PROGESTIN-CONTAINING DRUG DELIVERY SYSTEM

• US 20110293720A1
• Filed: 08/07/2009
• Published: 12/01/2011
• Est. Priority Date: 08/08/2008
• Status: Abandoned Application

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Bayer Schering Pharma AG (Bayer AG)
• Inventors: Bracht, Stefan, General, Sascha, Funke, Adrian, Terebesi, Ildikó
• Application Number:
  US13/057,299
• Publication Number:
  US 20110293720A1
• Time in Patent Office: Days
• US Class Current: 424/485
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention relates to drug delivery compositions in the form of thin water-soluble films (wafers), which contain small particles that comprise at least one progestin and at least one protective agent. The protective agent provides effective taste-masking of the progestin due to limited release of the progestin in the mouth. The progestin is hence not absorbed via the buccal route, but rather via the enteral (per-oral) route.

Claims

1. A unit dosage form comprising a thin water-soluble film matrix, wherein

a) said film matrix comprises at least one water-soluble matrix polymer;

b) said film matrix comprises particles where said particles comprises at least one progestin and at least one protective agent, and where said particles have a d₉₀ particle size of ≦

280 μ

m; and

c) said film matrix has a thickness of 300 μ

m.

2. The unit dosage form according claim 1, wherein said progestin is embedded in said protective agent.

3. The unit dosage form according to claim 2, wherein said progestin is present in a solid dispersion in said protective agent.

4. The unit dosage form according to claim 1, wherein said progestin is coated with said protective agent.

5. The unit dosage form according to claim 1, wherein said protective agent is a cationic polymethacrylate.

6. The unit dosage form according to claim 1, wherein said protective agent is a wax.

7. The unit dosage form according to claim 6, wherein said wax is carnauba wax.

8. The unit dosage form according to claim 1, wherein said particles have a d₉₀ particle size of 5.250 μ

m, such as a d₉₀ particle size of ≦

200 μ

m, preferably a d₉₀ particle size of 5.175 μ

m, such as a d₉₀ particle size of ≦

150 μ

m, e.g. a d₉₀ particle size of ≦

100 μ

m.

9. The unit dosage form according to claim 1, wherein said particles have a d₉₀ particle size in the range of from 30-280 μ

m, such as in the range of from 40-250 μ

m, e.g. in the range of from 50-200 μ

m or in the range of from 50-150 μ

m.

10. The unit dosage form according to claim 1, wherein said progestin is selected from the group consisting of levo-norgestrel, norgestrel, norethindrone (norethisterone), dienogest, norethindrone (norethisterone) acetate, ethynodiol diacetate, dydrogesterone, medroxyprogesterone acetate, norethynodrel, allylestrenol, lynestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, chlormadinone acetate, megestrol, promegestone, desogestrel, 3-keto-desogestrel, norgestimate, gestodene, tibolone, cyproterone acetate, dienogest and drospirenone.

11. The unit dosage form according to claim 10, wherein said progestin is selected from the group consisting of gestodene, dienogest and drospirenone.

12. The unit dosage form according to claim 11, wherein said unit dosage form comprises 0.25-5 mg drospirenone, such as 1-4 mg drospirenone, e.g. 2-4 mg drospirenone, preferably 2.5-3.5 mg drospirenone, most preferably about 3 mg drospirenone.

13. The unit dosage form according to claim 1, wherein said water-soluble matrix polymer is selected from the group consisting of a cellulosic material, a gum, a protein, a starch, a synthetic polymer, a glucan, and mixtures thereof.

14. The unit dosage form according to claim 1, wherein said film matrix has a thickness of ≦

250 μ

m, preferably ≦

200 μ

m, such as ≦

150 μ

m, more preferably ≦

120, such as ≦

100 μ

m.

15. The unit dosage form according to claim 14, wherein said film matrix has a thickness in the range of from 10-150 μ

m, such as 20-125 μ

m, e.g. 30-100 μ

m, preferably 35-90 μ

m, more preferably 40-80 μ

m.

16. The unit dosage form according to claim 1, wherein said unit dosage form further comprises at least one estrogen.

17. The unit dosage form according to claim 16, wherein

a) said film matrix comprises at least one water-soluble matrix polymer;

b) said film matrix comprises particles where said particles comprises at least one progestin, at least one estrogen and at least one protective agent, and where said particles have a d₉₀ particle size of ≦

280 μ

m; and

c) said film matrix has a thickness of ≦

300 μ

m.

18. The unit dosage form according to claim 16, wherein

a) said film matrix comprises at least one water-soluble matrix polymer;

b) said film matrix comprises particles where said particles comprises at least one progestin and at least one protective agent, and where said particles have a d₉₀ particle size of ≦

280 μ

m;

c) said film matrix comprises particles where said particles comprises at least one estrogen and at least one protective agent, and where said particles have a d₉₀ particle size of ≦

280 μ

m;

d) said film matrix has a thickness of ≦

300 μ

m.

19. The unit dosage form according to claim 16, wherein said film matrix comprises at least one surfactant.

20. The unit dosage form according to claim 16, wherein

a) said film matrix comprises at least one water-soluble matrix polymer, wherein at least one estrogen is dispersed in said water-soluble matrix polymer;

b) said film matrix comprises particles where said particles comprises at least one progestin and at least one protective agent, and where said particles have a d₉₀ particle size of ≦

280 μ

m; and

c) said film matrix has a thickness of 300 μ

m.

21. The unit dosage form according to claim 16, wherein said estrogen is selected from the group consisting of ethinylestradiol, estradiol including therapeutically acceptable derivates of estradiol, estrone, mestranol, estriol, estriol succinate and conjugated estrogens.

22. The unit dosage form according to claim 16, wherein less than 25% (w/w), preferably less than 20% (w/w), more preferably less than 15% (w/w), most preferably less than 5% (w/w) of the progestin is dissolved from the unit dosage form within 3 minutes when the unit dosage form is placed into a beaker with 10 ml of simulated saliva pH 6.0 at 37°

C. as dissolution medium.

23. The unit dosage form according to claim 16 for use as a medicament.

24. A unit dosage form according to claim 16 for the inhibition of ovulation in a female mammal.

25. A unit dosage form according to claim 16 for providing contraception in a female mammal.