DESC:FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:

“PHARMACEUTICAL DEPOT COMPOSITIONS”

2. APPLICANT:

(a) NAME: CIPLA LIMITED

(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 long acting dosage forms comprising ulipristal, a process for preparing such dosage forms and use of the said dosage forms for the treatment of uterine fibroids.

BACKGROUND AND PRIOR ART
Ulipristal is chemically known as 17a-acetoxy-11-[4-N,N-dimethylamino-phenyl)-19-norpregna-4,9-diene-3,20-dione. It has a structural formula as follows:-

Ulipristal acetate possesses antiprogestational and antiglucocorticoidal activity and has been used for contraception, in particular for emergency contraception and for the therapy of various hormonal diseases such as uterine fibroids.

Ulipristal acetate is commercially available as an oral 5 mg tablet under the trade name Esmya® and is indicated for pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. It is also available as an oral 30 mg tablet under the trade name ellaOne® and is indicated for emergency contraception within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure.

Uterine fibroids also called as leiomyomata are common pelvic fibroid tumors occurring in up to 20% of women over 30 years of age. Leiomyomata represent one of the most frequent indications of surgical procedures in woman of reproductive age. Studies show that up to 77% of women have microscopic or macroscopic uterine fibroids at the time of menopause (Cramer et al, 1990). Leiomyomata may be 1 mm to 20 cm in diameter.

Leiomyomata are monoclonal sex-hormone responsive tumors of myometrial cells with abundant extra cellular collagen matrix. The histological appearance is similar to that of normal myometrium surrounded by a pseudocapsule of compressed myometrium, although areas of fibrosis and calcification (thought to represent degeneration) may be present.

Leiomyomata are almost always benign in pre-menopausal women but may be indistinguishable from leiomyosarcomas, a tumor most common in post-menopausal women. Leiomyomata management includes administration of gonadotropin-releasing hormone agonists, progesterone modulators and surgery. Other options such as uterine fibroid embolization, magnetic resonance imaging-guided focused ultrasound, and radiofrequency ablation are used to avoid more invasive surgery. If surgery is desired or required, often less invasive approaches via hysteroscopy for intracavitary lesions or robot-assisted laparoscopy for patients with a small number of myomas have become preferred options.

WO2010066749 discloses a pharmaceutical tablet for oral administration comprising ulipristal acetate in an amount of 3 to 18 weight %, together with excipients.

WO2009095418 discloses a method for treating uterine fibroids or tumors by administering ulipristal acetate.

Ulipristal acetate is indicated for pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The duration of treatment is limited to 3 months. The treatment consists of one tablet of 5 mg to be taken orally once daily for up to 3 months. Treatment should be started during the first week of a menstrual cycle.

Further, if a patient misses a dose, the patient should take ulipristal acetate as soon as possible. If the dose was missed by more than 12 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.

Hence, a drug delivery technology, especially depot preparations which can reduce the total number of such administration would be preferred. Such reductions in frequency of drug dosing in practice may be achieved through the use of injectable depot formulations that are capable of releasing drugs in a slow but predictable manner and consequently improve patient compliance.

Such depot preparations exhibit constant plasma concentration-time profiles and have the potential to not only boost the therapeutic benefit in most cases, but may also reduce any unwanted events, such as immunogenicity.

OBJECT OF THE INVENTION:
An object of the present invention is to provide a pharmaceutical depot composition comprising ulipristal.

Another object of the present invention is to provide a pharmaceutical depot composition comprising ulipristal optionally with one or more pharmaceutically acceptable excipients.
Yet another object of the present invention is to provide a pharmaceutical depot composition comprising ulipristal to ensure patient compliance.

Another object of the present invention is to provide a process for preparing a pharmaceutical depot composition comprising ulipristal optionally with one or more pharmaceutically acceptable excipients.

Another object of the present invention is to provide a method of treating or reducing uterine fibroids by administering a pharmaceutical depot composition comprising ulipristal.

Another object of the present invention is to provide the use of treating or reducing uterine fibroids by administering a pharmaceutical depot composition comprising ulipristal.

SUMMARY OF THE INVENTION:
According to an aspect of the present invention, there is provided a pharmaceutical depot composition comprising ulipristal or any of their pharmaceutically acceptable salts, solvates, hydrates, esters, enantiomers, polymorphs, prodrugs, complexes, derivatives thereof.

According to another aspect of the present invention, there is provided a pharmaceutical depot composition comprising ulipristal along with at least one or more pharmaceutically acceptable excipients.

According to yet another aspect of the invention, there is provided a process for the preparation of a pharmaceutical depot composition comprising ulipristal along with one or more pharmaceutically acceptable excipients.

According to yet another aspect of the present invention there is provided a method of treating or reducing uterine fibroids by administering pharmaceutical depot composition comprising ulipristal.

According to yet another aspect of the invention there is provided a use of pharmaceutical depot composition comprising ulipristal for treating or reducing uterine fibroids.

DETAILED DESCRIPTION OF THE INVENTION:
Treatment of uterine fibroids with ulipristal acetate in adult women involves administration of one tablet of 5 mg to be taken orally once daily for up to 3 months.
For most drugs such as ulipristal, depending on the dose, it may be possible to reduce such administration frequency from daily to once or twice monthly or even longer (6 months).

Accordingly, pharmaceutical depot composition comprising ulipristal may improve patient comfort and in addition prevent fluctuations of the plasma concentration-time profile. Such constant plasma concentration-time profiles have the potential to not only boost the therapeutic benefit in most cases, but also to reduce any unwanted events, such as immunogenicity etc.
The present invention thus provides a parenteral pharmaceutical depot compositions comprising ulipristal.

The term “Ulipristal” is used in broad sense to include not only “Ulipristal” per se but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable esters, pharmaceutically acceptable derivatives, pharmaceutically acceptable hydrate, pharmaceutically acceptable polymorphs, pharmaceutically acceptable isomer, pharmaceutically acceptable tautomer, pharmaceutically acceptable anhydrate, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes etc.

In some embodiments, the pharmaceutical depot compositions may comprise any other pharmaceutically acceptable salt of ulipristal including, but not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, hydrochloride, hydrobromide, hydroiodide, acetate, nitrate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, tocopheryl succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, ß-hydroxybutyrate, glycollate, tartrate, methanesulfonate, propanesulfonate, naphthalene-2-sulfonate, p-toluenesulfonate, mandelate and the like salts.

The term “parenteral” as used herein refers to routes selected from subcutaneous (SC), intravenous (IV), intramuscular (IM), intradermal (ID), intraperitoneal (IP) and the like.
The term "pharmaceutical depot composition" includes injection preparations, such as liquid dosage forms (liquids, liquid dispersions, suspensions, solutions, emulsions), gels, implants (rods, capsules, rings) biodegradable or non-biodegradable microparticles/microspheres in the form of controlled release formulations, lyophilized formulations, delayed release formulations, extended release formulations, pulsatile release formulations, and mixed immediate release and controlled release formulations etc. may also be envisaged under the ambit of the invention.

Microspheres, implants and gels are the most common forms of biodegradable polymeric devices used in prolonging the release of drugs in the body. Besides biodegradable systems, there are non-biodegradable implants and infusion pumps that can be worn outside the body.

In certain embodiments, the dosage forms include, but are not limited to, biodegradable injectable depot systems such as, PLGA based injectable depot systems; non-PLGA based injectable depot systems, and injectable biodegradable gels or dispersions.

The term “biodegradable” as used herein refers to a component which erodes or degrades at its surfaces over time due, at least in part, to contact with substances found in the surrounding tissue fluids, or by cellular action.

The term “long acting” as used herein refers to a pharmaceutical depot composition which provides prolonged, sustained or extended release of the ulipristal salt to the general systemic circulation of a subject or to local sites of action in a subject. This term may further refer to a pharmaceutical depot composition which provides prolonged, sustained, controlled or extended duration of action (pharmacokinetics) of the ulipristal salt in a subject.

The term 'low dose' as used herein refers to a therapeutically effective dose of ulipristal, which dose is less than the usual or the conventional dose required to produce the therapeutic effect.

In particular, the long acting pharmaceutical depot compositions of the present invention provide a dosing regimen which ranges from once weekly to once every 6 months.

Depending on the duration of action required, each depot or implantable device of the present invention will typically contain ulipristal, designed to be released over a period ranging from a couple of weeks to a number of months.
Preferably, the long acting pharmaceutical depot compositions of the present invention are administered in a dose which is less than the conventionally administered dose.

In one embodiment, the present invention provides a long acting pharmaceutical depot composition comprising a therapeutically effective amount of ulipristal acetate or any other pharmaceutically acceptable salt of ulipristal in a depot form suitable for administration at a medically acceptable location in a subject in need thereof.

The present invention thus provides long acting parenteral pharmaceutical depot compositions comprising a therapeutically effective amount of a pharmaceutically acceptable salt of ulipristal, e.g., ulipristal acetate.

In particular, the present invention provides a long acting pharmaceutical depot compositions comprising a therapeutically effective amount of ulipristal salt in a depot form, suitable for parenteral administration at a medically acceptable location in a subject in need thereof.

Further, the long acting pharmaceutical depot compositions provide equal or superior therapeutic efficacy to the commercially available dosage form, with reduced incidence and/or severity of side effects at the local and/or systemic levels.

According to one embodiment, the pharmaceutical depot composition is in the form of microspheres, implants, solutions, suspensions, microemulsions, and the like, that are suitable for subcutaneous or intramuscular administration of ulipristal salts such as ulipristal acetate.

According to another embodiment, the pharmaceutical depot composition comprises a pharmaceutically acceptable biodegradable or non-biodegradable carrier/s for ulipristal salts such as ulipristal acetate.

In some embodiments, the pharmaceutical depot compositions of the present invention include, but are not limited to, suspensions of ulipristal or a pharmaceutically acceptable salt thereof in water, oil or wax phase; poorly soluble polyelectrolyte complexes of ulipristal or a pharmaceutically acceptable salt thereof; “in-situ” gel-forming matrices based on the combination of water-miscible solvent with ulipristal or a pharmaceutically acceptable salt thereof; and biodegradable polymeric microparticles with incorporated ulipristal or a pharmaceutically acceptable salt thereof.

In particular, the pharmaceutical depot compositions of the present invention are in the form of injectable microparticles wherein the ulipristal or pharmaceutically acceptable salt thereof is entrapped in a biodegradable or non-biodegradable carrier. The microparticulate compositions of the present invention may comprise a water-in oil-in water double emulsion.

Within the scope of the present invention is a microparticulate composition comprising an internal aqueous phase comprising ulipristal or any pharmaceutically acceptable salt thereof, an oil phase or water-immiscible phase comprising a biodegradable or non-biodegradable polymer and an external aqueous phase. The external aqueous phase may further comprise a surfactant, preferably polyvinyl alcohol (PVA), polysorbate, polyethylene oxide-polypropylene oxide block copolymers or cellulose esters. The terms “oil phase” and “water-immiscible phase” may be used interchangeably herein.

In particular, the biodegradable component is a polymer such as, but not limited to, lactic acid-based polymers such as polylactides e.g. poly (D,L-lactide) i.e. PLA; glycolic acid-based polymers such as polyglycolides (PGA) e.g. Lactel® from Durect; poly (D,L-lactide-co-glycolide) i.e. PLGA, (Resomer® RG-504, Resomer® RG-502, Resomer® RG-504H, Resomer® RG-502H, Resomer® RG-504S, Resomer® RG-502S, from Boehringer, Lactel® from Durect); polycaprolactones such as Poly(e-caprolactone) i.e. PCL (Lactel® from Durect); polyanhydrides; poly(sebacic acid) SA; poly(ricenolic acid) RA; poly(fumaric acid), FA; poly(fatty acid dimmer), FAD; poly(terephthalic acid), TA; poly(isophthalic acid), IPA; poly(p-{carboxyphenoxy}methane), CPM; poly(p-{carboxyphenoxy}propane), CPP; poly(p-{carboxyphenoxy}hexane)s CPH; polyamines, polyurethanes, polyesteramides, polyorthoesters {CHDM: cis/trans- cyclohexyl dimethanol, HD:1,6-hexanediol. DETOU: (3,9-diethylidene-2,4,8,10-tetraoxaspiro undecane)}; polydioxanones; polyhydroxybutyrates; polyalkylene oxalates; polyamides; polyesteramides; polyurethanes; polyacetals; polyketals; polycarbonates; polyorthocarbonates; polysiloxanes; polyphosphazenes; succinates; hyaluronic acid; poly(malic acid); poly(amino acids); polyhydroxyvalerates; polyalkylene succinates; polyvinylpyrrolidone; polystyrene; synthetic cellulose esters; polyacrylic acids; polybutyric acid; triblock copolymers (PLGA-PEG-PLGA), triblock copolymers (PEG-PLGA-PEG), poly (N-isopropylacrylamide) (PNIPAAm), poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) tri-block copolymers (PEO-PPO-PEO), poly valeric acid; polyethylene glycol; polyhydroxyalkylcellulose; chitin; chitosan; polyorthoesters and copolymers, terpolymers; lipids such as cholesterol, lecithin; poly(glutamic acid-co-ethyl glutamate), polycaprolactone, polyhydroxybutyrate, polyorthoesters, polyalkaneanhydrides, gelatin, collagen, oxidized cellulose, polyphosphazene and the like, or mixtures thereof.

The pharmaceutical depot compositions of the present invention may further comprise one or more pharmaceutically acceptable excipient(s) selected from, but are not limited to, surfactants, solvents/co-solvents, water immiscible solvents, water, water miscible solvents, oily components, hydrophilic solvents, hydrophobic solvents, emulsifiers, preservatives, antioxidants, anti-foaming agents, stabilizers, buffering agents, pH adjusting agents, osmotic agents, channel forming agents, osmotic adjustment agents, or any other excipient known in the art.

Suitable wetting agents or surfactants include, but are not limited to, amphoteric, non-ionic, cationic or anionic molecules. Suitable surfactants include, but are not limited to, polysorbates, sodium dodecyl sulfate (sodium lauryl sulfate), lauryl dimethyl amine oxide, docusate sodium, cetyl trimethyl ammonium bromide (CTAB), polyethoxylated alcohols, polyoxyethylene sorbitan, octoxynol, N, N–dimethyldodecylamine–N–oxide, hexadecyltrimethylammonium bromide, polyoxyl 10 lauryl ether, brij® surfactants (polyoxyethylene vegetable-based fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols), bile salts (such as sodium deoxycholate and sodium cholate), polyoxyl castor oil, nonylphenol ethoxylate, cyclodextrins, lecithin, methylbenzethonium chloride, carboxylates, sulphonates, petroleum sulphonates, alkylbenzenesulphonates, naphthalenesulphonates, olefin sulphonates, alkyl sulphates, sulphates, sulphated natural oils and fats, sulphated esters, sulphated alkanolamides, alkylphenols (ethoxylated and sulphated), ethoxylated aliphatic alcohol, polyoxyethylene surfactants, carboxylic esters, polyethylene glycol esters, anhydrosorbitol ester and ethoxylated derivatives thereof, glycol esters of fatty acids, carboxylic amides, monoalkanolamine condensates, polyoxyethylene fatty acid amides, quaternary ammonium salts, amines with amide linkages, polyoxyethylene alkyl and alicyclic amines, N,N,N,N tetrakis substituted ethylenediamines, 2- alkyl 1- hydroxyethyl 2-imidazolines, N -coco 3-aminopropionic acid/ sodium salt N-tallow 3 -iminodipropionate disodium salt, N-carboxymethyl n dimethyl n-9 octadecenyl ammonium hydroxide, n-cocoamidethyl n-hydroxyethylglycine sodium salt and the like, polyoxyethylene, sorbitan monolaurate and stearate, cremophor® (polyethoxylated castor oil), solutol® (ethylene oxide/12-hydroxy stearic acid), polysorbate, tyloxapol and the like or mixtures thereof.

Suitable polymers include, but are not limited to, cellulose derivates (such as hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose polymers, hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylene and carboxymethyl hydroxyethylcellulose or any combination thereof); and acrylics (such as acrylic acid, acrylamide, and maleic anhydride polymers, copolymers or their mixtures thereof) and the like or mixtures thereof.

Suitable oils include, but are not limited to, castor oil, medium chain triglycerides (MCTs), mineral oils, vegetable oils, oily fatty acids, oily fatty alcohols, esters of sorbitol, fatty acids, oily sucrose esters, and the like any mixtures thereof. Examples of suitable vegetable oils include cotton seed oil, ground nut oil, corn oil, germ oil, olive oil, palm oil, soybean oil, sweet almond oil, sesame oil, and the like any mixtures thereof. Examples suitable of mineral oils include silicone oil, petrolatum oil, liquid paraffin and the like or any mixtures thereof. Examples of suitable medium chain triglycerides include coconut oil; hydrogenated oils comprising hydrogenated cottonseed oil, hydrogenated palm oil, hydrogenated castor oil, hydrogenated soybean oil and the like or any mixtures thereof.

Suitable solvents/co-solvents/vehicles include, but not limited to, alcohols, dimethyl isosorbide, methylene chloride, water for injection, dimethyl acetamide, triacetin, diacetin, tributyrin, triethyl citrate, tributyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, triethylglycerides, triethyl phosphate, diethyl phthalate, diethyl tartrate, mineral oil, polybutene, silicone fluid, glylcerin, ethylene glycol, polyethylene glycol, octanol, ethyl lactate, propylene glycol, propylene carbonate, ethylene carbonate, butyrolactone, ethylene oxide, propylene oxide, N-methyl-2-pyrrolidone, 2-pyrrolidone, glycerol formal, glycofurol, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethyl formamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and 1-dodecylazacyclo-heptan-2-one, and the like or mixtures thereof.

Suitable anti-foaming agents include, but are not limited to, silicon emulsions or sorbitan sesquioleate and the like or mixtures thereof.

Suitable stabilizers to prevent or reduce the deterioration of the components in the compositions of the present invention include, but are not limited to, antioxidants such as glycine, a-tocopherol or ascorbate, BHA, BHT, and the like or mixtures thereof.

Suitable tonicity modifiers include, but are not limited to, mannitol, sodium chloride, glucose and the like or mixtures thereof.

Suitable buffering agents include, but are not limited to, acetates, phosphates, citrates with suitable cations and the like or mixtures thereof.

Suitable preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride and cetyl pyridinium chloride, benzyl bromide, benzyl alcohol, disodium EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, acetate and phenylmercury borate, polymyxin B sulphate, chlorhexidine, methyl and propyl parabens, phenylethyl alcohol, quaternary ammonium chloride, sodium benzoate, sodium propionate, stabilized oxychloro complex, sorbic acid and the like or their mixtures thereof.

The present invention also provides a process for preparing pharmaceutical depot compositions, which process comprises admixing a pharmaceutically acceptable solvent/s or excipient/s with ulipristal, preferably ulipristal acetate.

The present invention also provides a method of treating or reducing uterine fibroids, comprising the administering pharmaceutical depot composition comprising a therapeutically effective amount of a pharmaceutically acceptable salt of ulipristal, preferably ulipristal acetate.

The present invention also provides a pharmaceutical depot composition for use in treating or reducing uterine fibroids by administering pharmaceutical depot composition comprising a therapeutically effective amount of a pharmaceutically acceptable salt of ulipristal, preferably ulipristal acetate.

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
Intramuscular (IM) Depot Injection - Sterile aqueous suspension
Each ml of sterile aqueous suspension contains-
Sr. No. Ingredients Quantity (mg/ml)
1 Ulipristal acetate 100-150 mg
2 Polyethylene glycol 28.9 mg
3 Polysorbate 80 2.41 mg
4 Sodium chloride 8.68 mg
5 Methylparaben 1.37 mg
6 Propylparaben 0.150 mg
7 Water for injection q. s.
* pH is adjusted with sodium hydroxide or hydrochloric acid, or both.
Process:
1. Propyl paraben and methyl paraben were dissolved in 80% of the quantity of water for injection under stirring.
2. Polyethylene glycol, Polysorbate 80, sodium chloride were added and dissolved in to the solution obtained in step (1) after cooling.
3. Ulipristal was added to the solution obtained in step (2).
4. The suspension obtained in step (3) was sterilized.
5. The suspension obtained in step (4) was homogenized and was filled in the appropriate container.

Example 2
Intramuscular (IM) Depot Injection –
Each ml contains-
Sr. No. Ingredients Quantity (mg/ml)
1 Ulipristal acetate 100-150 mg
2 Sesame Oil 0.5 ml to 1 ml
Process:
1. Ulipristal was dissolved in Sesame oil.
2. The solution obtained in step (1) was filtered and filled in the appropriate container.

Example 3
Intramuscular (IM) Depot Injection - Microspheres
Each ml of sterile aqueous suspension/suspension contains-
Sr. No. Ingredients Quantity (mg/ml)
1 Ulipristal acetate 100-150 mg
2 PLA/PLGA 400-1000 mg
3 Methylene chloride 200-400 mg
4 Carboxymethyl cellulose 1.5-2.0 mg
5 Polyvinyl alcohol 2.5 mg
6 Water for injection q. s.
Process:
1. The drug phase/aqueous phase was prepared by dissolving ulipristal in water for injection.
2. The organic phase was prepared by dissolving the polymer (PLA/PLGA) in methylene chloride.
3. The drug phase obtained in step (1) was added to the organic phase step (2) to form a primary emulsion.
4. Polyvinyl alcohol was added to water for injection to form external aqueous phase.
5. The primary emulsion obtained in step (3) was added to the external aqueous phase obtained in step (4) to form a secondary emulsion.
6. The solvent of the secondary emulsion obtained in step (5) was evaporated to form the microsphere suspension.
7. The suspension obtained in step (6) was concentrated and the residual (poly vinyl alcohol) was washed.
8. The suspension obtained in step (7) was filled in the appropriate container and lyophilized and provided with a sterile diluent for reconstitution (prepared by dissolving Carboxy Methyl cellulose followed by aseptic filtration).

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 fall 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 "an excipient" includes a single excipient as well as two or more different excipients, and the like. ,CLAIMS:We Claim:

1. A pharmaceutical depot composition comprising ulipristal or any of its pharmaceutically acceptable salt, solvate, complex, hydrate, isomer, ester, tautomer, anhydrate, enantiomer, polymorph, prodrug or derivatives thereof and one or more pharmaceutically acceptable excipients.

2. A pharmaceutical depot composition according to claim 1 comprising ulipristal acetate.

3. A pharmaceutical depot composition according to claim 1 or 2, wherein the pharmaceutically acceptable excipients are selected from one or more polymers, surfactants, oils, vehicles, emulsifiers, anti-foaming agents, antioxidants, stabilizers, osmotic agents, channel forming agents, tonicity modifiers, buffering agents and preservatives.

4. A pharmaceutical depot composition according to any preceding claims for parenteral administration.

5. A pharmaceutical depot composition according to claim 4, wherein the dosage form for parenteral administration is in the form of a liquid, gel, implant, biodegradable or non-biodegradable microparticles or microspheres.

6. A pharmaceutical depot composition according to any preceding claims, wherein the dosing regimen ranges from once weekly to once every 6 months.

7. A process for preparing a pharmaceutical depot composition according to any of the preceding claims, wherein the process comprises admixing pharmaceutically acceptable excipients with ulipristal.

8. A pharmaceutical depot composition according to any one of claims 1 to 6 for use in the treatment and reduction of uterine fibroids.
9. A method of treating or reducing uterine fibroids wherein the method comprises administering a pharmaceutical depot composition according to any one of claims 1 to 6.

10. A pharmaceutical depot composition as described herein with reference to the examples.

Dated this 11th day of August, 2014

Dr. P. Aruna Sree
(Regn.No.: IN/PA 998)
Agent for the Applicant
Gopakumar Nair Associates