Coated particles with prolonged release and tablets containing same

• US 20050152976A1
• Filed: 04/23/2003
• Published: 07/14/2005
• Est. Priority Date: 04/23/2002
• Status: Active Grant

• Current Assignee: ETHYPHARM
• Original Assignee: ETHYPHARM
• Inventors: Marechal, Dominique, Chenevier, Phillippe
• Granted Patent: US 7,718,194 B2
• Time in Patent Office: Days
• US Class Current: 424/471
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50

Abstract

The invention concerns coated particles with prolonged release, a method for preparing same and multiparticulate tablets comprising said coated particles.

Claims

1. A multiparticulate tablet comprising:

a disintegrant and/or a swelling agent,

at least one diluent, and

a lubricant,

wherein the tablet is based on sustained-release coated particles comprising;

a core comprising an active principle and at least one binder, and

a coating film consisting of at least one cellulosic polymer, alone or as a mixture with a plasticizer, and

a protective coating based on at least one thermoplastic agent with a melting point of from about 25°

C. to about 100°

C. and which is applied to the coating film based on at least one cellulosic polymer, said thermoplastic agent being chosen from the group comprising partially hydrogenated oils, beeswax, carnauba wax, paraffin waxes, silicone waxes, fatty alcohols, C₁₂-C₁₈ fatty acids, solid semisynthetic glycerides, glyceryl monoesters, diesters or triesters, polyoxyethylene glycols and polyoxyethylenated glycosyl glycerides, and mixtures thereof.

2. The multiparticulate tablet of claim 1, wherein the protective coating of the sustained-release coated particles is chosen from excipients whose hydrophilic/lipophilic balance (HLB) is greater than 10.

3. The multiparticulate tablet of claim 1, further comprising a binder, a permeabilizer, sweeteners, flavorings and colorants, wherein the protective coating of the coated particles comprises an antistatic agent and a lubricant.

4. The multiparticulate tablet of claim 1, wherein the proportion of excipients mixture relative to the coated particles is from 0.4 to 10 and preferably from 1 to 5 parts by weight.

5. The multiparticulate tablet of claim 1, wherein the tablet disintegrates in a mouth on contact with saliva in less than 60 seconds and preferably in less than 40 seconds, forming a suspension that is easy to swallow.

6. The multiparticulate tablet of claim 5, wherein the tablet comprises at least one disintegrant, a diluent, a lubricant and optionally a swelling agent, a permeabilizer, sweeteners and flavorings.

7. The multiparticulate tablet of claim 5, wherein the diluent is chosen from soluble agents with binding properties, consisting of a polyol of less than 13 carbon atoms and being either in the form of a directly compressible product with a mean particle diameter of from 100 to 500 μ

m, or in the form of a powder with a mean particle diameter of less than 100 μ

m, this polyol preferably being chosen from the group comprising mannitol, xylitol, sorbitol and maltitol, used in the form of a directly compressible product, whereas, in the case where there are at least two soluble diluents with binding properties, one is present in the directly compressible form and the other in the form of a powder, the polyol possibly being the same, the proportions of directly compressible polyol and of polyol powder being from 99/1 to 20/80 and preferably from 80/20 to 20/80.

8. The multiparticulate tablet of claim 1, wherein the coated particles comprise at least one active principle chosen from those of the group comprising gastrointestinal sedatives, antacids, analgesics, antiinflammatories, coronary vasodilators, peripheral and cerebral vasodilators, antiinfectives, antibiotics, antiviral agents, antiparasitic agents, anticancer agents, anxiolytics, neuroleptics, central nervous system stimulants, antidepressants, antihistamines, antidiarrheal agents, laxatives, dietary supplements, immunodepressants, hypocholesterolemiants, hormones, enzymes, antispasmodics, antianginal agents, medicinal products that affect the heart rate, medicinal products used in the treatment of arterial hypertension, antimigraine agents, medicinal products that affect blood clotting, antiepileptics, muscle relaxants, medicinal products used in the treatment of diabetes, medicinal products used in the treatment of thyroid dysfunctions, diuretics, anorexigenic agents, antiasthmatics, expectorants, antitussive agents, mucoregulators, decongestants, hypnotics, antinausea agents, hematopoietic agents, uricosuric agents, plant extracts and contrast agents.

9. The multiparticulate tablet of claim 1, wherein the binder included in the constitution of the coated particles is chosen from the group comprising cellulosic polymers, acrylic polymers, povidones, copovidones, polyvinyl alcohols, alginic acid, sodium alginate, starch, pregelatinized starch, sugars and derivatives thereof, guar gum and polyethylene glycols, and mixtures thereof.

10. The multiparticulate tablet of claim 1, wherein:

the core of the coated particles comprises a diluent and an antistatic agent,

the cellulosic polymer borne by the coated particles is ethylcellulose,

the coating film of the coated particles comprises a pore-forming agent, a plasticizer, a surfactant, an antistatic agent and a lubricant, and

a polymer layer is applied between the core and the functional polymer film borne by the coated particles.

11. The multiparticulate tablet of claim 1, wherein the diameter of the coated particles is from 150 to 700 μ

m, given that the diameter of at least 50% and preferably of at least 70% of the particles is between 150 and 500 μ

m, and that the diameter of less than 15% of the particles is less than 150 μ

m.

12. A method for preparing coated particles borne by the multiparticulate tablet of claim 1, the method comprising:

(a) preparing by wet granulation or mounting on neutral supports, of a core comprising the active principle,

(b) coating of the cores thus obtained by spraying a coating composition consisting of at least one cellulosic polymer,

(c) coating of the coated particles thus obtained by spraying with a protective coating composition consisting of an excipient of thermoplastic type, dissolved in an aqueous solvent devoid of organic solvent,

(d) drying.

15. The multiparticulate tablet of claim 1, further comprising a binder, a permeabilizer, sweeteners, flavorings and colorants and in that the protective coating of the coated particles comprises an antistatic agent and a lubricant.

21. The multiparticulate tablet of claim 15, wherein the binder included in the constitution of the coated particles is chosen from the group comprising cellulosic polymers, acrylic polymers, povidones, copovidones, polyvinyl alcohols, alginic acid, sodium alginate, starch, pregelatinized starch, sugars and derivatives thereof, guar gum and polyethylene glycols, and mixtures thereof.

13. A multiparticulate tablet comprising

a disintegrant and/or a swelling agent,

at least one diluent,

a lubricant, and

an antistatic agent, a permeabilizer, sweeteners, flavorings and colorants,

wherein the tablet is based on sustained-release coated particles comprising

a core comprising an active principle and at least one binder, and

a coating film consisting of at least one cellulosic polymer, alone or as a mixture with a plasticizer, and

a protective coating based on at least one thermoplastic agent with a melting point of from about 25°

C. to about 100°

C. and which is applied to the coating film based on at least one cellulosic polymer, said thermoplastic agent being chosen from the group comprising partially hydrogenated oils, beeswax, carnauba wax, paraffin waxes, silicone waxes, fatty alcohols, C₁₂-C₁₈ fatty acids, solid semisynthetic glycerides, glyceryl monoesters, diesters or triesters, polyoxyethylene glycols and polyoxyethylenated glycosyl glycerides, and mixtures thereof.

14. The multiparticulate tablet of claim 13, wherein the protective coating of the sustained-release coated particles is chosen from excipients whose hydrophilic/lipophilic balance (HLB) is greater than 10.

16. The multiparticulate tablet of claim 13, wherein the proportion of excipients mixture relative to the coated particles is from 0.4 to 10 and preferably from 1 to 5 parts by weight.

17. The multiparticulate tablet of claim 13, wherein the tablet disintegrates in a mouth on contact with saliva in less than 60 seconds and preferably in less than 40 seconds, forming a suspension that is easy to swallow.

18. The multiparticulate tablet of claim 16, wherein the tablet comprises at least one disintegrant, a diluent, a lubricant and optionally a swelling agent, a permeabilizer, sweeteners and flavorings.

19. The multiparticulate tablet of claim 18, wherein the diluent is selected from soluble agents with binding properties, consisting of a polyol of less than 13 carbon atoms and being either in the form of a directly compressible product with a mean particle diameter of from 100 to 500 μ

m, or in the form of a powder with a mean particle diameter of less than 100 μ

m, this polyol preferably being chosen from the group comprising mannitol, xylitol, sorbitol and maltitol, used in the form of a directly compressible product, whereas, in the case where there are at least two soluble diluents with binding properties, one is present in the directly compressible form and the other in the form of a powder, the polyol possibly being the same, the proportions of directly compressible polyol and of polyol powder being from 99/1 to 20/80 and preferably from 80/20 to 20/80.

20. The multiparticulate tablet of claim 13, wherein the coated particles comprise at least one active principle selected from those of the group consisting of gastrointestinal sedatives, antacids, analgesics, antiinflammatories, coronary vasodilators, peripheral and cerebral vasodilators, antiinfectives, antibiotics, antiviral agents, antiparasitic agents, anticancer agents, anxiolytics, neuroleptics, central nervous system stimulants, antidepressants, antihistamines, antidiarrheal agents, laxatives, dietary supplements, immunodepressants, hypocholesterolemiants, hormones, enzymes, antispasmodics, antianginal agents, medicinal products that affect the heart rate, medicinal products used in the treatment of arterial hypertension, antimigraine agents, medicinal products that affect blood clotting, antiepileptics, muscle relaxants, medicinal products used in the treatment of diabetes, medicinal products used in the treatment of thyroid dysfunctions, diuretics, anorexigenic agents, antiasthmatics, expectorants, antitussive agents, muco-regulators, decongestants, hypnotics, antinausea agents, hematopoietic agents, uricosuric agents, plant extracts and contrast agents.

22. The multiparticulate tablet of claim 13, wherein:

the core of the coated particles comprises a diluent and an antistatic agent,

the cellulosic polymer borne by the coated particles is ethylcellulose,

the coating film of the coated particles comprises a pore-forming agent, a plasticizer, a surfactant, an antistatic agent and a lubricant, and

a polymer layer is applied between the core and the functional polymer film borne by the coated particles.

23. The multiparticulate tablet of claim 13, wherein the diameter of the coated particles is from 150 to 700 μ

m, given that the diameter of at least 50% and preferably of at least 70% of the particles is between 150 and 500 μ

m, and that the diameter of less than 15% of the particles is less than 150 μ

m.

24. A method for preparing coated particles borne by the multiparticulate tablet of claim 13, the method comprising:

(a) preparing by wet granulation or mounting on neutral supports, of a core comprising the active principle,

(b) coating of the cores thus obtained by spraying the coating composition consisting of at least one cellulosic polymer,

(c) coating of the coated particles thus obtained by spraying with a protective coating composition consisting of an excipient of thermoplastic type, dissolved in an aqueous solvent devoid of organic solvent,

(d) drying.