at least one or more of a calcium receptor-active compounds, vitamins and their analogs such as vitamin D, antibiotics and cardiovascular agents.
9) A process for preparing a pharmaceutical composition comprising cinacalcet, which process comprises dispersing or dissolving cincalcet along with

pharmaceutically acceptable excipients to form an oral liquid dosage form or a liquid and/or semi solid and filling it in capsules of gelatin, carragenan or HPMC.
10) A pharmaceutical composition substantially as herein described with reference to the examples.