Claims for Patent: 6,730,325

Summary for Patent: 6,730,325

Title:	Multiparticulate modified release composition
Abstract:	The invention relates to a multiparticulate modified release composition that in operation delivers an active ingredient in a pulsed or bimodal manner. The multiparticulate modified release composition comprises an immediate release component and a modified release component; the immediate release component comprising a first population of active ingredient containing particles and the modified release component comprising a second population of active ingredient containing particles coated with a controlled release coating; wherein the combination of the immediate release and modified release components in operation deliver the active ingredient in a pulsed or a bimodal manner. The invention also relates to a solid oral dosage form containing such a multiparticulate modified release composition. The plasma profile achieved by the multiparticulate modified release composition is advantageous in reducing patient tolerance to the active ingredient and in increasing patient compliance by reducing dosage frequency.
Inventor(s):	Devane; John G. (Athlone, IE), Stark; Paul (Athlone, IE), Fanning; Niall M. M. (Athlone, IE)
Assignee:	Elan Corporation, plc (Dublin, IE)
Application Number:	09/850,425
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,730,325
Patent Claims:	1. A multiparticulate modified release composition comprising a first population of acitve ingredient-containing particles and at least one subsequent population of active ingredient-containing particles, wherein the acitive ingredient contained in the first population is a drug compound that acts on the central nervous system, and the subsequent population of active ingredient-containing particles further comprises a modified release coating or, alternatively or additionally, a modified release matrix material, such that the composition following oral delivery to a subject delivers the active ingredients in the first and subsequent populations in a pulsatile manner. 2. The composition according to claim 1, comprising a first population and one subsequent population. 3. The composition according to claim 2, wherein the first population comprises immediate-release particles and the subsequent population comprises modified-release particles. 4. The composition according to claim 3, wherein the modified release particles have a modified-release coating. 5. The composition according to claim 2, wherein the modified release particles comprise a modified-release matrix material. 6. The composition according to claim 1, wherein the first population contains a cerebral stimulant. 7. The composition according to claim 1, wherein the first population contains methylphenidate or a pharmaceutically acceptable salt thereof, an enantiomer or a mixture thereof racemic or otherwise, or a mixture thereof. 8. The composition according to claim 1, wherein the composition contains at least one additional active ingredient. 9. The composition according to claim 1, wherein at least one of the first and subsequent populations further comprises an enhancer. 10. The composition according to claim 1, wherein the amount of active ingredient contained in each of the first and subsequent populations is from about 0.1 mg to about 1 g. 11. The composition according to claim 1, wherein the first and subsequent populations have different in vitro dissolution profiles. 12. The composition according to claim 1, wherein the particles of the first population comprise immediate-release particles and the particles of the subsequent population comprise modified-release particles. 13. The composition according to claim 12, which in operation releases substantially all of the active ingredient from the first population prior to release of the active ingredient from the subsequent population. 14. The composition according to claim 1, wherein the in vivo release in the subject of the active ingredients from the first and subsequent populations mimics the in vivo release of the same active ingredients administered in the form of two or more doses of immediate-release forms of the active ingredients. 15. The composition according to claim 13, wherein the mean in vitro dissolution profile in an aqueous medium is such that substantially all of the active ingredient of the first population is released within about two hours. 16. A dosage form comprising a composition according to claim 1. 17. A dosage form comprising a composition according to claim 6. 18. A dosage form comprising a composition according to claim 2. 19. The dosage form according to claim 16 comprising a blend of the particles of each of the first and subsequent populations contained in a hard gelatin or soft gelatin capsule. 20. The dosage form according to claim 19, wherein the particles of each of the populations are in the form of mini-tablets and the capsule contains a mixture of the mini-tablets. 21. The dosage form according to claim 16 in the form of a multilayer tablet comprising a first layer of compressed active ingredient-containing particles of the first population and another layer of compressed active ingredient-containing particles of the subsequent population. 22. The dosage form according to claim 16, wherein the first and subsequent populations of active ingredient-containing particles are provided in a rapidly dissolving dosage form. 23. The dosage form according to claim 22, comprising a fsat-melt tablet. 24. A method for the treatment of attention deficit disorder comprising administering a therapeutically effective amount of a composition according to claim 7. 25. The composition according to claim 2, wherein the modified-release particles comprise a pH-dependent polymer coating which is effective in releasing a pulse of the active ingredient following a time delay. 26. The composition according to claim 25, wherein the polymer coating comprises methacrylate copolymers. 27. The composition according to claim 25, wherein the polymer coating comprises a mixture of methacrylate and ammonio methacrylate copolymers in a ratio sufficient to achieve a pulse of the active ingredient following a time delay. 28. The composition according to claim 27, wherein the ratio of methacrylate to ammonio methacrylate copolymers is 1:1.