Pharmaceutical forms with improved pharmacokinetic properties

• US 8,613,950 B2
• Filed: 02/16/2006
• Issued: 12/24/2013
• Est. Priority Date: 03/01/2005
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Serno, Peter, Heinig, Roland, Pauli, Kerstin, Hayauchi, Yutaka
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US11/885,019
• Publication Number:
  US 20080249096A1
• Time in Patent Office: 2,868 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present application relates to novel drug formulations of vardenafil which dissolve rapidly in the mouth and lead to increased bioavailability and to a plateau-like plasma concentration profile, and to processes for their preparation.

Claims

1. A drug formulation of vardenafil which disintegrates rapidly in the mouth, comprising:

an uncoated tablet which disintegrates rapidly in the mouth and which releases the vardenafil in the mouth without swallowing the tablet, said tablet comprising vardenafil hydrochloride trihydrate, and

at least one sugar alcohol,

and wherein at least 80% of the vardenafil hydrochloride trihydrate in the drug formulation dissolves at 25°

C. in 10 ml of physiological saline, and further wherein the rate of release of the vardenafil hydrochloride trihydrate from the drug formulation in 900 ml of physiological saline within the first 5 minutes in the USP pedal stirrer apparatus at 50 rotations per minute at 37°

C. is at least 70%.

2. The drug formulation according to claim 1, wherein the vardenafil hydrochloride trihydrate is in micronized form with a mean particle size of less than 20 μ

m.

3. The drug formulation according to claim 1 or claim 2, wherein said sugar alcohol comprises from 40% to 99% of the total formulation.

4. The drug formulation according to claim 1 or 2, wherein said sugar alcohol is selected from the group consisting of sorbitol, mannitol and mixtures thereof.

5. The drug formulation according to claim 4, wherein said sugar alcohol is mannitol.

6. The drug formulation of claim 4, wherein said sugar alcohol is sorbitol.

7. The drug formulation according to claim 4, wherein said vardenafil hydrochloride trihydrate comprises from 0.8% to 25% of the formulation, calculated as vardenafil free base.

18. The drug formulation of claim 4, wherein said sugar alcohol is a mixture of mannitol and sorbitol.

8. A drug formulation in the form of an uncoated tablet which disintegrates rapidly in the mouth and releases the drug in the mouth without swallowing the tablet comprising

vardenafil hydrochloride trihydrate, and

at least two sugar alcohols.

9. The drug formulation according to claim 8, wherein said sugar alcohols are a mixture of sorbitol and mannitol.

10. The drug formulation according to claim 8, wherein at least one sugar alcohol is mannitol.

11. The drug formulation of claim 8, wherein at least one sugar alcohol is sorbitol.

12. The drug formulation according to claim 8, wherein said vardenafil hydrochloride trihydrate comprises from 0.8% to 25% of the formulation, calculated as vardenafil free base.

13. The drug formulation according to claim 8, wherein at least 80% of the vardenafil hydrochloride trihydrate in the drug formulation dissolves at 25°

C. in 10 ml of physiological saline.

14. The drug formulation according to claim 8, wherein the rate of release of the vardenafil hydrochloride trihydrate from the drug formulation in 900 ml of physiological saline within the first 5 minutes in the USP pedal stirrer apparatus at 50 rotations per minute at 37°

C. is at least 70%.

15. The drug formulation according to claim 8, wherein at least 80% of the vardenafil hydrochloride trihydrate in the drug formulation dissolves at 25°

C. in 10 ml of physiological saline and the rate of release of the vardenafil from the drug formulation in 900 ml of physiological saline within the first 5 minutes in the USP pedal stirrer apparatus at 50 rotations per minute at 37°

C. is at least 70%.

16. The drug formulation according to claim 8 or 12, comprising from 40% to 99% sugar alcohol of the total formulation.

17. A drug formulation in the form of an uncoated tablet which disintegrates rapidly in the mouth and releases vardenafil hydrochloride trihydrate in the mouth without swallowing the tablet, said tablet comprising

vardenafil hydrochloride trihydrate;

sorbitol; and

mannitol; and

wherein;

said vardenafil hydrochloride trihydrate is in micronized form with a mean particle size of less than 20 μ

m;

said vardenafil hydrochloride trihydrate comprises from 0.8% to 25% of the formulation, calculated as vardenafil free base; and

said sorbitol and mannitol together comprises from 40% to 99% of the formulation.