Patent EA-002595-B1 (EA)
Title: Pharmaceutical formulation comprising amoxocylin and clavulanate, process for preparing the same and granulate comprising amoxocylin and clavulanate
Inventor: MENTION JACKY ANDRE GUSTAVE
IPC: A61K31/43
Filed: 1998-02-10
Abstract: 1. A pharmaceutical formulation comprising amoxycillin and clavulanate in a ratio of n: 1 where n is a number from 1 to 16 which comprises: a first set of granulates comprising amoxycillin and clavulanate in a ratio from 1:1 or 2:1; and a second set of granulates comprising amoxycillin and no clavulanate; providing to give an overall ratio between amoxycillin and clavulanate of n: 1, wherein the formulation when in the form of a tablet comprises the first and the second sets of granulates in a mixture. 2. A formulation as claimed in claim 1 in which n is 2, 4, 6, 7, 8, 14 or 16. 3. A formulation as claimed in claims 1 or 2 in which amoxycillin is present as amoxycillin trihydrate. 4. A formulation as claimed in any one of claims 1 to 3 in which clavulanate is present as potassium clavulanate. 5. A formulation as claimed in any one of claims 1 to 4 in which the granulates comprises an intragranular disintegrant in an amount from 1,25 to 3,5% by the granulate weight. 6. A formulation as claimed in any one of claims 1 to 5 in which the first set of granulates further comprises intragranular disintegrant as a silica gel in an amount from 5 to 25% by the clavulanate weight. 7. A formulation as claimed in any one of claims 1 to 6 in which the first set of granulates consist essentially of amoxycillin, potassium clavulanate, silica gel and an intragranular disintegrant. 8. A formulation as claimed in any one of claims 1 to 6 in which the second set of granulates consist essentially of amoxycillin and an intragranular disintegrant. 9. A formulation as claimed in any one of claims 5 to 8 in which the intragranular disintegrant is cross-linked N-vinyl-2-pyrrolidone or sodium starch glycollate. 10. A formulation as claimed in any one of claims 1 to 9 in the form of a tablet. 11. A formulation as claimed in claim 10 further comprising an extragranular excipient which is low-substituted hydroxyproylcellulose. 12. A formulation as claimed in claim 10 or 11 in which the combined weight of all excipients is less than 20% of the uncoated core weight of the tablet. 13. A formulation as claimed in claim 10, which comprises: amoxycillin granulates which consist essentially of amoxycillin trihydrate present in about 97wt% and CLPVP present in about 3wt%; amoxycillin and potassium clavulanate granulates which comprise a 2:1 ratio of amoxycillin to clavulanate, silica gel present in about 10 wt% of potassium clavulanate and about 3wt% of CLPVP; and extragranular excipients selected from the group including silica gel; low-substituted hydroxypropylcellulose or CLPVP; colloidal silica and magnesium stearate. 14. A formualtion as claimed in claim 12 in which the tablet cores have the weights: 500/125mg - 800 to 850mg; and  875/125mg - 1250 to 1350mg. 15. A formulation as claimed in any one of claims 1 to 9 in the form of a sachet or a powder for reconstitution as an aqueous syrup. 16. A process for preparing a formulation according to any one of the preceding claims which comprises blending together a first set of granulates comprising amoxycillin and clavulanate with a second set of granulates comprising amoxycillin and no clavulanate in an appropriate ratio with other excipients and then, if necessary and desired, further processing the blend to obtain the final desired formulation. 17. A process as claimed in claim 16 which comprises the preliminary step of preparing the first and/or second set of granulates by roller compaction. 18. A granulate comprising amoxycillin and no clavulanate in a ratio 2:1, which includes intragranular disintegrant in an amount from 5 to 25% by the clavulanate weight. 19. A granulate as claimed in claim 18 in which intragranular disintegrant is silica gel. 20. A granulate as claimed in claim 18 or 19 which further comprises intragranular disintegrant in an amount from 1,25 to 3,5% by the granulate weight. 21. A granulate as claimed in any claims 18 to 20 in which the granulates consist essentially of amoxycillin, potassium clavulanate, silicagel and an intragranular disintegrant. 22. A granulate as claimed in any claims 18 to 20 in which the intragranular disintegrant is cross-linked N-vinyl-2-pyrrolidone or sodium starch glycollate.