STABLE PANCREATIC ENZYME COMPOSITIONS

• US 20080274174A1
• Filed: 02/20/2008
• Published: 11/06/2008
• Est. Priority Date: 02/20/2007
• Status: Active Grant

• Current Assignee: Societe des Produits Nestle SA (Nestle SA)
• Original Assignee: Aptalis Pharma US Incorporated (Abbvie Incorporated)
• Inventors: Mapelli, Luigi, Marconi, Marco, Ortenzi, Giovanni
• Granted Patent: US 8,221,747 B2
• Time in Patent Office: Days
• US Class Current: 424/452
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2813 Inorganic compounds
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/501 Inorganic compounds
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Y 301/01003 Triacylglycerol lipase (3.1.1.3)

Abstract

Compositions of the present invention, comprising at least one digestive enzyme (e.g., pancrelipase) are useful for treating or preventing disorders associated with digestive enzyme deficiencies. The compositions of the present invention can comprise a plurality of coated particles, each of which is comprised of a core coated with an enteric coating comprising at least one enteric polymer and 4-10% of at least one alkalinizing agent, or have moisture contents of about 3% or less, water activities of about 0.6 or less, or exhibit a loss of activity of no more than about 15% after six months of accelerated stability testing.

Claims

1. A pancrelipase composition comprising a plurality of coated particles, each of which is comprised of a core coated with an enteric coating;

wherein the core comprises pancrelipase, at least one disintegrant, and at least one polymeric binder, and the enteric coating comprises at least one enteric polymer and 4-10 wt. % of at least one alkalinizing agent, based on the total weight of the composition.

2. The composition of claim 1, wherein said composition has a moisture content of about 3% or less.

3. The composition of claim 1, wherein said composition has a moisture content of about 2% or less.

4. The composition of claim 1, wherein said composition has a water activity of about 0.6 or less.

5. The composition of claim 1, wherein the at least one disintegrant is croscarmellose sodium, the at least one polymeric binder is microcrystalline cellulose, the enteric polymer is hydroxypropylmethylcellulose phthalate, and the alkalinizing agent is talc.

6. The composition of claim 1, wherein the core further comprises one or more exipients selected from the group consisting of plasticizers, glidants, lubricants, and combinations thereof, and the coating further comprises at least one plasticizer.

7. The composition of claim 6, wherein the core further comprises hydrogenated castor oil, colloidal silicon dioxide, and magnesium stearate;

and the coating further comprises triethyl citrate.

8. The composition of claim 1, wherein the core comprises 60-90 wt. % of pancrelipase, 1-4 wt. % of at least one disintegrant, and 2-6 wt. % of at least one polymeric binder, based on the total weight of the composition.

9. The composition of claim 8, wherein the disintegrant is croscarmellose sodium, and the polymeric binder is microcrystalline cellulose.

10. The composition of claim 1, wherein the coating comprises 10-20 wt. % of hydroxypropylmethylcellulose phthalate, based on the total weight of the composition.

11. The composition of claim 1, wherein the core comprises:

60-90 wt. % of pancrelipase;

1-4 wt. % of at least one disintegrant;

0.5-1.0 wt. % of at least one plasticizer;

0.2-0.6 wt. % of at least one glidant;

2-6 wt. % of at least one polymeric binder;

0.2-0.6 wt. % of at least one lubricant;

the coating comprises;

10-20 wt. % of at least one enteric polymer;

4-10 wt. % of at least one alkalinizing agent; and

1-2 wt. % of at least one plasticizer, based on the total weight of the composition.

12. The composition of claim 11, wherein the at least one disintegrant is croscarmellose sodium, the at least one plasticizer of the core is hydrogenated castor oil, the at least one polymeric binder is microcrystalline cellulose, the at least one lubricant is magnesium stearate, the at least one enteric polymer is hydroxypropylmethylcellulose phthalate, the at least one alkalinizing agent is talc, and the at least one plasticizer of the coating is triethyl citrate.

13. A capsule filled with the plurality of coated particles of claim 1, wherein the capsule has a moisture content of less than about 4%.

14. A capsule filled with the plurality of coated particles of claim 1, wherein the capsule has a moisture content of less than about 2%.

15. A capsule filled with the plurality of coated particles of claim 11, wherein the capsule has a moisture content of less than about 4%.

16. A capsule filled with the plurality of coated particles of claim 11, wherein the capsule has a moisture content of less than about 2%.

17. A capsule comprised of hydroxypropylmethylcellulose filled with the plurality of coated particles of claim 1.

18. A capsule comprised of hydroxypropylmethylcellulose filled with the plurality of coated particles of claim 11.