Multiparticulate tablet disintegrating in less than 40 seconds in the mouth

• US 6,106,861 A
• Filed: 12/05/1997
• Issued: 08/22/2000
• Est. Priority Date: 07/21/1997
• Status: Expired due to Term

• Current Assignee: ETHYPHARM
• Original Assignee: Laboratories Perouse SAS (Laboratories Perouse)
• Inventors: Nouri, Noureddine, Demichelis, Alain Gilles, Chauveau, Charles, Gendrot, Edouard
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Seidleck, Brian K.
• Application Number:
  US08/985,793
• Time in Patent Office: 991 Days
• Field of Search: 424/464, 424/465, 424/470, 424/474, 424/479, 424/489, 424/493, 424/494, 424/497, 424/469, 514/960
• US Class Current: 424/465
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50

Abstract

The invention relates to a rapidly disintegratable multiparticulate tablet which disintegrates in the mouth in less than 40 seconds and which comprises an excipient and an active ingredient in the form of microcrystals coated with a coating agent. The excipient comprises, with respect to the mass of the tablet, from 3 to 15% by weight of at least one disintegration agent and from 40 to 90% by weight of at least one soluble diluent agent with binding properties consisting of a polyol having less than 13 carbon atoms, said polyol being either in the directly compressible form which is composed of particles whose average diameter is from 100 to 500 micrometers or in the powder form which is composed of particles whose average diameter is less than 100 micrometers, said polyol being selected from the group consisting of mannitol, xylitol, sorbitol and maltitol, with the proviso that, when only one soluble diluent agent with binding properties is used, it is a polyol in the directly compressible form except sorbitol and, when at least two soluble diluent agents with binding properties are used, one is consisting of a polyol in the directly compressible form and the other is consisting of the same or another polyol in powder form, the proportion of directly compressible polyol to powder polyol being from 99/1 to 50/50.

Claims

1. A multiparticulate tablet disintegrating in the mouth in less than 40 seconds and comprising an excipient and an active ingredient in the form of microcrystals comprising a taste-making coating wherein

the excipient comprises, with respect to the mass of the tablet, from 3 to 15% by weight of at least one disintegration agent selected from the group consisting of cross-linked polyvinylpyrrolidone and cross-linked carboxymethylcellulose and from 40 to 90% by weight of at least one soluble diluent agent with binding properties consisting of a polyol having less than 13 carbon atoms, said polyol being either in the directly compressible form which is composed of particles whose average diameter is from 100 to 500 micrometers or in the powder form which is composed of particles whose average diameter is less than 100 micrometers, said polyol being selected from the group consisting of mannitol, xylitol, sorbitol and maltitol, with the proviso that, when only one soluble diluent agent with binding properties is used, it is a polyol in the directly compressible form except sorbitol and, when at least two soluble diluent agents with binding properties are used, these are consisting of the same polyol, one part of which is in the directly compressible form while the other part is in powder form, the proportion of directly compressible polyol to powder polyol being from 99/1 to 50/50 and

the coating of the microcrystals of active ingredient comprises at least one coating agent selected as a function of the physico-chemical characteristics of the active ingredient selected from the group consisting of polymethacrylates and cellulose polymers and combinations thereof with each other.

2. A multiparticulate tablet according to claim 1, wherein the proportion of disintegrating agent and of soluble diluent agent with binding properties is respectively from 5 to 10% and from 50 to 70% by weight.

3. A multiparticulate tablet according to one of claim 1 or 2, wherein the maximum proportion of sorbitol is 30% by weight.

4. A multiparticulate tablet according to claim 1, wherein the proportion of directly compressible polyol to powder polyol is from 80/20 to 50/50.

5. A multiparticulate tablet according to claim 1, wherein the coating agent is selected from the group consisting of hydroxypropyl-methyl cellulose, hydroxypropyl cellulose and cellulose acetophthalates.

6. A multiparticulate tablet according to claim 1, wherein the coating agent is combined with at least one of the products of the group consisting of plasticizers, soluble agents and polyols.

7. A multiparticulate tablet according to claim 1, wherein the bioavailability of the active ingredient is at least equivalent to that of the active ingredient of the same tablet wherein the said active ingredient is not coated, allowing thus its immediate release.

8. A multiparticulate tablet according to claim 7, wherein the quantity of active ingredient which is dissolved from the coated microcrystals, after disintegration of the tablet, in 5 to 20 minutes when placed in an acid medium having a pH lower than 5, is equal to at least 80% of the quantity of active ingredient which is dissolved in the same time after disintegration from a tablet which is identical except the fact that the microcrystals are not coated.

9. A multiparticulate tablet according to claim 7, wherein the quantity of active ingredient which is dissolved from the coated microcrystals, after disintegration of the tablet, in 5 to 20 minutes when placed in an acid medium having a pH lower than 5, is equal to at least 100% of the quantity of active ingredient which is dissolved in the same time after disintegration from a tablet which is identical except the fact that the microcrystals are not coated.

10. A multiparticulate tablet according to one of claims 7 to 9, wherein the active ingredient does not dissolve significantly after remaining for a period of less than 5 minutes in a medium the pH conditions of which is 7.0±

0.5, thus providing satisfactory masking of the taste.

11. A multiparticulate tablet according to claim 1, wherein the active ingredient is selected from the group consisting of analgesics, antipyretics, antidiarrheals, antispasmodics, digestive motoricity regulators and anti-inflammatories.

12. A multiparticulate tablet according to claim 1, wherein the active ingredient is selected from the group consisting of paracetamol, ibuprofen, aspirin, ketoprofen and loperamide.