Title of Invention

A NOVEL PROCESS OF PREPARATION OF MOUTH DISPERSIBLE TABLET OF ONDANSETRONE HCL DIHYDRATE

Abstract

A novel process of preparing a mouth dispersible ondansetrone Hcl dihydrate tablet comprising the following steps, Mixing an active ingredients of ondansetrone Hcl dihydrate 5 mg / unit dose , with other excipients like sweetening agent lactose 634 mg / unit dose , starch 164.5 mg/ Unit dose, aspartame 8 mg /unit dose , and sodium saccharine 6 mg /unit dose; flavourants 13.5 mg /unit dose ; free soluble compound anhydrous dextrose 20 mg/unit dose , and lactose ; paste of starch and polyvinyl pyrrolidine K-30 12 mg / unit dose as binder and followed by granulating and lubricating .

Full Text

FORM-2 THE PATENTS ACT, 1970 COMPLETE SPECIFICATION [SECTION 10] 1. A NOVEL PROCESS OF PREPARATION OF MOUTH DISPERSIBLE TABLET OF ONDANSETRONE HCl DIHYDRATE. 2. (a) SKYMAX LABORATORIES PVT LTD., (b) Plot No. G/1445-46, Lodhika G.I.D.C., Matoda-360035, Dist. Rajkot. Gujarat State, India. (c) Indian. The following specification particularly describes and ascertains the nature of the invention and the manner in which it is to be performed. ORGN Granted The present invention relates to A novel process of preparation of mouth dispersible tablet of Ondansetrone HC1 dihydrate. The present invention provides a novel process of preparation of mouth dispersible tablet of Ondansetrone HC1 dihydrate for oral administration. For oral administration mouth dispersible tablet is more suitable way than swallowing tablets. Generally formulations for oral administration are tablets/lozenges, capsules, granules, powders, solutions, syrups etc. Ondansetrone HC1 dihydrate mouth dispersible tablets are formulated for oral administration gives antiemetic effect. Ondansetrone HC1 dihydrate (C18H19N3OHCl2H2O) is highly selective potent 5-HydroxyTryptamine-receptor antagonist at subtype 3 (5HT3). The said active component Ondansetrone blocks 5HT3 receptors in brain and give antiemetic effect. Ondansetrone is centrally acting drug. In very shorter time it reaches to the brain and start its antiemetic action, which gives symptomatic relief from nausea and vomiting. It is prophylactic against vomiting and nausea associated with Radiotherapy, Chemotherapy. At present Ondansetrone HC1 dihydrate tablet is available as film coated tablet for oral use. Film coating on tablet masks the unpleasant taste of ondansetrone. Ondansetrone is also available in syrup and injection form. Patient finds discomfort with intake of Ondansetrone HC1 in the form of film coated tablet, syrup and injection. Film coated tablet is swallowed as it is, film of the tablet breaks in stomach and tablet get dispersed/dissolved in gastric secretion and then absorption of drug will start. Which takes more time to onset of action of drug. Generally film coated Ondansetrone HCl dihydrate tablets are manufactured by simple wet & dry granulation process. Prepared granules are coated by spraying coating solution, which is made by using HydroxyPropyl Methyl Cellulose (HPMC), Plasticizer, colour, Titanium Dioxide, Water, IPA, Methylene Chloride etc. as per standard methods. Tablets are loaded in coating pan & uniform films are coated on all tablets. Coated tablets are packed in aluminium strip & sealed under controlled temperature & humidity. This ensures that the product (tablet) will remain stable until utilized by the consumer. Generally film coated Ondansetrone HCl dihydrate tablets are swallowing tablets and are not liked by Children, Senior Citizens & other patients, because of difficulty in swallowing. However, Film coating on it masks its bitter taste. Those patients complaining conditions like severe vomiting and nausea do not able to swallow the tablet. In severe cases film coated swallowing tablet comes out as it is due to vomiting. To control severe condition of nausea and vomiting, patients are treated with injections. However, it is inconvenient to give parental dose at any time, anywhere. To overcome the discomforts raised by the parental administration of Ondansetrone HCl dihydrate injection and/or oral administration of Ondansetrone HCl film coated tablet, a novel process is developed to prepare mouth dispersible tablet Ondansetrone HCl dihydrate. To avoid the bitter taste of film coated swallowing tablet and comparatively slow onset of action, a novel process of preparation of mouth dispersible tablet of Ondansetrone HCl dihydrate have confronted with two problems-suppression of bitter taste of tablet and the rapid disintegration of tablet in saliva in oral cavity, therefore fast onset of action, A novel process by which mouth dispersible tablet of Ondansetrone HCl dihydrate developed provides fast disintegration in mouth without water for ease in oral administration. Prepared mouth dispersible tablet is uncoated tablet, containing sweeteners and flavourants to mask the bitter taste of the drug; fast disintegrating agent sodium starch Glycolate and freely soluble compound anhydrous dextrose and lactose for faster and easy dispersion of tablet in saliva of mouth cavity. Present Invention of a novel process of preparing mouth dispersible tablet of Ondansetrone HCl dihydrate aid the patient to get fast symptomatic relief from vomiting and nausea sensation within very short time due to fast dispersion of active ingredient Ondansetrone HCl dihydrate in saliva of sublingual cavity after placing it in mouth. Fastest sublingual absorption of drug and temperature of oral cavity, tablet gets easily disperse in mouth and immediately circulated in blood. Mouth dispersible tablet formulation of Ondansetrone HC1 dihydrate is the most preferred & provide fixed dose for patient who find difficulty in swallowing tablets. In the present invention, each mouth dispersible tablet of Ondansetrone HC1 dihydrate contains volume of Ondansetrone drug is 4 mg per unit dose, Unit dose of tablet is preferably advisable to intake once in a day, which is vary on the severity of the symptomatic condition. The tablet of Ondansetrone HC1 dihydrate prepared by novel process gives synergistic effect, in very short time after reaching to the brain and starts its antiemetic action, symptomatic relief from nausea and vomiting. The novel process for the preparation of mouth dispersible tablet of Ondansetrone HC1 dihydrate is given below. Step 1: Granules production by using active & inactive ingredients. The Ondansetrone Hydrochloride dihydrate is an active ingredient & 5HydroxyTryptamine subtype 3 receptor antagonist, 5 mg/unit dose of it was mixed with physiologically acceptable excepients: sweetening agents 634 mg/unit dose of Lactose, 164.5 mg/unit dose of Starch and 8 mg/unit dose of Aspartame, which was further admixed with 13.5 mg/unit dose of flavourants and 20 mg/unit dose anhydrous dextrose. This mixture of above active & inactive ingredients was kept for 25 to 30 minute for better mixing. A paste was prepared and used for binding the whole above mass. The paste was prepared by using starch and 12-mg/unit dose of Polyvinylpyrrolidone K-30 in boiling purified water. Procedure for paste preparation: Polyvinylpyrrolidone K-30 added in boiling water and stirred it still it completely dissolved. Starch slurry was added in boiling solution. Gently mixed the poiling-solution and uniform paste was prepared. This paste was cooled at room temperature and admixed with the above mass for 2 to 5 minutes and passed through granulation process. Granules were obtained by passing the paste of wet mass through 16 # sieve. Granules were collected in tray and dry for 4 hours at 50° C or still completely dry. Formulated dry granules were further passed through 20 # sieve for fine granules. These granules were packed in double layer polyethylene bag. Step-2: Lubrication and Flavouring of Granules. Granules obtained from the above step-1 were admixed with lubricants like 5 mg/unit dose of magnesium stearate, 9 mg/unit dose of talcum, 4 mg/unit dose of Cab-O-Sil etc. These granules were further added with fast disintegrating agent 10 mg/unit dose of sodium starch glycolate and sweetener 6 mg/unit dose of sodium saccharine. Smooth granules prepared were flavoured by adding tasteful flavouring agent and kept for 5 minutes. These granules were collected in double layer polyethylene bag. Step-3: Compression of Granules & formulation of tablet The granulated material of step-2 was compressed into tablets under maintained temperature & humidity control. These tablets were preserved by packing in polyethylene bag. These tablets are packed under blister or Aluminium strip. For the preparation of mouth dispersible tablet according to the present invention requires active and inactive ingredients and other excipients, conventional to the art such as binders, lubricants, disintegrating agents, sweetening agents and flavourants, free soluble compound. Sweetening agents Lactose, Aspartame and Sodium Saccharine were used in the present invention to impart its delicious taste into tablet and mask bitter taste of active ingredient Ondansetrone. The paste prepared of Polyvinylpyrrolidone (PVP) K-30 binder and starch, to bind the whole mass of active and inactive ingredients during granulation process in tablet formulation. Lubricants magnesium stearate, talcum, Cab-O-Sil were used to give smoothness to tablets. Flavourant was to impart its taste. Fast disintegrating agent sodium starch Glycolate, which gives easy and faster dispersion of tablet in saliva of mouth cavity. Anhydrous dextrose and lactose were used in the process are rapid soluble agent, helps in fast and freely soluble of tablet in oral cavity when placed on tongue. All these ingredients were added as per the stability of the tablet & taste requirement. It is important that the final product should have a high degree of stability. Ondansetrone HCI dihydrate is bitter in taste. It is difficult to mask its bitter taste. In the preparation of novel mouth dispersible tablet of Ondansetrone HCI dihydrate, Ondansetrone drug is granulated with the other excipients and then subjected to drying, provide more stable form of tablet. Novel mouth dispersible tablet of Ondansetrone HCI dihydrate thus prepared using novel process, rapidly disperse in mouth giving sweeter taste and fast onset of action. We claim, 1. A novel process of preparing a mouth dispersible ondansetrone Hcl dihydrate tablet comprising the following steps, Mixing an active ingredients of ondansetrone Hcl dihydrate 5 mg / unit dose , with other excipients like sweetening agent lactose 634 mg / unit dose , starch 164.5 mg/ Unit dose, aspartame 8 mg /unit dose , and sodium saccharine 6 mg /unit dose; flavourants 13.5 mg /unit dose ; free soluble compound anhydrous dextrose 20 mg/unit dose , and lactose ; paste of starch and polyvinyl pyrrolidine K-30 12 mg / unit dose as binder and followed by granulating and lubricating . 2 . A novel process for preparing a mouth dispersible ondansetrone Hcl dihydrate tablet as claimed in claim 1 , wherein lubricating the granules using magnesium stearate 5 mg /unit dose , talcum 9 mg / unit dose , Cab - sill 4 mg / unit dose ; Disintegrate sodium starch Glycol ate 10 mg / unit dose ; and sweetener sodium saccharine 6 mg / unit dose and flavour ants 13.5 mg / unit dose into wet -dry granules of Ondansetrone Hcl dihydrate as per the taste and nature of the tablet. 3- A novel process of preparing a mouth dispersible Ondansetrone HCl dihydrate tablet as claimed in claim 1, wherein Ondansetrone HCl dihydrate 5 rag/unit dose is admixed with aspartame 8 mg/unit dose and dry fiavourants 13.5 mg/unit dose to mask the bitter taste of it, during wet granulation; also admixing anhydrous dextrose 20 mg/unit dose and lactose 634 mg/unit dose. 4 A novel process of preparing of a mouth dispersible Ondansetrone HCl dihydrate tablet as claimed in claims 1 to 4 such as herein described with reference to a description. Dated this on 16th of April 2003.

Documents:

393-mum-2003-cancelled page-(9-10-2003).pdf

393-mum-2003-claim(granted)-(9-10-2003).pdf

393-mum-2003-claims(granted)-(9-10-2003).doc

393-mum-2003-correspondence(9-10-2003).pdf

393-mum-2003-correspondence(ipo)-(23-04-2003).pdf

393-mum-2003-form 1(21-04-2003).pdf

393-mum-2003-form 19(11-6-2003).pdf

393-mum-2003-form 2(granted)-(21-04-2003).pdf

393-mum-2003-form 2(granted)-(9-10-2003).doc

393-mum-2003-form 26(5-3-2003).pdf

393-mum-2003-form 3(21-4-2003).pdf

393-mum-2003-form 5(21-4-2003).pdf