Title of Invention

A NOVEL METHOD FOR THE PREPARATION OF MOUTH DISPERSIBLE TABLET OFACTIVE PHARMACEUTICAL SUBSTANCE ONDANSETRON HCIV1Th BETACYCLODEXTIRN

Abstract

A novel method for the preparation of mouth dispersible tablet of active pharmaceutical substance Ondansetron HC1 with Betacyclodextrin. The process comprises preparing a dry granulation of: active ingredient Ondansetrone HC1 blended with excipients like sweetening agents, flavourants, fast and free soluble compound, binder (paste of starch and PVP K-30), lubricants, disintegrant. Compressing the dry granules into tablet form and packing the tablet in polyethylene bag under controlled temperature and environmental conditions. A novel tablet disperses very fast once placed on tongue in oral cavity. Fast dispersion of tablet in saliva gives fast relief from nausea, vomiting. Its delicious taste and fast dissolving in mouth without water gives better patient compliance in severe conditions like nausea and vomiting.

Full Text

FORM - 2 THE PATENTS ACT, 1970 COMPLETE SPECIFICATION [SECTION 10] 1. AN IMPROVED METHOD FOR THE PREPARATION OF MOUTH DISPERSIBLE TABLET OF ACTIVE PHARMACEUTICAL COMPOSITION OF ONDANSETRON HO WITH BETACYCLODEXTRIN. 2. (a) SKYMAX LABORATORIES PVT LTD., (b) Plot No. G/l 445-46, Lodhika G.I.D.C., Metoda-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. The present invention relates to an improved method of preparation of mouth dispersibJe tablet of Ondansetrone HC3 with Betacvclodextrin. The present invention provides an improved process of preparation of mouth dispersible tablet of Ondansetrone HC1 with Betacyclodextrin used for oral administration to combat the relevant disease. 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 in combination with Betacyclodextrin mouth dispersible tablets are formulated for oral administration gives antiemetic effect. Ondansetrone is highly selective potent 5- HydroxyTryptamine-receptor antagonist at subtype The said active component Ondansetrone blocks 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 tablet is available as film coated tablet for oral use. Film coating on tablet masks the unpleasant taste of drug 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 in body. Generally film coated Ondansetrone HC1 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 & 3 humidity. This ensures that the product (tablet) will remain stable until utilized by the consumer. Generally film coated Ondansetrone HC1 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 HC1 injection and/or oral administration of Ondansetrone HC1 film coated tablet, a novel process is developed to prepare mouth dispersible tablet Ondansetrone HCI with Betacyclodextrin. 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 HCI have confronted 4 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. An improved process by which mouth dispersible tablet of Ondansetron HC1 with Betacyclodextrine, developed provides fast disintegration in mouth without . water for ease in oral administration. Prepared mouth dispersible tablet is uncoated tablet, containing sweeteners and dry flavourants to mask the bitter taste of the drug; fast disintegrating agent Sodium Starch Glycolate, Crosscarmellose; lubricants Magnesium stearate, talc for faster and easy dispersion of tablet in saliva of mouth cavity. Present Invention of an improved process of preparing mouth dispersible tablet of using active pharmaceutical substance Ondansetron HC1 with Betacyclodextrin aid the patient to get fast symptomatic relief from vomiting and nausea sensation within very short time due to fast dispersion of active ingredient Ondansetron IIC1 and Betacyclodextrin 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 Ondansetron HC1 with the drug Betacyclodextrin is the most preferred & provide fixed dose for patient who find difficulty in swallowing tablets. In the present invention, each mouth dispersible tablet of Ondansetron HC1 with Betacyclodextrin contains volume of Ondansetron drug is 5 mg/unit does and Betacyclodextrin 20 mg/unit dose. Unit dose of tablet is preferably advisable to intake once in a day. which is vary on the seventy of the symptomatic condition. The tablet of Ondansetrone HC1 with Betacyclodextrin prepared by improved 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 improved process for the preparation of mouth dispersible tablet of Ondansetrone HC1 with Betacyclodextrin is given below. Step 1: Granules production using active ingredients. The Ondansetron Hydrochloride 5 mg/unit dose and Betacyclodextrine 20 mg/unit dose is an active pharmaceutical ingredient. Ondansetron is 5HydroxyTryptamine subtype 3 receptor antagonist. 5 mg/unit dose of Ondansetron powder is mixed with other active ingredient powder of Betacyclodextrin 20 mg/unit dose. Isopropyl Alcohol is used as solvent for the binder. Liquid isopropyl Alcohol is dried and power obtained from it is used in the preparation of tablet. Powder of Isopropyl Alcohol 1000 ml/unit dose is mixed with the powder of Ondansetron and Betacyclodextrin. The said powder mixture is kept for drying for some time. This powder is passed through conventional granulation process. The powder is passed through 60# mesh sieve for granulation and the granules are collected in polyethylene bag. These granules are admixed with the dry flavourants 2 mg/unit dose mi sweetening agent Aspartame 2 mg/unit dose. These flavoured granules are conserved in polyethylene bag and store at below 30° C. Step-2 Base Granulation process: Powder of Starch 161.5 mg/unit dose and Lactose 634 mg/unit dose are mixed with each other for 15 minute. A starch paste is prepared and used for binding the whole above mass. The paste is prepared by using Starch 3 mg/unit dose and 12-mg/unit dose of Polyvinylpyrrolidone K-30 in purified water. The paste of Starch & PVP K-30 is used as binder to bind 7 the mass of Starch and Lactose mixture. The wet mass is dried in tray drier at 60° C for 60 minute. Procedure for paste preparation: Polyvinylpyrrolidone K-30 added in boiling water and stirred it, until it completely dissolved. Starch slurry is added in boiling solution. Gently mixed the boiling solution and uniform paste is prepared. Dried mass is passed through 30# mesh sieve for the granulation process. These granules are collected in polyethylene bag and store at below 30° C temperature. Step 3: Lubrication and Flavouring of Granules. Granules obtained from the above step-1 are mixed with the granules of step-2. Lubricants like 5 mg/unit dose of magnesium stearate, 9 mg/unit dose of talcum, are admixed with the granules. These granules are further admixed with fast disintegrating agent Sodium Starch Glycolate 10 mg/unit dose and Crosscarmellose 5 mg/unit dose. Smooth granules prepared are flavoured by adding tasteful dry flavourants 11.5 mg/unit dose and sweetening agent 5 mg/unit dose and kept for 5 minutes. These granules are collected in double layer polyethylene bag. Step-4: Compression of Granules & formulation of tablet The granules obtained from step-3 are compressed into tablet form 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 of active pharmaceutical substance Ondansetron with Betacyclodextrin according to the present invention requires other excipients, conventional to the art such as binders, lubricants, disintegrating agents, sweetening agents and dry flavourants. Sweetening agents Lactose, Aspartame and Starch are used in the present invention to impart its delicious taste into tablet and mask bitter taste of active ingredient Ondansetron. The paste prepared of binder Polyvinylpyrrolidone (PVP) K 30 and starch, to bind the whole mass of active & inactive ingredients and also during granulation process in tablet formulation. Lubricants magnesium stearate, talcum are used to give smoothness to tablets. Dry flavourant is to impart its taste. Fast disintegrating agent Sodium Starch Glycolatc, Crosscarmellose gives easy and fester dispersion of tablet in saliva 9 of mouth cavity. Lactose is used in the process is rapid soluble agent and sweetener, helps in fast and freely soluble of tablet in oral cavity when placed on tongue. All these ingredients are 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 HCl is bitter in taste. It is difficult to mask its bitter taste. In the preparation of mouth dispersible tablet of Ondansetrone HCl, Ondansetrone drug is granulated with the other excipients and then subjected to drying, provide more stable form of tablet. Mouth dispersible tablet of Ondansetrone HCl with Betacyclodextrin thus prepared using novel process, rapidly disperse in mouth giving sweeter taste and fast onset of action. We Claim, 1. An improved method for preparation of mouth dispersibie tablet of active pharmaceutical composition of Ondansetron HC1 with Betacyclodextrin comprising the steps of: (a) Preparation of granules containing active ingredients Ondansetron HC1 with Betacyclodextrin using solvent Isopropyl Alcohol and other excepients such as dry flavourants. Aspartame; (b) Preparation of granules containing inactive ingredients such as sweeteners Starch & Lactose, binder as paste ofstarch&PVP K-30; (c) Mixing the granules obtained from step-1 & step-2, further admixing lubricants Talcum & Magnesium stearate, admixing disintegrant Sodium Starch Glycolate, Crosscarmellose and dry flavourants, sweeteners; 2. An improved method of preparing mouth dispersibie tablet of active pharmaceutical substance Ondansetron HC1 with Betacyclodextrin as claimed in claim 1 consisting the mixture of: Ondansetron HC1 5 mg/unit dose; 1 Betacyclodextrine 20 mg/unit dose; Isopropyl Alcohol 1000 ml/unit dose; sweetening agents Lactose 634 mg/unit dose. Starch 161.5 mg/unit dose, Aspartame 8 mg/unit dose; Dry tlavourants 13.5 mg/unit dose; paste of Starch 3 mg/unit dose and Polyvinylpyrrolidone K-30 12 mg/unit dose as binder; lubricants magnesium stearate 5 mg/unit dose, talcum 9 mg/unit dose; disintegrating agent Sodium Starch Glycolate 10 mg/unit dose, Crosscarmellose 5 mg/unit dose . 3. An improved method of preparation of mouth dispersibic tablet of active pharmaceutical composition of Ondansetron HC1 with Betacyclodextrin as claimed in claim 1 wherein wet granules are prepared by: mixing powder of Ondansetron HC1 5 mg/unit dose with Betacyclodextrin 20 mg/unit dose, further adding powder of Isopropyl Alcohol 1000 ml/unit dose, after drying passing the mixture for the conventional granulation process using 60 # mesh sieve. Dry tlavourants 2mg/unit dose and Aspartame 8 mg/unit dose are admixing with these granules and stored below 30 C. 4. A improved method of preparation of mouth dispersible tablet of active pharmaceutical composition of Ondansetron 12 HCl with Betacyclodextrin as claimed in claim 1 comprising, mixing Starch 161.5 mg and Lactose 634 mg/unit dose and kept for 15 minutes, binding of the said mixture with the paste of starch 3 mg/unit dose and Polyvinylpyrrolidone (PVP) K-30 12 mg/unit dose, drying the wet mass at 60° C for 60 minute, preparing the granules of dried mass using conventional granulation technique using 30 # mesh sieve. 5. A improved method of preparation of mouth dispersible tablet of active pharmaceutical composition of Ondansetron HCl with Betacyclodextrin as claimed in claim 1 wherein mixing the granules obtained from step-1 & step-2, are further admixed with lubricant Talcum 9 mg/unit dose & Magnesium stearate 5 mg/unit dose, disintegrants Crosscarmellose 5 mg/unit dose & Sodium Starch Glycolate 10 mg/unit dose, dry flavourants 11.5 mg/unit dose, sweeteners. 6. A improved method for preparation of mouth dispersible tablet of pharmaceutical composition Ondansetron HCl with Betacyclodextrine as claimed in claim I to 5 substantially 14 herein described with reference to the foregoing description.

Documents:

1142-mum-2003-abstract.doc

1142-mum-2003-abstract.pdf

1142-mum-2003-cancelled pages(09-02-2004).pdf

1142-mum-2003-claims(granted)-(09-02-2004).doc

1142-mum-2003-claims(granted)-(09-02-2004).pdf

1142-mum-2003-claims.doc

1142-mum-2003-claims.pdf

1142-mum-2003-correspondence(09-02-2004).pdf

1142-mum-2003-correspondence(ipo)-(19-05-2004).pdf

1142-mum-2003-correspondence(ipo).pdf

1142-mum-2003-correspondence.pdf

1142-mum-2003-declaration certificate-(28-10-2003).pdf

1142-mum-2003-declaration.pdf

1142-mum-2003-description(granted).doc

1142-mum-2003-description(granted).pdf

1142-mum-2003-form 1(29-10-2003).pdf

1142-mum-2003-form 1.pdf

1142-mum-2003-form 19(12-12-2003).pdf

1142-mum-2003-form 19-8-dec-2003.pdf

1142-mum-2003-form 19.pdf

1142-mum-2003-form 2(09-02-2004).pdf

1142-mum-2003-form 2(cancelled) 9-feb-2004.pdf

1142-mum-2003-form 2(granted)-(09-02-2004).doc

1142-mum-2003-form 2(granted)-(09-02-2004).pdf

1142-mum-2003-form 2(granted).doc

1142-mum-2003-form 26(12-12-2003).pdf

1142-mum-2003-form 3(28-10-2003).pdf

1142-mum-2003-form 3.pdf

1142-mum-2003-form 5(28-10-2003).pdf

1142-mum-2003-form 5.pdf

1142-mum-2003-power of attorney.pdf