Field of the Invention

This invention in general relates to an improved drug delivery system of Citalopram hydrobromide and process for producing the same. More particularly the invention provides for devising pellets formulation of Citalopram hydrobromide and disposing the same into a capsule and a process for producing the same.

Background of the Invention

Citalopram hydrobromide belongs to a general class of antianxiety and antidepressant drugs. It is highly selective and potent serotonin reuptake inhibitor with minimal effects on the neuronal reuptake of norepinephrine and dopamine. The ability of citalopram to potentiate serotonergic activity in the central nervous system via inhibition of the neuronal reuptake of serotonin is thought to be responsible for its antidepressant action.

The prior art discloses many systems for the delivery of citalopram hydrobromide such as film-coated tablets, hard gelatin capsules, sustained release tablets etc.

International Application WOOl /80619 A2 discloses a solid unit dosage form comprising citalopram, which is prepared by direct compression of a mixture of citalopram base or a salt and excipients, or by filling of the mixture in a hard gelatin capsule. Large crystals of a pharmaceutical salt of citalopram and method for the manufacture of large crystals are also disclosed.

International Application WO02/053133 Al discloses a solid unit dosage form containing citalopram prepared by a process in which the citalopram base or its salt and excipients (binder and filler) is mixed by conventional mixing and is compacted on a roller compactor.

In international publication number WO 01/22941A1 discloses melt granulated composition and modified release dosage form prepared from said composition by one

(or) more hydrophilic cellulose other polymers or a hydrophilic melt binder and (or) a therapeutically active ingredient.

International Application WO 00/015219 discloses a pharmaceutical composition comprising a first component (a) which is (R)-3- N,N-dicyclobutylamino-8-fluoro-3,4- dihydro-2-H- 1 -benzopyran-5-carboxamide hydrogen-(2R,3R)-tartrate monohydrate

(NAD 299) and a second component (b) which is citalopram, as the racemate or an enantiomer thereof in the form of its free base, or a pharmaceutically acceptable salt and/or solvate thereof, the preparation thereof, pharmaceutical formulations containing said composition, use of and a method of treatment of affective disorders such as mood disorders and anxiety disorders with said composition as well as a kit containing said composition.

However, tablets or capsules are generally made either by granulation method or direct compression method. In both the methods, the dust generation during the process is very high. Being a potent drug, even in low dosage, exposure for longer period may cause unnecessary side effects for the people who are working in the manufacturing of the medicament.

There was, therefore, a need to develop an improved pharmaceutical delivery device which could avoid the limitations present in the prior art like dust generation during manufacturing, film coating etc.

Summary of the Invention

In accordance with one preferred embodiment of the present invention, there is provided an improved drug delivery system wherein the system comprises pellets of Citalopram hydrobromide disposed into a capsule whereby the system enables better bioavailability due to homogeneous distribution of the drug.

In accordance with another embodiment of the present invention, there is provided a process for producing pellets of citalopram hydrobromide. The process comprises, solubilising Citalopram hydrobromide in a mixture of isopropyl alcohol and water to make a homogeneous solution and stirring the same for 10 to 15 minutes after adding

fillers, binders, glidants, plastcizers and spraying uniformly on neutral pellets. This provides better content uniformity than conventional dosage forms and avoids dust generation.

Another embodiment of the present invention provides a process for producing pellets of citalopram hydrobromide, wherein the process comprises mixing Citalopram hydrobromide with suitable excipients like fillers, binders, glidants, plastcizers, and passing the same through spheronizer to form pellets.

In accordance with yet another embodiment of the present invention, there is provided a process for producing sustained release pellets of citalopram hydrobromide, wherein the process comprises mixing Citalopram hydrobromide with suitable excipients and passing the same through spheronizer to make pellets and coating the pellets with suitable polymer, selected from a group comprising, hydroxy propyl methyl cellulose, cellulose derivatives, methacrylic acid copolymer, ethyl cellulose, sodium alginate, guar gum, xanthan gum, carbopol, alginate derivative or a mixture thereof, to get desired drug release profile.

in accordance with yet another embodiment of the present invention, there is provided an improved drug delivery system wherein the pellets formed by the above process are disposed in a capsule.

Detailed Description of the Invention

The present invention aims at providing an improved drug delivery system and process for producing the same. According to the preferred embodiment the system is a capsule, which contains pellets form of citalopram hydrobromide.

The capsule disclosed in the invention can be any kind of capsule like hard gelatin or soft gelatin capsule.

The pellets used for filling in the capsules are immediate release pellets or sustained release pellets.

The pellets, which are to be sprayed with the active substance, can be neutral pellets. The quantity of the pellets is not essential for the present invention and may vary between approximately 20 to 88%. The pellets coated with active substance are produced by dissolving the active in a solubiliser and mixing with other pharmaceutically acceptable excipients, which include fillers, binders, glidants, plastcizers etc. and spraying on non-pareil seeds. Pellet layering is done by spray coating/layering equipment.

Before the pellets are sprayed, the active substance may be mixed with further components. Such components can be filler, binder, glidants, plastcizers, alone or in mixtures.

The solubiliser used in the present invention is selected from a group comprising, Isopropyl alcohol, ethanol, methylene chloride, purified water, acetone or mixture thereof. The percentage range of solubiliser is varied from 10 to 90%.

In the present invention the surface area of the drug is increased to a large extent in comparison to other oral dosage forms because fine particles of drug are coated on pellets due to which solubility of the drug increases.

The diluents / filler used in the invention, can be selected from the group comprising, cellulose derivatives, lactose, maize starch, modified starch, pregelatinised starch, partially hydrolysed starch, calcium salts, magnesium salts, maltodextrin, sorbitol, mannitol, sucrose, mannose etc. Concentration of the diluents / fillers can vary from 1.0 to 75%.

Plasticizers used in the invention are selected from the group comprising, triacetin, polyetheylene glycol, propylene glycol, diethyl phthalate, castor oil alone or mixture thereof. The concentration of the plasticizers can vary from 0.1 to 38%.

The binder used in the invention is selected from starch derivatives, Povidone, gelatin. The concentration of the binder can range from 0.5 % to 20%.

Another process to prepare a pellet of citalopram hydrobromide comprises, mixing

citalopram hydrobromide with suitable pharmaceutical excipients disclosed above and passing through a spheronizer to form immediate release pellets which can be encapsulated in a capsule to provide improved drug delivery system.

To prepare sustained release formulations of citalopram hydrobromide, pellets form containing citalopram hydrobromide are coated with suitable polymers to achieve desired release profile. The polymer used is selected from a group comprising hydroxy propyl methyl cellulose, cellulose derivatives, Methacrylic acid copolymer, ethyl cellulose, sodium alginate, guar gum, xanthan gum, carbopol, alginate derivative, alone or in combination thereof. The concentration of the polymers can vary from 2.0 to 65.0%.

The most preferred polymer is ethyl cellulose. The viscosity of the ethyl cellulose can vary from 5 cps to 100 cps.

Examplel

Citalopram Hydrobromide capsules

Example2

Citalopram Hydrobromide capsules SR

While this invention has been described in detail with reference to certain preferred embodiments, it should be appreciated that the present invention is not limited to those precise embodiments. Rather, in view of the present disclosure, which describes the current best mode for practicing the invention, many modifications and variations would present themselves to those skilled in the art without departing from the scope and spirit of this invention.