Details for Patent: 7,863,316

Title:	Extended release formulation of Levetiracetam
Abstract:	The present invention relates to extended release pharmaceutical compositions of Levetiracetam and processes for preparing the same. The extended release tablet of Levetiracetam is with a core comprising of Levetiracetam and water dispersible rate controlling polymer, and the tablet core is optionally functional coated comprising a combination of water non-dispersible and/or water dispersible polymer. It provides extended therapeutically effective plasma levels over a twenty four hour period with diminished incidences of neuropsychiatric adverse events by eliminating the troughs and peaks of drug concentration in a patient's blood plasma. The composition also exhibits no food effect.
Inventor(s):	Kshirsagar; Rajesh (Gujarat, IN), Rao; Ashwin (Gujarat, IN), Malaviya; Nilesh (Gujarat, IN), Jinturkar; Kaustubh (Gujarat, IN)
Assignee:	UCB Pharma S.A. (Brussels, BE)
Filing Date:	Oct 20, 2006
Application Number:	11/583,888
Claims:	1. An extended release tablet of levetiracetam comprising a) from about 30% to about 85% w/w of the tablet of levetiracetam and about 1% to about 50% w/w of the tablet of a water dispersible rate controlling polymer selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, sodium alginate, carbomer, sodium carboxymethyl cellulose, xanthan gum, guar gum, locust bean gum, poly vinyl acetate, polyvinyl alcohol and hydroxypropyl methylcellulose b) a functional coating comprising: i) from about 40% to about 90% w/w of the functional coating of a hydrophobic rate controlling polymer selected from the group consisting of cellulose ethers, cellulose acetate, polyvinyl acetate, neutral polymers of methacrylic acid esters, polyvinyl alcohol-maleic anhydride copolymers and mixtures thereof; ii) from about 10% to about 60% w/w of the functional coating of a channeling agent selected from the group consisting of copolyvidone, polyvinyl pyrrolidone, polyethylene glycols, hydroxyethyl cellulose, hydroxypropyl methylcellulose and mixtures thereof; and iii) optionally, a plasticizer selected from, oligomers, copolymers, oils, low molecular weight polyols having aliphatic hydroxyls, glycol ethers, poly(propylene glycol), multi-block polymers, single block polymers, triacetin, propylene glycol, glycerin, ethylene glycol, 1,2-butylene glycol, 2,3-butylene glycol, styrene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, poly(ethylene glycol) compounds, monopropylene glycol monoisopropyl ether, propylene glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl, ether, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, dibutylsebacate, acetyltributylcitrate, triethyl citrate, acetyl triethyl citrate, tributyl citrate, allyl glycolate and mixtures thereof; and c) optionally a polymer based nonfunctional coat. 2. An extended release tablet formulation according to claim 1, wherein said tablet exhibiting a value of (AUC.sub.fed)/(AUC.sub.fasted) of at least 0.80 with a lower 90% confidence limit of at least 0.75. 3. An extended release tablet formulation according to claim 1, wherein said tablet is coated with a functional coat of about 1% to 15% w/w of the tablet weight comprising a combination of a water non-dispersible polymer and a water dispersible polymer. 4. An extended release tablet formulation according to claim 1, wherein when orally administered to a patient in need thereof provides a peak plasma level of levetiracetam in from about eight to about sixteen hours and provides extended therapeutically effective plasma levels over a twenty four hour period with diminished incidences of neuropsychiatric adverse events by eliminating the troughs and peaks of drug concentration in vivo. 5. An extended release tablet according to claim 1, wherein the tablet is comprised of from about 50% to 80% levetiracetam w/w of the tablet and about 20% to about 40% w/w of the tablet hydroxypropyl methylcellulose. 6. An extended release tablet according to claim 5, wherein the tablet further comprises about 1% to about 5% w/w of the tablet povidone. 7. An extended release tablet according to claim 6, wherein the tablet is coated with a functional coat comprising ethyl cellulose, hydroxypropyl methylcellulose and polyethylene glycol. 8. An extended release tablet according to claim 1, wherein the tablet is coated with a functional coat of about 1% to about 12% w/w of the tablet weight, said functional coat comprising of from about 70% to about 80% w/w of the functional coat of ethyl cellulose, from about 20% to about 30% w/w of the functional coat of hydroxypropyl methylcellulose and from 10 to about 20% w/w of the functional coat of polyethylene glycol. 9. An extended release tablet according to claim 1 wherein the tablet is coated with a functional coat of about 1% w/w to about 12% w/w of the tablet weight, said functional coat comprising of from about 70% to about 80% w/w of the functional coat of ethyl cellulose and from about 20% to about 30% w/w of the functional coat of lactose. 10. An extended release tablet according to claim 1 having the following dissolution profile in USP Apparatus 1 (basket) at 100 rpm in purified water at 37.degree. C.: TABLE-US-00018 Time (hours) Average % Levetiracetam released 2 <35 4 35 75 12 >75 11. An extended release tablet according to claim 1, wherein the tablet is comprised of from about 61% to 73% w/w of the tablet levetiracetam and about 25% to about 35% w/w of the tablet hydroxypropyl methylcellulose. 12. An extended release tablet according to claim 11, wherein the tablet further comprises from about 1.1% to about 1.5% w/w of the tablet povidone. 13. An extended release tablet according to claim 11, wherein the tablet is coated with a functional coat of about 1.0% to about 6.0% w/w of the tablet, said functional coat comprising of about 75% w/w of the functional coat of ethyl cellulose and about 25% w/w of the functional coat of hydroxypropyl methylcellulose. 14. An extended release tablet according to claim 11, wherein the tablet is coated with a functional coat comprising of ethyl cellulose, hydroxypropyl methylcellulose and polyethylene glycol. 15. An extended release tablet according to claim 1, wherein said tablet is coated with a functional coat of about 1-6% w/w of the tablet. 16. An extended release tablet according to claim 15, wherein the functional coat comprises of ethyl cellulose having a 44.0-51.0% content of ethoxy groups and hydroxypropyl methylcellulose having viscosity of 2-6 cps at 2% aqueous solution with a methoxy content of 28.0-30.0% and a hydroxypropoxy group content of 7.0-12.0%. 17. An extended release tablet according to claim 1, wherein the tablet is prepared by wet granulation, dry granulation or direct compression. 18. An extended release tablet according to claim 1, wherein the tablet is prepared by wet granulation, dry granulation or direct compression and the core is coated either in a coating pan or in a fluidized bed system. 19. The extended release tablet of claim 1 wherein the tablet comprises a polymer-based nonfunctional coat comprising hydrophilic film forming polymer, suitable colorant and opacifying agent. 20. An extended release tablet of levetiracetam according to claim 1 consisting of levetiracetam, povidone, hydroxypropyl methylcellulose with a methoxy content of 19.0-24.0%, colloidal silicon dioxide, magnesium stearate, talc, ethyl cellulose, polyethylene glycol and hydroxypropyl methylcellulose with a methoxy content of 28.0-30.0%. 21. The extended release tablet of levetiracetam according to claim 1, wherein levetiracetam is present in an amount of about 67% w/w, povidone is present in an amount of about 1% w/w, hydroxypropyl methylcellulose with a methoxy content of 19.0-24.0% is present in an amount of about 26% w/w, colloidal silicon dioxide is present in an amount of about 1% w/w, magnesium stearate is present in an amount of about 1% w/w, talc is present in an amount of about 1% w/w, ethyl cellulose is present in an amount of about 2% w/w, polyethylene glycol is present in an amount of about 1% w/w and hydroxypropyl methylcellulose with a methoxy content of 28.0-30.0% is present in an amount of about 1% w/w.