Sublingual oral dosage form

• US 6,572,891 B1
• Filed: 09/08/2000
• Issued: 06/03/2003
• Est. Priority Date: 10/23/1999
• Status: Expired due to Term

• Current Assignee: Alkaloid A.D.
• Original Assignee: Alkaloid A.D.
• Inventors: Ugarkovic, Sonja Jovan
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): DeWitty, Robert M
• Application Number:
  US09/658,205
• Time in Patent Office: 998 Days
• Field of Search: 424/489, 514/282, 229/206
• US Class Current: 424/489
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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

Abstract

A pharmaceutical sublingual solid dosage form comprising a morphine salt together with excipients including a saccharide, a binder and a disintegrant. A method of manufacturing the dosage form is also described, together with packaging suitable for long term storage of the dosage form.

Claims

1. A pharmaceutical sublingual solid dosage form comprising:

(a) a therapeutically effective amount of an active ingredient consisting essentially of a salt of morphine, diamorphine or oxycodone or a mixture thereof;

(b) one or more saccharides as fillers;

(c) from 0.6 to 1.8% by weight of gelatin; and

(d) from 0.1 to 10% by weight of a disintegrant;

said solid dosage form releasing 90% of said salt when placed in 500 cm³ of distilled water for 5 minutes at 37°

C. using the apparatus specified in USP23 with a basket run at a speed of 100 rpm.

2. A dosage form as claimed in claim 1, wherein the morphine salt is morphine sulphate pentahydrate.

3. A dosage form as claimed in claim 1, wherein the salt of diamorphine is diamorphine hydrochloride.

4. A dosage form as claimed in claim 1, wherein the filler comprises a soluble saccharide selected from the group consisting of mannitol, lactose, xylitol and mixtures thereof.

5. A dosage form as claimed in claim 4, comprising 20 to 40% by weight of mannitol and 30 to 60% by weight of lactose.

6. A dosage form as claimed in claim 1, wherein the amount of gelatin is 0.8 to 1.5% by weight.

7. A dosage form as claimed in claim 1, comprising granulates compacted by wet granulation.

17. A dosage form as claimed in claim 1 wherein the salt of oxycodone is oxycodone hydrochloride.

8. A method of treating chronic pain by administering a therapeutically effective amount of an active ingredient consisting essentially of a salt of morphine, diamorphine or oxycodone or a mixture thereof in the form of a sublingual tablet,

said sublingual tablet additionally comprising:

(a) from 0.6 to 1.8% by weight of gelatin; and

(b) from 0.1 to 10% by weight of a disintegrant;

said sublingual tablet releasing 90% of said salt when placed in 500 cm³ of distilled water for 5 minutes at 37°

C. using the apparatus specified in USP23 with a basket run at a speed of 100 rpm.

9. A method for administering morphine to a patient in need thereof comprising the step of sublingually administering a dosage form to the patient, the dosage form comprising:

(a) a therapeutically effective amount of an active ingredient consisting essentially of morphine sulphate pentahydrate;

(b) a filler comprising at least one saccharide;

(c) from 0.6 to 1.8% by weight of gelatin; and

(d) from 0.1 to 10% by weight of a disintegrant;

said solid dosage form releasing 90% of said morphine sulphate pentahydrate when placed in 500 cm³ of distilled water for 5 minutes at 37°

C. using the apparatus specified in USP23 with a basket run at a speed of 100 rpm.

10. The method of claim 9, wherein the filler comprises a saccharide selected from the group consisting of mannitol, lactose, xylitol, and mixtures thereof.

11. The method of claim 10, wherein the dosage form comprises 20 to 40% by weight of mannitol and 30 to 60% by weight of lactose, based upon 100% total weight of dosage form.

12. The method of claim 9, wherein the dosage form comprises granulates of morphine sulphate pentahydrate compacted by wet granulation.

13. The method of claim 9, wherein at least 90% of the morphine sulphate pentahydrate is released in 2 minutes or less.

14. A pharmaceutical sublingual solid dosage form comprising:

(a) a therapeutically effective amount of an active ingredient consisting essentially of a salt of morphine, diamorphine or oxycodone or a mixture thereof;

(b) from 20 to 40% by weight of mannitol;

(c) from 30 to 60% by weight of lactose;

(d) from 0.6 to 1.8% by weight of gelatin; and

(e) from 0.1 to 10% by weight of a disintegrant;

said solid dosage form releasing 90% of said salt when placed in 500 cm³ of distilled water for 5 minutes at 37°

C. using the apparatus specified in USP23 with a basket run at a speed of 100 rpm.

15. The pharmaceutical sublingual solid dosage form according to claim 14 wherein the salt of morphine is morphine sulphate pentahydrate.

16. The pharmaceutical sublingual solid dosage form according to claim 15, wherein at least 90% of the morphine sulphate pentahydrate is released in 2 minutes or less.