Orodispersible dosage forms of desmopressin acetate

• US 7,560,429 B2
• Filed: 05/07/2003
• Issued: 07/14/2009
• Est. Priority Date: 05/07/2002
• Status: Expired due to Term

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Lindner, Hans, Wittendorff, Jorgen, Nilsson, Anders
• Primary Examiner(s): Gupta; Anish
• Application Number:
  US10/513,437
• Publication Number:
  US 20050232997A1
• Time in Patent Office: 2,260 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• 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 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2063 Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10

Abstract

Good bioavailability of desmopressin can be obtained by means of an orodispersible pharmaceutical dosage form. Preferred dosage forms comprise desmopressin and an open matrix network which is an inert water-soluble or water-dispersible carrier material. Desmopressin formulated in this way is useful for voiding postponement, or the treatment or prevention of incontinence, primary nocturnal enuresis (PNE), nocturia or central diabetes insipidus. Peptides other than desmopressin can also be formulated in this way.

Claims

1. An orodispersible solid pharmaceutical dosage form of desmopressin acetate, wherein said dosage form (A) disintegrates in the mouth within 10 seconds and (B) comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g.

2. A dosage form as claimed in claim 1, wherein the dosage form comprises desmopressin acetate and an open matrix network carrying the desmopressin acetate, wherein the open matrix network is comprised of a water-soluble or water-dispersible carrier material that is inert towards desmopressin acetate.

3. A dosage form as claimed in claim 2, wherein the open matrix network comprises gelatin.

4. A dosage form as claimed in claim 3, wherein the gelatin is fish gelatin.

5. A dosage form as claimed in claim 4, wherein the fish gelatin is non-gelling.

6. A process for preparing an orodispersible solid pharmaceutical dosage form of desmopressin acetate which disintegrates in the mouth within 10 seconds and which comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g, said process comprising subliming solvent from a composition comprising desmopressin acetate and a solution of carrier material in the solvent, wherein the composition is in the solid state in a mold.

7. A process as claimed in claim 6, wherein the subliming is carried out by freeze drying the composition.

8. A process as claimed in claim 6, wherein the solvent is water.

9. A process as claimed in claim 6, wherein the pH of the solution is within the range of from 3 to 6.

13. A process as claimed in claim 6, wherein the pH of the solution is within the range of from 3.5 to 5.5.

14. A process as claimed in claim 6, wherein the pH of the solution is within the range of from 4 to 5.

10. A method of treating a disease or condition selected from the group consisting of incontinence, primary nocturnal enuresis (PNE), nocturia and central diabetes insipidus, comprising administering to a subject an effective and generally non-toxic amount of desmopressin acetate in an orodispersible solid pharmaceutical dosage form, wherein said dosage form (A) disintegrates in the mouth within 10 seconds and (B) comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g.

11. A packaged dosage form of desmopressin acetate comprising an orodispersible solid pharmaceutical dosage form of desmopressin acetate, wherein said dosage form disintegrates in the mouth within 10 seconds, and wherein said dosage form comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g, together with instructions to place the dosage form in a subject'"'"'s mouth.

12. A method for preparing a packaged dosage form of desmopressin acetate, the method comprising bringing into association an orodispersible solid pharmaceutical dosage form of desmopressin acetate, wherein said dosage form disintegrates in the mouth within 10 seconds, and wherein said dosage form comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g, and instructions to place the dosage form in a subject'"'"'s mouth.

15. An orodispersible solid pharmaceutical dosage form of desmopressin acetate, wherein said dosage form (i) disintegrates in the mouth within 10 seconds, (ii) comprises an amount of desmopressin, measured as the free base, selected from the group consisting of 25 μ

g, 50 μ

g and 75 μ

g, and (iii) is prepared by a process comprising subliming solvent from a composition comprising desmopressin acetate and a solution of carrier material in the solvent, wherein the composition is in the solid state in a mold.

16. A dosage form as claimed in claim 15, wherein the subliming is carried out by freeze drying the composition.

17. A dosage form as claimed in claim 15, wherein the solvent is water.

18. A dosage form as claimed in claim 15, wherein the pH of the solution is within the range of from 3 to 6.

19. A dosage form as claimed in claim 15, wherein the pH of the solution is within the range of from 4 to 5.