Orally Disintegrating Tablets

Abstract

The present invention describes a directly compressible composite prepared by co-processing a water-soluble excipient and calcium silicate. The present invention further describes the incorporation of the co-processed composite into a tablet formulation. The orally disintegrating tablets are of optimal mechanical strength and disintegrate within 60 seconds in the oral cavity.

1 . A directly compressible composite for an orally disintegrating tablet comprising at least one water-soluble excipient and calcium silicate prepared by co-processing. 
   
   
       2 . A directly compressible composite as claimed in  claim 1 , wherein the water soluble excipient is a carbohydrate, a water soluble salt or a polyhydric alcohol or its derivative. 
   
   
       3 . A directly compressible composite as claimed in  claim 2 , wherein the water soluble carbohydrate is a monosaccharide, disaccharide, oligosaccharide or polysaccharide. 
   
   
       4 . A directly compressible composite as claimed in  claim 3 , wherein the monosaccharide is xylose, glucose, mannose, fructose, galactose, and sorbitol. 
   
   
       5 . A directly compressible composite as claimed in  claim 3 , wherein the disaccharide is maltose, lactose, cellobiose, sucrose, mannitol and trehalose. 
   
   
       6 . A directly compressible composite as claimed in  claim 3 , wherein the oligosaccharide is raffinose and dextrates. 
   
   
       7 . A directly compressible composite as claimed in  claim 3 , wherein the polysaccharide is maltodextrins. 
   
   
       8 . A directly compressible composite as claimed in  claim 2 , wherein the water soluble salt is sodium chloride. 
   
   
       9 . A directly compressible composite as claimed in  claim 2 , wherein the water soluble polyhydric alcohol is propylene glycol, polyethylene glycol and glycerin. 
   
   
       10 . A directly compressible composite as claimed in  claim 1 , wherein calcium silicate has an aspect ratio of about 1:1 to about 2.5:1 and an oil absorption of from about 20 ml/100 gm to 220 ml/100 gm. 
   
   
       11 . A directly compressible composite as claimed in  claim 1  wherein the ratio of at least one water-soluble excipient and calcium silicate is from about 50:1 to about 1:50. 
   
   
       12 . A directly compressible composite as claimed in  claim 1  wherein the ratio of at least one water-soluble excipient and calcium silicate is preferably from about 30:1 to about 1:30 and more preferably from about 20:1 to about 1:20. 
   
   
       13 . A directly compressible composite as claimed in  claim 1  wherein the composite has not less than 40% of particles less than 150 microns. 
   
   
       14 . A directly compressible composite as claimed in  claim 1  wherein the composite has loss on drying of less than 2% w/w. 
   
   
       15 . A directly compressible composite as claimed in  claim 1  wherein the composite has porosity of at least about 50%. 
   
   
       16 . A method for producing a directly compressible composite as claimed in  claim 1 , wherein co-processing involves processes such as physical mixing, wet mixing, complexation, precipitation, spray drying, lyophilization, microencapsulation, spray congealing, hot melt, gas antisolvent or rapid evaporation of supercritical solvent methods employed with supercritical fluid processing. 
   
   
       17 . A method for producing a directly compressible composite as claimed in  claim 1 , wherein co-processing involves spray drying. 
   
   
       18 . A method for producing a directly compressible composite as claimed in  claim 1 , wherein the spray drying method comprises:
 a. Dissolving the water soluble excipient in water.   b. Adding calcium silicate with stirring to solution of step-a.   c. Homogenising the blend to make it uniform.   d. Drying the mixture in an air stream,   e. Forming the co-processed excipient.   
   
   
       19 . A method for producing a directly compressible composite wherein the spray drying method comprises:
 a. Dissolving mannitol in water.   b. Adding calcium silicate under stirring to solution of step-a.   c. Homogenising the blend to make it uniform.   d. Drying the mixture in an air stream,   e. Forming the co-processed excipient.   
   
   
       20 . An orally disintegrating tablet formulation having optimal mechanical strength comprising
 a. at least one pharmaceutically active ingredient or a nutraceutical agent   b. composites produced by co-processing of at least one water soluble excipient and calcium silicate.   c. At least one other excipient.   
     such that the tablet has optimal mechanical strength and a disintegration time of about 60 seconds in the oral cavity, 
   
   
       21 . An orally disintegrating tablet as claimed in  claim 20 , wherein the active ingredient is selected from gastrointestinal function conditioning agents anti-inflammatory agents, including, but not limited to aceclofenac, ibuprofen, diclofenac, flubiprofen, piroxicam, sulindac, and celecoxib; analgesics, including, but not limited to acetaminophen, fentanyl, tramadol and aspirin; agents for erectile dysfunction therapy, including, but not limited to sildenafil and apomorphine; anti-migraines, including, but not limited to sumatriptan, rizatriptan, zolmitriptan, naratriptan and ergotamin; antihistaminic agents, including, but not limited to loratadine, fexofenadine, pseudoephedrine and cetirizine; cardiovascular agents, including, but not limited to nitroglycerine and isosorbide dinitrate; diuretics, including, but not limited to furocemide and spironolactone; anti-hypertensive agents, including, but not limited to propranolol, amlodipine, felodipine, nifedipine, captoprile, ramiprile, atenolol, and diltiazem; anti-hypolipidemic agents, including, but not limited to simvistatin, atrovastatin, and pravastatin; anti-ulcer agents, including, but not limited to cimietidine, ranitidine, famotidine, omeprazole, esomeprazole, rabeprazole and lansoprazol; anti emetics, including, but not limited to meclizine hydrochloride, ondansetron, granisetron, ramosetron, and tropisetron; anticoagulants such as ticlopidine hydrochloride, dicumarol, or warfarin potassium; antiepileptics such as phenyloin sodium, and lamotrigine, anti-asthmatic agents, including, but not limited to aminophylline, theophylline, terbuttaline, fenoterol, formoterol, and ketotifen; brain metabolism altering drugs such as meclofenoxate hydrochloride; minor tranquilizers such as oxazolam, diazepam, clonazepam, clotiazepam, medazepam, temazepam, fludiazepam, nitrazepam, alprazolam, lorazepam or chlordiazepoxide; anti-depressants, including, but not limited to fluoxetine, mirtazepine, escitalopram and sertraline; drugs for treatment of parkinson's disease or restless leg syndrome such as ropinirole hydrochloride; drug for alzheimer's disease such as memantine; drugs for schizophrenia such as risperidone, olanzepine and aripiprazole; oral antibacterial and antifungal agents such as penicillin, ampicillin, amoxicillin, cephalexin, erythromycin ethylsuccinate, acampicillin hydrochloride, minocycline hydrochloride, chloramphenicol, tetracycline, erythromycin, fluconazole, itraconazole, ketoconazole, miconazole or terbinafine; synthetic antibacterial agents such as nalidixic acid, piromidic acid, pipemidic acid trihydrate, enoxacin, cinoxacin, ofloxacin, norfloxacin, ciprofloxacin hydrochloride, or sulfamethoxazole trimethoprim; antipasmodics such as propantheline bromide, atropine sulfate, oxapium bromide, timepidium bromide, antitussive, anti-asthmatic agents; muscle relaxants such as chlorphenesin carbamate, tolperisone hydrochloride, eperisone hydrochloride, tizanidine hydrochloride, mephenesin, chlorozoxazone, phenprobamate, methocarbamol, chlormezanone, pridinol mesylate, afloqualone, baclofen, or dantrolene sodium; oral antidiabetic agents such as glibenclamide, tolbutamide, or glymidine sodium; circulatory agents such as ubidecarenone or ATP-2Na; iron preparations such as ferrous sulfate or dried ferrous sulfate; vitamins such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin A, vitamin D, vitamin E, vitamin K or folic acid; pollakiuria remedies such as flavoxate hydrochloride, oxybutynin hydrochloride, terodiline hydrochloride, or 4-diethylamino-1,1-dimethyl-2-butynyl (I)-a-cyclohexyl-oc-phenylglycolate hydrochloride; angiotensin-converting enzyme inhibitors such as enalapril maleate, anti-viral agents such as trisodium phosphonoformate, didanosine, dideoxycytidine, azido-deoxythymidine, didehydro-deoxythymidine, adefovir dipivoxil, abacavir, amprenavir, delavirdine, efavirenz, indinavir, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir or stavudine and combinations thereof. 
   
   
       22 . An orally disintegrating tablet as claimed in  claim 20 , wherein nutraceutical ingredients include agents that have a beneficial effect on human health such as coenzyme Q-10, chondroitoin, echinacea, ephedra, glucosamine, garlic, ginkgo biloba, ginseng, grape seed extract, guarana, hawthorn, herbs, kava, kola nut, lutein, St. John's wort, vinpocetine, and yohimbe and combinations thereof. 
   
   
       23 . An orally disintegrating tablet as claimed in  claim 20 , wherein excipient is selected from a group of one or more binders, disintegrants, superdisintegrants, diluents, salivating agents, surfactants, flavors, sweeteners, colorants, diluents, souring agents, suitable taste masking agents, viscosity builders, glidants or lubricants, solubilizers, and stabilizers. 
   
   
       24 . An orally disintegrating tablet as claimed in  claim 23 , wherein the super disintegrant is natural, modified or pregelatinized starch, crospovidone, croscarmellose sodium, sodium starch glycolate, low-substituted hydroxypropyl cellulose as well as effervescent disintegrating systems. 
   
   
       25 . An orally disintegrating tablet as claimed in  claim 24 , wherein the preferred super disintegrants are crospovidone and starch. 
   
   
       26 . An orally disintegrating tablet as claimed in  claim 23 , wherein the binder is starch, pregelatinized starch, cellulose derivatives, such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and carboxymethyl cellulose (CMC) and their salts. 
   
   
       27 . An orally disintegrating tablet as claimed in  claim 23 , wherein the diluent is starch, dicalcium phosphate, microcrystalline cellulose and the like. 
   
   
       28 . An orally disintegrating tablet as claimed in  claim 23 , wherein the lubricant is magnesium stearate, calcium stearate, stearic acid, talc, and sodium fumarate stearate. 
   
   
       29 . An orally disintegrating tablet as claimed in  claim 23 , wherein the glidant is selected from colloidal silica, silica gel, precipitated silica and combinations thereof. 
   
   
       30 . An orally disintegrating tablet as claimed in  claim 23 , wherein the salivating agent is micronised polyethylene glycol, sodium chloride and precipitated micronised silica. 
   
   
       31 . An orally disintegrating tablet as claimed in  claim 23 , wherein the sweetener is aspartame, stevia extract, glycyrrhiza, saccharine, saccharine sodium, acesulfame, sucralose and dipotassium glycyrrhizinate. 
   
   
       32 . An orally disintegrating tablet of  claim 20  wherein the wicking time of the tablets is less than 60 seconds 
   
   
       33 . An orally disintegrating tablet of  claim 20  wherein the lag time for mouth disintegration is less than 10 seconds 
   
   
       34 . An orally disintegrating tablet of  claim 20  wherein the disintegration time is less than 60 seconds in the oral cavity 
   
   
       35 . An orally disintegrating tablet formulation having optimal mechanical strength comprising
 a. at least one pharmaceutically active ingredient or a nutraceutical agent   b. composites produced by co-processing of mannitol and calcium silicate.   c. At least one other excipient.   
     such that the tablet has optimal mechanical strength and a disintegration time of about 60 seconds in the oral cavity,