An orally disintegrating tablet of paroxetine and its process of preparation

Abstract

The present invention relates to an orally disintegrating tablet manufactured by a direct compression method comprising paroxetine or pharmaceutically acceptable salts thereof, at least one disintegrant, at least one diluent, at least one lubricant, and one or more pharmaceutically acceptable excipients. The orally disintegrating tablet prepared using these excipients exhibits desirable properties such as facilitating disintegration, and dissolution of the drug for oral administration. The present invention also relates to the process for preparing the said solid pharmaceutical composition.

Description

Field of the Invention The present invention relates to a pharmaceutical composition of Paroxetine. The present invention relates to an orally disintegrating tablet of Paroxetine or pharmaceutically acceptable salts thereof for oral administration. The present invention also relates to the process of the preparation of the same. Background of the Invention Paroxetine was first disclosed in the U.S. Pat. No. 3912743 Paroxetine hydrochloride belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). A unique feature of this drug is that it is highly potent and selective in its inhibition of serotonin reuptake and has little effect on other neurotransmitters. Paroxetine specifically inhibits the reuptake of serotonin (5-hydroxytryptamine or 5-HT) by blocking the serotonin reuptake transporter (SERT). Serotonin reuptake is a process by which serotonin is taken back into the presynaptic neuron after its release into the synaptic cleft. By inhibiting this reuptake, paroxetine increases the concentration of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. The increased concentration of serotonin in the synaptic cleft results in prolonged and enhanced serotonergic signaling. Serotonin is an important neurotransmitter that regulates mood, emotions, sleep, appetite, and other physiological functions. By enhancing serotonergic signaling, paroxetine helps regulate mood and alleviate symptoms of depression and anxiety. In people with mood disorders like depression and anxiety, there is often an issue with dysregulated or insufficient serotonin levels in certain regions of the brain. Paroxetine helps normalize these levels by preventing the reabsorption of serotonin into the presynaptic neuron, allowing it to remain in the synaptic cleft and exert its effects on postsynaptic receptors. Paroxetine is indicated for the management of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder with and without agoraphobia, which is a fear of open spaces, social anxiety disorders / social phobia (SAD), generalised anxiety disorder, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). The IUPAC name of Paroxetine is (3S,4R)-3-(l,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl) piperidine and the chemical structure is as follow H The paroxetine hydrochloride used can be any pseudopolymorph or polymorph of paroxetine hydrochloride, preferably paroxetine hydrochloride anhydrous or hemihydrate. These two solid-state pseudopolymorph forms are differentiated by their degree of hydration. Form I is a non-hygroscopic hemihydrate and is thermodynamically more stable. Form II is a hygroscopic anhydrate, and does not have water incorporated in its crystalline structure. Paroxetine hydrochloride, which is classified as a BCS class I drug due to its high permeability and high solubility, has an elimination half-life of paroxetine is about 21 hours. Paroxetine is available as a suspension, tablet, extended-release tablet, and capsule. The marketed products of Paroxetine in tablet form are available in four dosage strengths: 10 mg, 20 mg, 30 mg, and 40 mg. while extended-release tablets are available in three dosage strengths: 12.5 mg, 25 mg, and 37.5 mg. The oral suspension is available in two dosage strengths 10mg / 5ml and 20mg / 10ml. The capsule is available in 7.5 mg. There are many prior arts disclosing different formulations of paroxetine as described below: US 2002 / 0032220 Al discloses an oral swallow capsule containing paroxetine dissolved as a solution in a carrier. The process of this invention involves dissolving the paroxetine in a solubilizing agent and blending the resultant solution with an oil or lipid carrier. Further, the prepared paroxetine solution is filled into the capsule. EP 0742715B1 discloses an oral liquid pharmaceutical composition that contains a complex of paroxetine and Amberlite IRP-88. The process of this invention involves combining paroxetine and Amberlite IRP-88 in an aqueous solution. Subsequently, various additional components, including thickening agents like Keltrol and / or Avicel, dispersants such as propylene glycol, a moisture-retaining agent like glycerol, sweeteners like sorbitol and sodium saccharin, buffering agents like citric acid and sodium citrate, preservatives such as sodium benzoate and a mixture of methyl and propyl parabens, artificial colorants like F D and C Yellow No. 6 Sunset Yellow, flavoring agents like Givaudan Natural Orange and / or Lemon, and a silicone anti-foam agent for foam reduction, are also incorporated into the composition. WO2007011139A1 discloses a sustained-release tablet of paroxetine hydrochloride. The process of this invention involves mixing paroxetine hydrochloride and mannitol together to prepare a mixture. Subsequently, a binding solution is prepared by dissolving polyvinyl acetate and either povidone or ethylcellulose in a lower alcohol. The granules are then made by using above prepared mixture and binding solution. At last, the prepared granules are mixed with highly viscous hydroxypropyl methylcellulose, low viscous hydroxypropyl methylcellulose, and a pharmaceutically acceptable excipient, and the tablets are coated for enteric release. US 7,357,945 B2 discloses a tablet of paroxetine which is prepared by wet granulating paroxetine hydrochloride hemihydrate in the presence of povidone, sodium starch glycolate, and dibasic calcium phosphate anhydrous to obtain a granulate, and converting the granulate to a tablet. Finally, the tablet is coated with a suspension of Opadry. US20060216345A1 discloses a formulation of paroxetine hydrochloride hemihydrate in the form of capsules, tablets, pellets, or granules. This composition consists of lactose, pregelatinized starch, sodium starch glycolate, and magnesium stearate. The manufacturing process involves sifting paroxetine hydrochloride hemihydrate, lactose monohydrate, pregelatinized starch, and lactose anhydrous through a 40# mesh. The sifted components are then mixed and formed into granules using water. After drying and milling the granules, the extragranular ingredients, which include lactose anhydrous, sodium starch glycolate, and magnesium stearate, are sifted and combined with the granules. These lubricated granules are subsequently compressed and given a film coating using Opadry Green 13F51312. The solid dosage form of paroxetine presently available has relatively long onset times, which can cause delayed therapeutic effects. Moreover, it also presents a challenge for patients who may have difficulty swallowing tablets and capsules, leading to poor patient compliance. However, the liquid dosage form is bulky, difficult to transport, and takes up a lot of space. Due to their inherent instability, liquid dosage forms often have shorter shelf lives. The patient's measurement of the exact volume determines whether the dose is administered appropriately, which increases the chance for variability. Therefore, alternative dosage forms that are easier to swallow and have a faster onset time need to be explored. An orally disintegrating tablet of the present invention is a pharmaceutical formulation specifically designed in such a way that the entire tablet disintegrates with saliva within a short time when put in the mouth, facilitating easy administration to patients. The orally disintegrating tablet of paroxetine is the best-suited dosage form to formulate, as it offers several benefits, including precise dosing, fast disintegration in the oral cavity without the need for water, fast dissolution, and improved patient adherence, especially for patients who have difficulty swallowing, such as pediatrics and geriatrics suffering from dysphagia. The present invention solves all prior art problems and provides a pharmaceutical composition for oral administration comprising paroxetine. Summary of the Invention In accordance with the present invention, the orally disintegrating tablet for oral administration is prepared. The orally disintegrating tablet comprises Paroxetine or pharmaceutically acceptable salts thereof, at least one disintegrant, at least one diluent, at least one lubricant, and one or more pharmaceutically acceptable excipients. Another embodiment relates to a pharmaceutical orally disintegrating tablet which consists essentially of 0.1 %w / w to about 15 %w / w, preferably in the range from about 0.5 %w / w to about 10 %w / w sodium starch glycolate, wherein the tablet exhibits disintegration within less than 3 minutes, preferably less than 2 minutes. Another embodiment of the present invention is to provide a process for obtaining said orally disintegrating tablet via the direct compression method. Another embodiment of the present invention is to provide taste-masking properties and present pleasant palatability such that the administration of the orally disintegrating tablet is not unpleasant for pediatrics, geriatrics, or unconscious patients, and thus patient compliance is improved. Further another embodiment of the present invention is directed to a method of preparing compositions comprising: (a) Sieving paroxetine or pharmaceutically acceptable salts thereof, diluent, disintegrant, sweetener, flavoring agent, are sieved separately through a 40# sieve, and lubricant separately through a 60# sieve; (b) Blending of previously sifted paroxetine hydrochloride, and diluent into the blender for 15 minutes; (c) Mixing previously sifted disintegrant, sweetener, and flavoring agent to the above blend prepared in step (b) for 10 minutes; (d) Adding lubricant to the prelubricated blend of step (c) and mix properly for 5 minutes; and (e) Compressing the resulting mixture into the tablet dosage form. Another embodiment of the present invention can effectively treat the major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder with and without agoraphobia, which is a fear of open spaces, social anxiety disorders / social phobia (SAD), generalised anxiety disorder, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). Objects of the Invention The primary object of the present invention is to provide an orally disintegrating tablet of Paroxetine or pharmaceutically acceptable salts thereof. Another object of the present invention is to provide a therapeutically effective amount of Paroxetine or pharmaceutically acceptable salts thereof, sodium starch glycolate, dibasic calcium phosphate dihydrate, magnesium stearate, and one or more pharmaceutically acceptable excipients. Another further object of the present invention is to enhance the disintegration and dissolution of the drug for oral administration. A further object of the present invention is to provide a stable orally disintegrating tablet of Paroxetine or pharmaceutically acceptable salts thereof. Yet another object of the present invention is to provide a treatment that is effective and very convenient for administration without the need for water or swallowing difficulties, which will improve patient compliance. Detailed description of the Invention The present invention is understood more readily by reading the following detailed description of the invention and by studying the included examples. The term "Orally disintegrating tablet” refers to a solid dosage form of the present invention, which disintegrates rapidly in the oral cavity of a patient after administration, without chewing. The term “pharmaceutically acceptable salt” refers to a salt of a compound that is derived from a variety of physiologically acceptable organic and inorganic counter ions. Such counter ions are well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, aluminum, lithium and ammonium, for example tetraalkylammonium, and the like when the molecule contains an acidic functionality; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, sulfate, phosphate, diphosphate, nitrate hydrobromide, tartrate, mesylate, acetate, malate, maleate, fumarate, tartrate, succinate, citrate, lactate, pamoate, salicylate, stearate, methanesulfonate, p-toluenesulfonate, and oxalate, and the like. As per the present invention, paroxetine is in the form of paroxetine hydrochloride. The term “about” is used herein to mean approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about", as and when used in this specification, means ±10 % of the mentioned value. The term “% w / w” is intended to mean the percentage of an ingredient(s) / the total percentage by weight of the composition (100%). Here the % w / w is to be calculated against the total weight of the composition. The main embodiment of the present invention is an orally disintegrating tablet comprised of Paroxetine or pharmaceutically acceptable salts thereof, at least one disintegrant and diluent. In addition, the orally disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from a sweetener, flavoring agent, and lubricant. As per one embodiment of the present invention Paroxetine or pharmaceutically acceptable salts thereof, is present in the range of about 0.5 %w / w to about 40 %w / w, preferably in the range of about 2 %w / w to about 20 %w / w. The D50 particle size of Paroxetine or a pharmaceutically acceptable salt thereof is less than 70 pm, more preferably less than 40 pm. As per one embodiment of the present invention, a suitable diluent for the present invention is selected from the group consisting of dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, calcium carbonate, magnesium carbonate, kaolin, spray dried or anhydrous lactose, microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol, maltodextrin, powdered sugar, compressible sugar, sucrose, dextrose, inositol or any combinations thereof. In the present invention, the dibasic calcium phosphate dihydrate is preferred as a diluent in the range of about 50 %w / w to about 95 %w / w, preferably in the range from about 60 %w / w to about 90 %w / w and comprises coarser particles and fine particles. Dibasic calcium phosphate dihydrate is an inorganic mineral and pharmaceutical excipient that is chemically composed of calcium ions (Ca2+) and phosphate anions. It is also known as calcium hydrogen phosphate dihydrate, calcium hydrogen orthophosphate dihydrate, calcium monohydrogen phosphate dihydrate, and dicalcium orthophosphate. Dibasic calcium phosphate dihydrate does not absorb moisture from the environment and remains stable at ambient conditions. It has very good compaction and flow properties as well as low lubricant sensitivity. The share of elastic recovery is minimal for dibasic calcium phosphate dihydrate. This means that it is nearly free of elastic recovery and tablets made from it will not regain size after compression. Thus, such tablets show a lower tendency towards capping and lamination. Therefore, dibasic calcium phosphate dihydrate is an ideal diluent for orally disintegrating tablets of Paroxetine Hemihydrate Hydrochloride. As per one another embodiment of the present invention, a suitable disintegrant for the present invention is selected from a group consisting of methylcellulose, alginic acid, guar gum, carboxymethylcellulose calcium, polacrilin potassium, croscarmellose sodium, carmellose calcium, crospovidone, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sodium carboxymethyl starch, poloxamer, magnesium aluminum silicate, sodium starch glycolate, and sodium alginate or any combination thereof. Sodium Starch glycolate is the preferred disintegrant for the present invention in the range from about 0.1 %w / w to about 15 %w / w, preferably in the range from about 0.5 %w / w to about 10 %w / w. Sodium starch glycolate has excellent hydration capacity, flow properties, and rapid water absorption, which causes significant swelling and a notable increase in the volume of granules. As a result, the tablets disintegrate rapidly and uniformly. Therefore, sodium starch glycolate is an ideal disintegrant for orally disintegrating tablets of Paroxetine Hemihydrate Hydrochloride. As per one more embodiment of the present invention, a suitable lubricant is selected from the group consisting of boric acid, magnesium stearate, sodium stearyl fumarate, micronized polyoxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or any combination thereof. Magnesium stearate is preferred as a lubricant for the present invention and is present in the range from about 0.1 %w / w to about 25 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w, wherein the ratio of magnesium stearate to dibasic calcium phosphate dihydrate is 1:50 to 1:99 preferably in the range of about 1:70 to 1:95. As per another embodiment of the present invention, at least one further pharmaceutically acceptable excipient is a sweetener selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or any combination thereof. Sodium saccharin is preferred as a sweetener for the present invention and is present in the range of about 0.05 %w / w to about 20 %w / w, preferably in the range of about 0.1 %w / w to about 10 %w / w. As per one another embodiment of the present invention, a flavoring agent is selected from a group consisting of menthol, floral fennel flavor, mint powder, vanillin, orange flavor, or any combinations thereof. The orange flavor is preferred as a flavoring agent present in the range from about 0.1 %w / w to about 20 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w. In the preferred embodiment, the present invention has been made to solve the abovementioned problems, and its object is to use Paroxetine or a pharmaceutically acceptable salt thereof as an active ingredient, which provides a faster disintegration time and faster dissolution rate. Paroxetine is used for the treatment or prevention of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder with and without agoraphobia, which is a fear of open spaces, social anxiety disorders / social phobia (SAD), generalized anxiety disorder, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD) and very convenient for administration without the problem of swallowing and using water thereby increasing patient compliance. As per one embodiment of the present invention, the orally disintegrating tablet comprising selective serotonin-reuptake inhibitors (SSRIs) or pharmaceutically acceptable salts thereof, present in an amount from about 0.5 %w / w to about 40 %w / w, preferably in the range of about 2 %w / w to about 20 %w / w, a diluent is present in the range of about 50 %w / w to about 95 %w / w, preferably in the range from about 60 %w / w to about 90 %w / w, a disintegrant is present in the range from about 0.1 %w / w to about 15 %w / w, preferably in the range from about 0.5 %w / w to about 10 %w / w, lubricant is present in the range from about 0.1 %w / w to about 25 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w, the sweetener is present in the range of about 0.05 %w / w to about 20 %w / w, preferably in the range of about 0.1 %w / w to about 10 %w / w and the flavoring agent is present in the range from about 0.1 %w / w to about 20 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w. As per one preferred embodiment of the present invention comprising Paroxetine or pharmaceutically acceptable salts thereof, present in an amount from about 0.5 %w / w to about 40% w / w, preferably in the range of about 2 %w / w to about 20 %w / w, dibasic calcium phosphate dihydrate is present in the range from about 50 %w / w to about 95 %w / w, preferably from about 60 %w / w to about 90 %w / w, sodium starch glycolate is present in the range from about 0.1 %w / w to about 15 %w / w, preferably in the range from about 0.5 %w / w to about 10 %w / w, magnesium stearate is present in the range from about 0.1 %w / w to about 25 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w, sodium saccharin is present in the range of about 0.05 %w / w to about 20 %w / w, preferably in the range of about 0.1 %w / w to about 10 %w / w and the orange flavor is present in the range from about 0.1 %w / w to about 20 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w. As per one more embodiment of the present invention, the ratio of lubricant to diluent is 1:50 to 1:99 preferably in the range of about 1:70 to 1:95. The ratio of magnesium stearate to dibasic calcium phosphate dihydrate is 1:50 to 1:99 preferably in the range of about 1:70 to 1:95. Another embodiment of the present invention is to manufacture an orally disintegrating tablet containing Paroxetine by direct compression method, which is one of the most economical methods. This method is particularly suitable for providing high-strength, low-breakage tablets comprising relatively high concentrations on a scale suitable for commercial production. As per one another embodiment of the present invention, the disintegrating time of the Paroxetine orally disintegrating tablet is less than 3 minutes, preferably less than 2 minutes. As per another embodiment of the present invention, 85 % of the Paroxetine is released in 80 minutes, preferably more than 85 % is released within 60 minutes. As per one embodiment of the present invention, packaging material for an orally disintegrating tablet of Paroxetine is selected from the Polypropylene Bottle with Silica canister, PP Bottle with an Oxygen scavenger, HDPE Bottle, HDPE Bottle with SAF, HDPE Bottle with CR cap, HDPE Bottle with Silica canister, HDPE Bottle with an Oxygen scavenger, Alu-Alu Blister and PVC / PVDC-Alu Film. In the present invention, the Alu-Alu blister or HDPE Bottle with CR cap containing silica canister is preferred as packaging material to deliver the desired physicochemical parameters. As per one more embodiment, the direct compression method is used to prepare the orally disintegrating tablet. Paroxetine hydrochloride hemihydrate, dibasic calcium phosphate dihydrate, sodium starch glycolate, sodium saccharin, and orange flavor are sieved separately through a 40# sieve. Magnesium stearate is sieved separately through a 60# sieve. The previously sifted Paroxetine hydrochloride hemihydrate and dibasic calcium phosphate dihydrate were loaded into the blender and mixed for 15 minutes. After that, previously sifted sodium starch glycolate, sodium saccharin, and orange flavor are blended with the above blend and mixed for 10 minutes. At last, the previously sifted magnesium stearate is added to the above mixture and blended for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in Alu-Alu blister or HDPE Bottle with CR cap containing silica canister preferred as packaging materials to deliver the desired physicochemical parameters. The invention is further illustrated by the following examples, which are by no means intended to limit the scope of the invention but are given by way of illustration. Example 1 The orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in Table I for a dose strength of 20 mg: TABLE-I Ingredients Paroxetine Hydrochloride Hemihydrate 6.51 Lactose 89.64 Sodium starch glycolate 1.70 Sodium saccharin 0.71 Orange Flavour 1.14 Magnesium Stearate 0.28 Total 100.00 Manufacturing process: Paroxetine hydrochloride hemihydrate, lactose, sodium starch glycolate, sodium saccharin, and orange flavor are sieved separately through a 40# sieve. Magnesium stearate is sieved separately through a 60# sieve. The previously sifted Paroxetine hydrochloride hemihydrate and lactose were loaded into the blender and mixed for 15 minutes. After that, previously sifted sodium starch glycolate, sodium saccharin, and orange flavor are blended with the above blend and mixed for 10 minutes. At last, the previously sifted magnesium stearate is added to the above mixture and blended for 5 minutes. Observation: The blend flow was not good so, further compression activity was not performed. To optimize blend flow, it was necessary to change the diluent. Test Parameters of blend Result Bulk Density (gm / ml) 0.385 Tap Density (gm / ml) 0.512 Carr Index (%) 24.80 Hausner Ratio 1.33 Example 2 The orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in Table II for a dose strength of 20 mg: TABLE-II Ingredients Paroxetine Hydrochloride Hemihydrate 6.51 Dibasic calcium phosphate dihydrate 89.64 Sodium starch glycolate 1.70 Sodium saccharin 0.71 Orange Flavour 1.14 Magnesium Stearate 0.28 Total 100.00 Manufacturing process: Paroxetine hydrochloride hemihydrate, dibasic calcium phosphate dihydrate, sodium starch glycolate, sodium saccharin, and orange flavor are sieved separately through a 40# sieve. Magnesium stearate is sieved separately through a 60# sieve. The previously sifted Paroxetine hydrochloride hemihydrate and dibasic calcium phosphate dihydrate were loaded into the blender and mixed for 15 minutes. After that, previously sifted sodium starch glycolate, sodium saccharin, and orange flavor are blended with the above blend and mixed for 10 minutes. At last, the previously sifted magnesium stearate is added to the above mixture and blended for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. Observation: A sticking problem was observed during compression. To optimize the sticking problem, it was necessary to increase the concentration of Lubricant. Test Parameters of blend Result Bulk Density (gm / ml) 0.432 Tap Density (gm / ml) 0.569 Carr Index (%) 24.07 Hausner Ratio 1.32 Example 3 The orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in Table III for a different dose strength of 20 mg: TABLE-III Ingredients Paroxetine Hydrochloride Hemihydrate 6.51 Dibasic calcium phosphate dihydrate 88.92 Sodium starch glycolate 1.70 Sodium saccharin 0.71 Orange Flavour 1.14 Magnesium Stearate 1.00 Total 100.00 Manufacturing process: Paroxetine hydrochloride hemihydrate, dibasic calcium phosphate dihydrate, sodium starch glycolate, sodium saccharin, and orange flavor are sieved separately through a 40# sieve. Magnesium stearate is sieved separately through a 60# sieve. The previously sifted Paroxetine hydrochloride hemihydrate and dibasic calcium phosphate dihydrate were loaded into the blender and mixed for 15 minutes. After that, previously sifted sodium starch glycolate, sodium saccharin, and orange flavor are blended with the above blend and mixed for 10 minutes. At last, the previously sifted magnesium stearate is added to the above mixture and blended for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in an Alu-Alu blister or HDPE Bottle with a CR cap containing silica canister preferred as packaging materials to deliver the desired physicochemical parameters. Observation: All the physical and chemical parameters of the tablets were found satisfactory. Test Parameters of blend Result Bulk Density (gm / ml) 0.440 Tap Density (gm / ml) 0.610 Carr Index (%) 27.87 Hausner Ratio 1.38 Example 4 The Dissolution profile of the tablet prepared according to example 3 The conditions of dissolution are the following: Apparatus: USP type II (paddle) Rate of rotation: 50 RPM Volume: 900ml Temperature: 37°C ± 0.5°C Detection: High-performance liquid chromatography equipped with UV / PDA at 295 nm. Dissolution medium: 0.1 N HC1, The orally disintegrating tablet of Paroxetine was tested for its dissolution profile measured in 900 mL of 0.1 N HC1, at 50 RPM in USP II (Paddle) apparatus, and the active ingredient of the tablet released more than 95% in 60 minutes. Example 5 The tablet prepared according to example 3 were subjected to a stability study of 25°C / 60% RH and 40°C / 75% RH for 1 month. Results are tabulated below. Paroxetine 20 mg orally disintegrating tablet Tesf Specification IIIHilliil (Initial) Exp 3 (After I month) Exp 3 (After 3 months) 25°C / 60% nit Kn 40°C / llliilB Kn 25^ / iiiiBii Krl 40°C / iiiiBii DU Kn Hardness 20N-70N 49 N 52N 48 N 50N 48N Average weight 350 mg ± 5% (332.5mg-367.5mg) 349.50 350.88 350.45 350.51 349.98 Thickness 2.90mm     ± 0.3mm (2.6mm-3.2mm) 2.92 2.90 2.89 2.91 2.90 Disintegration Not more than 3 minutes 22sec 30sec 29sec 32sec 28sec Assay (%) 95.0% - 105.0% of the labelled amount of Paroxetine, (as paroxetine hemihydrate hydrochloride) 100.8 98.53 99.40 100.2 100.9 Test Specification ii^ (Initial) Exp 3 (After 1 month) Exp 3 (After 3 months) 25°C / 60% RH 40°C / I iiM RH 25°C / IB iiiiiB 40°C / RH Dissolution NLT 75% (Q) labelled amount of Paroxetine should be dissolve in 45 minutes. 95.6 92.9 93.5 94.9 92.1 Impurities (%) Unknown impurity Not more than 0.2% 0.0126 0.066 0.05 0.079 0.1094 Total impurity Not more than 0.5% 0.0126 0.066 0.05 0.079 0.1094

Claims

1. An Orally rapidly disintegrating tablet of paroxetine for oral administration comprising:a) paroxetine or pharmaceutically acceptable salts thereof, is present in an amount ranging from about 0.5 %w / w to about 40 %w / w, preferably in the range from about 2 %w / w to about 20 %w / w;b) at least one diluent;c) at least one disintegrant is present in the range of about 0.1 %w / w to about 15 %w / w, preferably in the range of about 0.5 %w / w to about 10 %w / w;d) at least one lubricant is present in the range from about 0.1 %w / w to about 25 %w / w, preferably in the range from about 0.5 %w / w to about 15 %w / w; ande) at least one or more pharmaceutically acceptable excipients,wherein the Orally rapidly disintegrating tablet has a hardness of about 20N to about 70N.

2. The Orally rapidly disintegrating tablet according to claim 1, wherein the diluent is selected from the group consisting of dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, calcium carbonate, magnesium carbonate, kaolin, spray dried or anhydrous lactose, microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol, maltodextrin, powdered sugar, compressible sugar, sucrose, dextrose, inositol or combinations thereof3. The Orally rapidly disintegrating tablet according to claim 2, wherein the diluent is dibasic calcium phosphate dihydrate present in the range from about 50 %w / w to about 95 % w / w, preferably from about 60 %w / w to about 90 % w / w.

4. The Orally rapidly disintegrating tablet according to claim 3, wherein the dibasic calcium phosphate dihydrate comprises coarser particles and fine particles.

5. The Orally rapidly disintegrating tablet according to claim 1, wherein the disintegrant is selected from the group consisting of methylcellulose, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, polacrilin potassium, croscarmellose sodium, guar gum, poloxamer, sodium starch glycolate, and sodium alginate or any combination thereof.

6. The Orally rapidly disintegrating tablet according to claim 5, wherein the disintegrant is sodium starch glycolate.

7. The Orally rapidly disintegrating tablet according to claim 1, wherein the lubricant is selected from the group consisting of boric acid, magnesium stearate, sodium Stearyl fumarate, micronized polyoxyethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate or combinations thereof.

8. The Orally rapidly disintegrating tablet according to claim 7, wherein the lubricant is magnesium stearate.

9. The orally disintegrating tablet according to claim 1, wherein the ratio of a lubricant to the diluent is in the range of 1:50 to 1:99 preferably in the range of about 1:70 to 1:95.

10. The orally disintegrating tablet according to claim 9, wherein the ratio of magnesium stearate to dibasic calcium phosphate dihydrate is in the range of 1:50 to 1:99 preferably in the range of about 1:70 to 1:95.

11. The Orally rapidly disintegrating tablet according to claim 1, wherein one or more pharmaceutically acceptable excipients, are selected from the sweeteners and flavoring agents.

12. The Orally rapidly disintegrating tablet according to claim 11, wherein the sweetener is selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof.

13. The Orally rapidly disintegrating tablet according to claim 11, wherein the flavoring agent is selected from the group consisting of menthol, floral fennel flavor, mint powder, vanillin, or orange flavor or combinations thereof.

14. The Orally rapidly disintegrating tablet according to claim 11, further comprises sodium saccharin and orange flavor.

15. The Orally rapidly disintegrating tablet of claim 1, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

16. The Orally rapidly disintegrating tablet according to claim 1, wherein the D50 particle size of paroxetine or pharmaceutically acceptable salt thereof, is less than 70 pm, more preferably less than 40 pm.

17. The Orally rapidly disintegrating tablet according to claim 1, wherein the Orally rapidly disintegrating tablet is manufactured by the direct compression method comprising the steps of:(a) Sieving paroxetine hydrochloride hemihydrate or pharmaceutically acceptable salts thereof, dibasic calcium phosphate dihydrate, sodium starch glycolate, sodium saccharin, orange flavor is sieved separately through a 40# sieve, and magnesium stearate separately through a 60# sieve;(b) Blending of previously sifted Paroxetine hydrochloride hemihydrate and dibasic calcium phosphate dihydrate in a blender;(c) Mixing of previously sifted sodium starch glycolate, sodium saccharin, and orange flavor to the above blend;(d) Adding previously sifted magnesium stearate to the above mixture of step (c) and blend in a blender;(e) Compressing the lubricated mixture into the tablet dosage form; and(f) Packing of the tablet into an Alu-Alu blister or HDPE Bottle with CR cap containing silica canister.

18. The Orally rapidly disintegrating tablet according to claim 1, wherein the Orally rapidly disintegrating tablet is disintegrated upon contact with saliva in less than 3 minutes, preferably less than 2 minutes.

19. The Orally rapidly disintegrating tablet according to claim 1, wherein 85 % of the paroxetine or pharmaceutically acceptable salts thereof, is released within 80 minutes, preferably more than 85 % is released within 60 minutes.

20. The Orally rapidly disintegrating tablet according to claim 1, is used for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder with and without agoraphobia, which is a fear of open spaces, social anxiety disorders / social phobia (SAD), generalised anxiety disorder, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD).

21. The Orally rapidly disintegrating tablet according to claim 1, wherein:a) 0.5 %w / w to about 40 %w / w, preferably in the range of about 2 %w / w to about 20 %w / w of paroxetine or pharmaceutically acceptable salts thereof;b) 50 %w / w to about 95 % w / w, preferably from about 60 %w / w to about 90 % w / w of dibasic calcium phosphate dihydrate;c) 0.1 %w / w to about 15 %w / w, preferably in the range of about 0.5 %w / w to about 10 %w / w of sodium starch glycolate;d) 0.1 %w / w to about 25 %w / w, preferably in the range from about 0.5 %w / w to about 15% w / w of magnesium stearate;e) 0.05 %w / w to about 20 %w / w, preferably in the range of about 0.1 %w / w to about10 % w / w of sodium saccharin; andf) 0.1 %w / w to about 20 %w / w, preferably in the range from about 0.5 % w / w to about 15 % w / w of orange flavor.