Modified release formulations containing drug-ion exchange resin complexes
An aqueous liquid suspension containing a coated drug-ion exchange resin complex comprising a core composed of an amphetamine complexed with a pharmaceutically acceptable ion-exchange resin and an uncoated amphetamine-ion exchange resin complex is provided. The coated amphetamine-ion exchange resin complex is in admixture with a polymer to form a matrix. Methods of making the coated complex and the liquid suspension are described.
1. A solid pharmaceutical composition suitable for oral ingestion comprising modified release, barrier coated particulates which comprise:
(i) a particulate dextromethorphan-cation exchange resin complex-matrix comprising dextromethorphan bound to a pharmaceutically acceptable water insoluble cation exchange resin, wherein the dextromethorphan-cation exchange resin complex is in a matrix with a water insoluble polymer or copolymer or a hydrophilic polymer, and
(ii) about 25% w/w to about 50% w/w of a water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating based on the weight of the dextromethorphan-cation exchange resin complex-matrix of (i) prior to coating, wherein the barrier coating has an elongation factor of about 125% to about 400%, provides a modified release to the dextromethorphan in the barrier coated particulate dextromethorphan-cation exchange resin complex-matrix defined in (i), and comprises (a) about 70% w/w to about 90% w/w of a water-insoluble polymer based on the weight of the barrier coating layer and (b) about 2.5% w/w to about 20% w/w of a plasticizer based on the weight of the barrier coating layer, whereby the water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating is over the particulate dextromethorphan-cation exchange resin complex-matrix and provides a modified release profile to said pharmaceutically acceptable drug in said particulate dextromethorphan-cation exchange resin complex-matrix.
2. The composition according to claim 1 which is a tablet.
3. The composition according to claim 1 , wherein the about 70% w/w to about 90% w/w water-insoluble polymer is polyvinylacetate.
4. The solid pharmaceutical composition according to claim 1 , wherein and the barrier coating further comprises a stabilizer.
5. The solid pharmaceutical composition according to claim 1 , wherein the stabilizer comprises polyvinylpyrrolidone.
6. The solid pharmaceutical composition according to claim 1 , wherein the plasticizer is selected from dibutyl sebacate, propylene glycol, polyethylene glycol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, or triacetin, or mixtures thereof.
7. The solid pharmaceutical composition according to claim 1 , wherein the matrix comprises the particulate dextromethorphan-cation exchange resin complex and about 3% to about 30% by weight of the hydrophilic polymer, based on the weight of the particulate dextromethorphan-ion exchange resin complex-matrix prior to coating.
8. The solid pharmaceutical composition according to claim 1 , wherein the matrix comprises the particulate dextromethorphan-cation exchange resin complex and about 5% to about 20% by weight of the hydrophilic polymer which comprises polyvinylpyrrolidone, based on the weight of the particulate dextromethorphan-cation exchange resin complex-matrix prior to coating.
9. The solid pharmaceutical composition according to claim 1 which further comprises a second active component.
10. The solid pharmaceutical composition according to claim 9 , wherein the second active component is not in a drug-ion exchange resin complex.
11. The solid pharmaceutical composition according to claim 9 , wherein the second active component is in a drug-ion exchange resin complex.
12. The solid pharmaceutical composition according to claim 9 , wherein the further active ingredient is pseudoephedrine.
13. The solid pharmaceutical composition according to claim 1 , which further comprises a dextromethorphan-cation exchange resin complex which is uncoated with a modified release barrier coating.
14. A method for oral administration of a modified release drug to a subject in need thereof, said method comprising administering to said subject a product according to claim 1 .
15. A pharmaceutical tablet suitable for oral ingestion comprising:
(A) a particulate dextromethorphan-ion exchange resin complex-optional matrix comprising:
(i) dextromethorphan bound to a pharmaceutically acceptable water insoluble cation exchange resin to form said particulate dextromethorphan-cation exchange resin complex-optional matrix, said particulate dextromethorphan-cation exchange resin complex optionally being in a matrix with a water insoluble polymer or copolymer or a hydrophilic polymer, which polymer or copolymer is present in an amount of about 3% to about 30% by weight, based on the weight of said particulate dextromethorphan-cation exchange resin complex-optional matrix, and
(ii) a water permeable, water insoluble, non-ionic polymeric diffusion modified release barrier coating over said particulate dextromethorphan-ion exchange resin complex-optional matrix defined in (i), the water permeable, water insoluble, non-ionic polymeric, modified release, diffusion barrier coating applied as an aqueous dispersion, wherein the barrier coating comprises:
(a) about 75% w/w to about 90% w/w polyvinylacetate polymer;
(b) a stabilizer comprising polyvinylpyrrolidone, and
(c) about 2.5% w/w to about 20% w/w of plasticizer effective to enhance the tensile strength of the water permeable, water insoluble, non-ionic polymeric, modified release diffusion barrier coating, whereby the water permeable, water insoluble, non-ionic polymeric, modified release, diffusion barrier coating is over the particulate dextromethorphan-ion exchange resin complex-optional matrix and provides a modified release profile to said pharmaceutically acceptable dextromethorphan in the particulate dextromethorphan-cation exchange resin complex-optional matrix; and
(B) one or more pharmaceutically acceptable excipient.
16. The tablet according to claim 12 , wherein said ion exchange resin is a sulfonated copolymer comprising styrene and a divinylbenzene.
17. The tablet according to claim 12 , wherein the barrier coating layer comprises about 5% to about 10% by weight plasticizer.
18. The tablet according to claim 17 , wherein the plasticizer comprises triacetin.
19. The tablet according to claim 12 , wherein the particulate dextromethorphan-ion exchange resin complex is of a size capable of passing through a number 40 mesh screen.
20. The tablet according to claim 12 , wherein the barrier coating is cured.
21. The tablet according to claim 12 , wherein the matrix is present and comprises the particulate dextromethorphan-cation exchange resin complex and about 5% to about 20% by weight of the hydrophilic polymer which comprises polyvinylpyrrolidone, based on the weight of the particulate dextromethorphan-cation exchange resin complex-matrix prior to coating.
22. The tablet according to claim 12 which further comprises a second active component.
23. The tablet according to claim 22 , wherein the second active component is not in a drug-ion exchange resin complex.
24. The tablet according to claim 22 , wherein the second active component is in a drug-ion exchange resin complex.
25. The tablet according to claim 22 wherein the second active ingredient is pseudoephedrine.
26. The tablet according to claim 12 , which further comprises a dextromethorphan-cation exchange resin complex which is uncoated with a modified release barrier coating.
27. A method for oral administration of a modified release drug to a subject in need thereof, said method comprising administering to said subject a product according to claim 12 .