Claims for Patent: 8,999,393

Summary for Patent: 8,999,393

Title:	Sustained release formulations of lorazepam
Abstract:	A pharmaceutical composition for delivering lorazepam in a prolonged fashion is achieved with prolonged release lorazepam pharmaceutical beads. The composition typically contains sustained release lorazepam beads and delayed sustained release lorazepam beads. The composition can provide once daily dosing that maintains 24 hour therapeutic effect under steady state conditions.
Inventor(s):	Saltel; Douglas A. (Austin, TX), Vachon; Michael (Quebec, CA)
Assignee:	Edgemont Pharmaceuticals LLC (Austin, TX)
Application Number:	14/150,375
Patent Claims:	1. A pharmaceutical composition, comprising (i) lorazepam sustained release beads and (ii) lorazepam delayed sustained release beads, wherein the total amount of lorazepam contained in said composition is 0.5 mg to 10 mg and wherein said composition when administered once daily provides (1) a lorazepam blood plasma steady state Cmax that is +/-35% of the Cmax achieved by immediate release tablets given twice daily and having the same total daily amount of lorazepam, and/or (2) a lorazepam blood plasma steady state Cmin that is +/-35% of the Cmin achieved by immediate release tablets given b.i.d. and having the same total daily amount of lorazepam. 2. The pharmaceutical composition according to claim 1, wherein said composition, when administered once daily to a patient, maintains a therapeutic effect for at least 24 hours. 3. The pharmaceutical composition according to claim 1, wherein 100% of the lorazepam in said composition is contained in the combination of said sustained release beads and said delayed sustained release beads. 4. The pharmaceutical composition according to claim 1, wherein said sustained release beads have a dissolution profile in a two media in vitro dissolution test such that from 20 70% of the lorazepam is released in 2 hours; and wherein said two media in vitro dissolution test is carried out for two hours in a media that comprises 0.1 N HCl and then is carried out in a media that comprises a phosphate buffer and has a pH of 7.4. 5. The pharmaceutical composition according to claim 4, wherein said dissolution profile further includes the release of 50% of the lorazepam within 1 to 5 hours. 6. The pharmaceutical composition according to claim 4, wherein said dissolution profile further includes that 90% of the lorazepam is not released before 10 hours. 7. The pharmaceutical composition according to claim 1, wherein said lorazepam delayed sustained release beads have a dissolution profile in a two media in vitro dissolution test such that the release of 90% of the lorazepam occurs after 10 hours; and wherein said two media in vitro dissolution test is carried out for two hours in a media that comprises 0.1 N HCl and then is carried out in a media that comprises a phosphate buffer and has a pH of 7.4. 8. The pharmaceutical composition according to claim 1, wherein said delayed sustained release beads contain a delay coating that is pH-dependent and wherein said delayed sustained release beads have a dissolution profile in a two media in vitro dissolution test such that from 20 80% of the lorazepam is released in 4 hours; and wherein said two media in vitro dissolution test is carried out for two hours in a media that comprises 0.1 N HCl and then is carried out in a media that comprises a phosphate buffer and has a pH of 7.4. 9. The pharmaceutical composition according to claim 1, wherein said sustained release beads comprise lorazepam dispersed in a polymer matrix and wherein said delayed sustained release beads comprise a core having lorazepam dispersed in a polymer matrix and an enteric coating surrounding said core. 10. The pharmaceutical composition according to claim 2, wherein said sustained release beads comprise lorazepam dispersed in a polymer matrix and wherein said delayed sustained release beads comprise a core having lorazepam dispersed in a polymer matrix and an enteric coating surrounding said core. 11. The pharmaceutical composition according to claim 9, wherein said polymer matrix in the sustained release beads and in the delayed sustained release beads comprises hydroxypropyl methylcellulose (HPMC). 12. The pharmaceutical composition according to claim 11, wherein said enteric coating is designed to release a drug at pH 7 or greater. 13. The pharmaceutical composition according to claim 1, wherein said composition provides, when dosed once daily, a lorazepam blood plasma steady state Cmax of not greater than 12 ng/ml for each 1 mg of lorazepam, and/or a lorazepam blood plasma steady state Cmin of at least 5 ng/ml for each 1 mg of lorazepam. 14. The pharmaceutical composition according to claim 1, wherein said composition when administered once daily provides (1) a lorazepam blood plasma steady state Cmax that is +/-20% of the Cmax achieved by immediate release tablets given twice daily and having the same total daily amount of lorazepam, and/or (2) a lorazepam blood plasma steady state Cmin that is +/-20% of the Cmin achieved by immediate release tablets given b.i.d. and having the same total daily amount of lorazepam. 15. The pharmaceutical composition according to claim 1, wherein said composition exhibits continued release of lorazepam for at least 24 hours, as determined in single dose pharmacokinetic study. 16. A sustained release lorazepam pharmaceutical composition, which comprises lorazepam prolonged release beads, wherein said composition has a single dose pharmacokinetic profile that comprises a T.sub.max at 4 hours or longer and continued release of lorazepam beyond 20 hours; and wherein said composition being an oral dosage form containing from 0.5 mg to 10 mg of lorazepam and when administered once daily to a patient maintains a therapeutic effect for at least 24 hours. 17. The composition according to claim 16, wherein said pharmacokinetic profile includes the continued release of lorazepam for at least 24 hours. 18. The composition according to claim 17, wherein said pharmacokinetic profile includes the continued release of lorazepam for at least 28 hours. 19. The composition according to claim 16, wherein said pharmacokinetic profile provides during 0-24 hours from 40 to 60% of AUC during 0-120 hours. 20. A method for treating a lorazepam-treatable condition in a patient, which comprises administering once a day to a patient in need thereof a pharmaceutical composition according to claim 1 in a sufficient dose to provide 24 hour therapeutic effect during steady state conditions.