Formulation comprising triethylenetetramine tetrahydrochloride

Abstract

This invention relates to pharmaceutical formulations comprising triethylenetetramine tetrahydrochloride (TETA.4HCl). Specifically, it relates to pharmaceutical compositions which are suitable for once a day administration to a subject in need of treatment.

Description

Abstract This invention relates to pharmaceutical formulations comprising triethylenetetramine tetrahydrochloride (TETA.4HCl). Specifically, it relates to pharmaceutical compositions suitable for once-daily use in patients requiring treatment.

Claims

CLAIMS1. A tablet dosage form comprising: triethylenetetramine tetrahydrochloride in an amount of from 60 to 95 wt%; and a first lubricant in an amount of from 0.1 to 10 wt%; wherein wt% amounts are relative to the total tablet weight.

2. A tablet dosage form according to claim 1 which comprises from 70 to 95 wt% triethylenetetramine tetrahydrochloride, preferably which comprises from 80 to 95 wt% triethylenetetramine tetrahydrochloride, more preferably from 80 to 90 wt% triethylenetetramine tetrahydrochloride, yet more preferably from 80 to 85 wt% tri ethyl enetetramine tetrahy drochl ori de .

3. A tablet dosage form according to claim 1 or claim 2, wherein the triethylenetetramine tetrahydrochloride comprises no more than 50 wt% triethylenetetramine tetrahydrochloride Form A and at least 50 wt% tri ethylenetetramine tetrahydrochloride Form B, wherein the wt% refers to the weight expressed as the total amount of triethylenetetramine tetrahydrochloride in the tablet dosage form.

4. A tablet dosage form according to any one of the preceding claims, which comprises from 70 to 95 wt%, preferably from 80 to 95 wt%, more preferably from 80 to 90 wt%, yet more preferably from 80 to 85 wt% triethylenetetramine tetrahydrochloride Form B.

5. A tablet dosage form according to any one of the preceding claims, wherein the first lubricant is selected from a fatty acid or a derivative thereof, a surfactant, an inorganic material or a polymer.

6. A tablet dosage form according to any one of the preceding claims, wherein:(a) the first lubricant is selected from talc and magnesium aluminium silicate, optionally wherein the tablet dosage form comprises the first lubricant in an amount of from 0.1 to 10 wt%; or(b) the first lubricant is selected from stearic acid, a metal stearate, sodium benzoate, a polyethylene oxide) and polypropylene oxide) co-polymer, polyethylene glycol, sodium dodecyl sulfate and vegetable oil, optionally wherein the tablet dosage form comprises the first lubricant in an amount of from 0.1 to 5 wt%.

7. A tablet dosage form according to any one of claims 1 to 6 wherein the first lubricant is a metal stearate; optionally wherein(a) the metal stearate is one or more selected from magnesium stearate, calcium stearate and zinc stearate; and further optionally wherein the metal stearate is magnesium stearate; and / or(b) the tablet dosage form comprises the first lubricant in an amount of from 0.1 to 0.3 wt%.

8. A tablet dosage form according to any one of claims 1 to 6, wherein the first lubricant is magnesium stearate and wherein the tablet dosage form comprises from 0.7 to 2.0mg magnesium stearate.

9. A tablet dosage form according to any one of the preceding claims, further comprising one or more fillers in an amount of from 5 to 39.9 wt%, optionally from 5 to 29.9 wt%, relative to the total tablet weight and one or more further excipients in an amount of 0 to 10 wt% relative to the total tablet weight.

10. A tablet dosage form according to claim 9, wherein the one or more fillers comprise mannitol, lactose, cellulose, microcrystalline cellulose, calcium carbonate, sorbitol, and / or starch, optionally wherein the one or more fillers comprise mannitol.

11. A tablet dosage form according to claim 9 or claim 10, which comprises from 5 to 15 wt% of one or more fillers, optionally from 9 to 15 wt% of one or more fillers.

12. A tablet dosage form according to claim 1, which consists of:(a) 70 to 95 wt% tri ethylenetetramine tetrahydrochloride;0.1 to 0.3 wt% magnesium stearate;5 to 29.9% wt% mannitol; and0 to 10 wt% one or more further excipients, wherein wt% amounts are relative to the total tablet weight; or(b) 80 to 90 wt% triethylenetetramine tetrahydrochloride;0.2 to 0.3 wt% magnesium stearate;5 to 15 wt% mannitol; and0 to 10 wt% one or more further excipients, wherein wt% amounts are relative to the total tablet weight; or(c) 80 to 85 wt% triethylenetetramine tetrahydrochloride;0.2 to 0.3 wt% magnesium stearate;9 to 15 wt% mannitol; and0 to 10 wt% one or more further excipients, wherein wt% amounts are relative to the total tablet weight.

13. A tablet dosage form according to any one of claims 9 to 12, wherein the one or more further excipients are selected from one or more stabilizers; one or more second lubricants; and / or one or more film coating excipients; optionally wherein the one or more second lubricants is glyceryl dibehenate and / or the one or more stabilizers is colloidal silicon dioxide.

14. A tablet dosage form according to claim 13, wherein the tablet comprises the one or more second lubricants in an amount of from 0.5 to 2.5 wt% relative to the total tablet weight; and / or the tablet comprises the one or more stabilizers in an amount of from 0.1 to 0.5 wt% relative to the total tablet weight; and / or the tablet is acoated tablet and comprises one or more film coating excipients in an amount of from 0.1 to 7.5 wt% relative to the total tablet weight.

15. A tablet dosage form according to any one of the preceding claims, wherein:(a) the tablet is a breakable tablet; and / or(b) the tablet has a hardness of from 300 to 360 N, optionally from 300 to 310 N; and / or(c) the tablet has a friability of less than 0.15 %; and / or(d) the tablet has a disintegration time of less than 5 minutes.

16. A tablet dosage form according to any one of the preceding claims for use in preventing or treating Wilson’s disease in a subject, optionally wherein the dosage form is administered to the subject once a day.

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