Controlled release budesonide minitablets

1. A controlled release minitablet comprising an extended release core and a pH dependent delayed release coating thereon, wherein:

the extended release core comprises a homogeneous mixture of budesonide, a carrier, at least one extended release polymer, a plasticizer, and an acid;

the pH dependent delayed release coating comprises an anionic carboxylic polymer that is soluble in water at a pH of about 4 to about 8 and insoluble at a pH of about 1 to about 3; and

the pH dependent delayed release coating is in direct contact with the homogeneous mixture of the extended release core.

2. The controlled release minitablet of claim 1 wherein the budesonide is embedded in the extended release polymer.

3. The controlled release minitablet of claim 1 wherein the at least one extended release polymer is selected from the group consisting of water insoluble polymers, water soluble polymers, and mixtures thereof.

4. The controlled release minitablet of claim 1 wherein the at least one extended release polymer comprises a member selected from the group consisting of ethyl cellulose, cellulose acetate, cellulose acetate butyrate, ethylene vinylacetate copolymer, polyvidone acetate, polyvinyl acetate, ethyl acrylate/methyl methacrylate copolymer, ammonia methacrylate copolymer, methylcellulose, hydroxypropyl cellulose, and combinations thereof;

wherein the acid is selected from the group consisting of citric acid, tartaric acid, acetic acid, ascorbic acid, malic acid, and combinations thereof; and

wherein the carrier comprises sugar, starch, microcrystalline celluloses, or a combination of these materials.

5. The controlled release minitablet of claim 1 wherein the extended release polymer and budesonide are present in the minitablet at a ratio by weight of about 0.1:1 to about 20:1, respectively.

6. The controlled release minitablet of claim 1 wherein the acid and budesonide are present in the minitablet at a ratio by weight of about 0.1:1 to about 10:1, respectively.

7. The controlled release minitablet of claim 1 wherein the weight of the carrier is from about 25% to about 95% of the total weight of the controlled release minitablet.

8. The controlled release minitablet of claim 1 wherein the weight of the pH dependent delayed release coating is from about 1 to about 50% of the total weight of the controlled release minitablet.

9. The controlled release minitablet of claim 1 wherein the pH dependent delayed release coating comprises at least one member selected from the group consisting of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethylcellulose phthalate, polyvinyl acetate phthalate, acrylic acid polymers, and combinations thereof.

10. The controlled release minitablet of claim 1 wherein the minitablet has a diameter of from about 1 mm to about 7.8 mm.

11. The controlled release minitablet of claim 1 wherein the plasticizer is selected from the group consisting of acetyltributyl citrate, acetyltriethyl citrate, dibutyl sebacate, tri-n-butyl citrate, and triethyl citrate.

12. The controlled release minitablet of claim 1 wherein the plasticizer is acetyltributyl citrate.

13. The controlled release minitablet of claim 12 wherein the extended release polymer is ethylcellulose polymer.

14. A controlled release minitablet comprising an extended release core and a pH dependent delayed release coating thereon, wherein:

the extended release core comprises a homogeneous mixture of budesonide, a carrier, at least one extended release polymer, a plasticizer, and an acid

the pH dependent delayed release coating comprises at least one anionic carboxylic polymer chosen from cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethylcellulose phthalate, polyvinyl acetate phthalate, acrylic acid polymers, and combinations thereof; and

the pH dependent delayed release coating is in direct contact with the homogeneous mixture of the extended release core.

15. The controlled release minitablet of claim 14 wherein the plasticizer is selected from the group consisting of acetyltributyl citrate, acetyltriethyl citrate, dibutyl sebacate, tri-n-butyl citrate, and triethyl citrate.

16. The controlled release minitablet of claim 14 wherein the plasticizer is acetyltributyl citrate.

17. The controlled release minitablet of claim 16 wherein the extended release polymer is ethylcellulose polymer.

18. A method of making controlled release minitablets comprising:

feeding a carrier into a fluidized bed reactor;

spraying a suspension comprising a homogeneous mixture of budesonide, acid, a plasticizer, and an extended release polymer onto the carrier to produce a granulated mixture;

milling the granulated mixture;

compressing the granulated mixture into extended release cores; and

coating the extended release cores with a pH dependent delayed release coating to produce a controlled release minitablet, wherein the pH dependent delayed release coating comprises an anionic carboxylic polymer that is soluble in water at a pH of about 4 to about 8 and insoluble at a pH of about 1 to about 3, and wherein the pH dependent delayed release coating is in direct contact with the homogeneous mixture of the extended release cores.

19. The method of claim 18 further comprising blending the milled granulated mixture with at least one lubricant, at least one disintegrant, or combinations thereof prior to the compression step.

20. The method of claim 18 wherein the plasticizer is selected from the group consisting of acetyltributyl citrate, acetyltriethyl citrate, dibutyl sebacate, tri-n-butyl citrate, and triethyl citrate.

21. The method of claim 18 wherein the plasticizer is acetyltributyl citrate.

22. The method of claim 21 wherein the extended release polymer is ethylcellulose polymer.