Disintegrating Oral Tablet Suitable For Active Pharmaceutical Ingredients

Abstract

the non-DC areas resulting in a burst of the at least one flavor ingredient upon mastication of the tablet.

1 . A disintegrating oral tablet suitable for active pharmaceutical ingredients comprising a population of particles and at least one flavor ingredient, the population of particles comprising directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles, the non-DC particles providing the tablet with a plurality of discrete non-DC areas, and the non-DC areas resulting in a burst of the at least one flavor ingredient upon mastication of the tablet. 
     
     
         2 . The oral tablet according to  claim 1 , wherein the non-DC sugar alcohol particles have not been granulated prior to tableting. 
     
     
         3 . The oral tablet according to  claim 1  or  2 , wherein the non-DC sugar alcohol particles are essentially consisting of sugar alcohol. 
     
     
         4 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are consisting of sugar alcohol. 
     
     
         5 . The oral tablet according to any of the preceding claims, wherein the tablet comprises flavor in an amount of 1-10% by weight of the tablet. 
     
     
         6 . The oral tablet according to any of the preceding claims, wherein the tablet is designed to release at least 50% by weight of the flavor within 20 seconds from onset of mastication. 
     
     
         7 . The oral tablet according to any of the preceding claims, wherein the burst of the at least one flavor ingredient involves a burst of flavors to the lungs upon mastication. 
     
     
         8 . The oral tablet according to any of the preceding claims, wherein the burst of the at least one flavor ingredient involves a burst of flavors to the nasal cavity upon mastication. 
     
     
         9 . The oral tablet according to any of the preceding claims, wherein the at least one flavor ingredient comprises a volatile flavor. 
     
     
         10 . The oral tablet according to any of the preceding claims, wherein the tablet is designed to disintegrate within 20 seconds from onset of mastication. 
     
     
         11 . The oral tablet according to any of the preceding claims, wherein the tablet obtains the burst through salivation promoted by the non-DC sugar alcohol particles during mastication in combination with a resulting dissolving of sweetener. 
     
     
         12 . The oral tablet according to any of the preceding claims, wherein the oral tablet is designed to disintegrate within 20 seconds of in vivo chewing, where the in vivo chewing is carried out by a chewing panel comprising at least 10 individuals, chewing at a rate of 60 chews per minute. 
     
     
         13 . The oral tablet according to any of the preceding claims, wherein said population of particles is tableted into a first module and combined with a second population of particles that is tableted into a second module. 
     
     
         14 . The oral tablet according to any of the preceding claims, wherein said population of particles is tableted into a first module and combined with a second population of particles that is tableted into a second module, and wherein the second module does not comprise non-DC sugar alcohol particles. 
     
     
         15 . The oral tablet according to any of the preceding claims, wherein said population of particles is tableted into a first module and combined with a second population of particles that is tableted into a second module, and wherein the second module is different in composition than the first module. 
     
     
         16 . The oral tablet according to any of the preceding claims, wherein said population of particles is tableted into a first module and combined with a second population of particles that is tableted into a second module, and wherein the second module is a an orally disintegrating tablet (ODT). 
     
     
         17 . The oral tablet according to any of the preceding claims, wherein the non-DC areas are evenly distributed in the tablet or at least one module of the tablet. 
     
     
         18 . The oral tablet according to any of the preceding claims, wherein a series of at least 10 of said tablets comprises said non-DC particles in an amount varying with a relative standard deviation (RSD) below 10%. 
     
     
         19 . The oral tablet according to any of the preceding claims, wherein the non-DC areas are homogenously distributed in the tablet or at least one module of the tablet. 
     
     
         20 . The oral tablet according to any of the preceding claims, wherein the tablet is a chewable tablet. 
     
     
         21 . The oral tablet according to any of the preceding claims, wherein at least 20% by weight of the non-DC sugar alcohol particles have a particle size above 500 μm. 
     
     
         22 . The oral tablet according to any of the preceding claims, wherein at least 30% by weight of the non-DC sugar alcohol particles have a particle size above 500 μm. 
     
     
         23 . The oral tablet according to any of the preceding claims, wherein at least 40% by weight of the non-DC sugar alcohol particles have a particle size above 500 μm. 
     
     
         24 . The oral tablet according to any of the preceding claims, wherein at least 10% by weight of said population of particles have a particle size below 250 μm, and wherein at least 30% by weight of said population of particles have a particle size above 500 μm. 
     
     
         25 . The oral tablet according to any of the preceding claims, wherein at least 10% by weight of the non-DC sugar alcohol particles have a particle size below 250 μm. 
     
     
         26 . The oral tablet according to any of the preceding claims, wherein at least 5% by weight of the non-DC sugar alcohol particles have a particle size below 250 μm. 
     
     
         27 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof. 
     
     
         28 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, isomalt, and combinations thereof. 
     
     
         29 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are selected from non-DC particles of erythritol, maltitol, xylitol, and combinations thereof. 
     
     
         30 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are non-DC erythritol particles. 
     
     
         31 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are non-DC xylitol particles. 
     
     
         32 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol particles are non-DC isomalt particles. 
     
     
         33 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said non-DC sugar alcohol particles in an amount of at least 10% by weight of the tablet. 
     
     
         34 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said non-DC sugar alcohol particles in an amount of at least 20% by weight of the tablet. 
     
     
         35 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said non-DC sugar alcohol particles in an amount of at least 30% by weight of the tablet. 
     
     
         36 . The oral tablet according to any of the preceding claims, wherein the first module comprises said non-DC sugar alcohol particles in an amount of at least 30% by weight of the first module. 
     
     
         37 . The oral tablet according to any of the preceding claims, wherein the first module comprises said non-DC sugar alcohol particles in an amount of at least 40% by weight of the first module. 
     
     
         38 . The oral tablet according to any of the preceding claims, wherein said DC sugar alcohol particles comprises sugar alcohols selected from DC particles of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, isomalt, and combinations thereof. 
     
     
         39 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said DC sugar alcohol particles in an amount of at least 10% by weight of the tablet. 
     
     
         40 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said DC sugar alcohol particles in an amount of at least 20% by weight of the tablet. 
     
     
         41 . The oral tablet according to any of the preceding claims, wherein the tablet comprises said DC sugar alcohol particles in an amount of at least 30% by weight of the tablet. 
     
     
         42 . The oral tablet according to any of the preceding claims, wherein the first module comprises said DC sugar alcohol particles in an amount of at least 30% by weight of the first module. 
     
     
         43 . The oral tablet according to any of the preceding claims, wherein the second module comprises DC sugar alcohol particles in an amount of at least 50% by weight of the second module. 
     
     
         44 . The oral tablet according to any of the preceding claims, wherein the second module comprises DC sugar alcohol particles in an amount of at least 70% by weight of the second module. 
     
     
         45 . The oral tablet according to any of the preceding claims, wherein the second module comprises DC sugar alcohol particles in an amount of at least 90% by weight of the second module. 
     
     
         46 . The oral tablet according to any of the preceding claims, wherein friability of the tablet is less than 3%, such as less than 2%, such as less than 1.5%, wherein friability is measured according to European Pharmacopoeia 9.1, test method 2.9.7. by using a pharmaceutical friability-tester PTF 10E from Pharma Test. 
     
     
         47 . The oral tablet according to any of the preceding claims, wherein the tablet comprises one or more binders other than binders forming part of the DC sugar alcohol particles in an amount of 0.1 to 6% by weight of the tablet. 
     
     
         48 . The oral tablet according to any of the preceding claims, wherein the resistance to crunching of the tablet is greater than 60N, such as greater than 70N, such as greater than 80N, such as greater than 90N, such as greater than 100 N, such as greater than 110, such as greater than 130N such as greater than 150N, wherein the resistance to crunching of the tablet is less than 300N, such as less than 250N, such as less than 200N, wherein the resistance to crunching is determined according to European Pharmacopoeia 9.1, test method 2.9.8. by using a pharmaceutical resistance to crunching tester model Pharma Test type PTB 311. 
     
     
         49 . The oral tablet according to any of the preceding claims, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles, which is between 0.2 and 1.2. 
     
     
         50 . The oral tablet according to any of the preceding claims, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles, which is between 0.3 and 1.0. 
     
     
         51 . The oral tablet according to any of the preceding claims, wherein the tablet has a weight ratio between said non-DC sugar alcohol particles and said DC sugar alcohol particles, which is between 0.3 and 0.7. 
     
     
         52 . The oral tablet according to any of the preceding claims, wherein the non-DC areas results in induced saliva generation. 
     
     
         53 . The oral tablet according to any of the preceding claims, wherein saliva generation upon mastication of the tablet is induced compared to a tablet without non-DC sugar alcohol particles. 
     
     
         54 . The oral tablet according to any of the preceding claims, wherein saliva generation upon mastication of the tablet is induced compared to a tablet where the discrete areas are based on DC sugar alcohol particles. 
     
     
         55 . The oral tablet according to any of the preceding claims, wherein the tablet generates more than 1.5 mL saliva within 30 seconds from onset of mastication. 
     
     
         56 . The oral tablet according to any of the preceding claims, wherein the tablet generates more than 1.5 mL saliva within a period from 30 to 90 seconds from onset of mastication. 
     
     
         57 . The oral tablet according to any of the preceding claims, wherein the tablet generates more than 1.5 mL saliva within a period from 90 to 180 seconds from onset of mastication. 
     
     
         58 . The oral tablet according to any of the preceding claims, wherein the tablet generates more than 1.5 mL saliva within a period from 180 to 300 seconds from onset of mastication. 
     
     
         59 . The oral tablet according to any of the preceding claims, further comprising at least one viscosity modifier. 
     
     
         60 . The oral tablet according to any of the preceding claims, wherein the at least one viscosity modifier is selected from the group consisting of sodium alginate, pectin, carrageenan, xanthan gum, acacia gum and mixtures thereof. 
     
     
         61 . The oral tablet according to any of the preceding claims, further comprising at least one viscolising agent that when hydrated forms a gel having positive surface electrical charge and at least one viscolising agent that when hydrated forms a gel having negative surface electrical charge. 
     
     
         62 . The oral tablet according to any of the preceding claims, wherein the tablet comprises an active ingredient. 
     
     
         63 . The oral tablet according to any of the preceding claims, wherein the tablet comprises a self-emulsifying system that when hydrated with saliva upon oral administration forms an emulsion. 
     
     
         64 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers and one or more oil carriers. 
     
     
         65 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers, one or more oil carriers and one or more solubilizers. 
     
     
         66 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers, one or more oil carriers, one or more solubilizers and one or more solvents. 
     
     
         67 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers and one or more solvents. 
     
     
         68 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers that have both emulsifying and solubilizing properties. 
     
     
         69 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers that act as both an emulsifier and a carrier. 
     
     
         70 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers that act as both an emulsifier, a carrier and a solubilizer. 
     
     
         71 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more fatty acids, one or more glycerols, one or more waxes, one or more flavonoids and one or more terpenes. 
     
     
         72 . The oral tablet according to any of the preceding claims, wherein the self-emulsifying system comprises one or more emulsifiers that have an HLB-value of more than 6, preferably of 8-18. 
     
     
         73 . The oral tablet according to any of the preceding claims, wherein the one or more emulsifiers are selected from the group consisting of PEG-35 castor oil, PEG-6 oleoyl glycerides, PEG-6 linoleoyl glycerides, PEG-8 caprylic/capric glyceride, sorbitan monolaurate, sorbitan monooleate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (60) sorbitan monostearate, polyoxyethylene (80) sorbitan monooleate, lauroylpoloxyl-32 glycerides, stearoyl polyoxyl-32 glycerides, polyoxyl-32 stearate, propylene glycol mono laurate, propylene glycol di laurate, and mixtures and combinations thereof. 
     
     
         74 . The oral tablet according to any of the preceding claims, wherein the one or more emulsifiers comprise PEG-35 castor oil. 
     
     
         75 . The oral tablet according to any of the preceding claims, wherein the oil carrier is selected from the group consisting of natural fatty acids; medium-chain triglycerides of caprylic (C8) and capric (C10) acids; propylene glycol esters of caprylic (C8) and capric (C10) acids; mono-, di- and triglycerides of mainly linoleic (C18:2) and oleic (C18:1) acids; fatty acid 18:1 cis-9; natural fatty acids; mono-, di- and triglycerides of oleic (C18:1) acid, and mixtures and combinations thereof. 
     
     
         76 . The oral tablet according to any of the preceding claims, wherein the one or more solvents are selected from the group consisting of polyglyceryl-3 dioleate, 1,2-propandiol, polyethylene glycol 300, polyethylene glycol 400, diethylene glycol monoethyl ether, and mixtures and combinations thereof. 
     
     
         77 . The oral tablet according to any of the preceding claims, wherein the one or more solubilizers are selected from the group consisting of lauroylpoloxyl-32 glycerides; stearoyl polyoxyl-32 glycerides; Polyoxyl-32 stearate; synthetic copolymer of ethylene oxide (80) and propylene oxide (27); polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer; alpha-, beta- or gamma cyclodextrins and derivatives thereof pea proteins (globulins, albumins, glutelins proteins); and
 mixtures and combinations thereof.   
     
     
         78 . The oral tablet according to any of the preceding claims, wherein the tablet comprises an active pharmaceutical ingredient. 
     
     
         79 . The oral tablet according to any of the preceding claims, wherein the tablet comprises an active pharmaceutical ingredient and a self-emulsifying system that when hydrated with saliva upon oral administration forms an emulsion. 
     
     
         80 . The oral tablet according to any of the preceding claims, wherein the tablet comprises nicotine and a self-emulsifying system that when hydrated with saliva upon oral administration forms an emulsion. 
     
     
         81 . The oral tablet according to any of the preceding claims, wherein the tablet comprises a lipophilic association between an active ingredient and a fatty acid, such as oleic acid. 
     
     
         82 . The oral tablet according to any of the preceding claims, wherein the tablet comprises particles comprising gum base, and wherein the tablet is designed to be masticated into a coherent residual containing water-insoluble components. 
     
     
         83 . The oral tablet according to any of the preceding claims, wherein the oral tablet contains particles comprising gum base, and wherein the gum base comprises at least 5% by weight of elastomer. 
     
     
         84 . The oral tablet according to any of the preceding claims, wherein the tablet is free of gum base. 
     
     
         85 . The oral tablet according to any of the preceding claims, wherein the oral tablet is essentially consisting of ingredients that are present in nature. 
     
     
         86 . The oral tablet according to any of the preceding claims, wherein the oral tablet comprises a natural high intensity sweetener, such as stevioside. 
     
     
         87 . The oral tablet according to any of the preceding claims, wherein the non-DC sugar alcohol is a non-DC sugar, such as a non-DC cane sugar. 
     
     
         88 . A disintegrating oral tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles, the tablet being designed to turn into liquid within 20 seconds of mastication. 
     
     
         89 . A disintegrating oral tablet suitable for active pharmaceutical ingredients comprising a population of particles, the population of particles comprising directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles, the tablet being designed to dissolve within 20 seconds of mastication. 
     
     
         90 . The disintegrating oral tablet according to any of  claim 88  or  89 , wherein the tablet is composed according to any of  claims 1 - 87 . 
     
     
         91 . A method of providing a burst of flavor, the method comprising the steps of:
 i) providing a disintegrating oral tablet comprising a population of particles and at least one flavor ingredient, the population of particles comprising directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles, and   ii) disintegrating the tablet by mastication and thereby generating a burst of flavor by means of a plurality of discrete non-DC areas in the tablet.   
     
     
         92 . The method according to  claim 91 , wherein the tablet is composed according to any of  claims 1 - 90 . 
     
     
         93 . A disintegrating oral product for providing a burst of flavor comprising a population of particles and at least one flavor ingredient, the population of particles comprising directly compressible (DC) and non-directly compressible (non-DC) sugar alcohol particles. 
     
     
         94 . The disintegrating oral product according to  claim 93 , wherein the product is a powder. 
     
     
         95 . The disintegrating oral product according to  claim 93 , wherein the product is a pouch. 
     
     
         96 . The disintegrating oral product according to  claims 93 - 95 , wherein the product is composed according to any of  claims 1 - 88 .