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1. WO2021063468 - COMPOSITION PHARMACEUTIQUE PARENTÉRALE STABLE CONTENANT DE LA TIGÉCYCLINE ET SON PROCÉDÉ DE PRÉPARATION

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

CLAIMS

1. A stable pharmaceutical composition for parenteral administration comprising a therapeutically effective quantity of tigecycline or a pharmaceutically acceptable salt or derivative thereof, as an active ingredient and an effective quantity of trehalose as a stabilizer in order to prevent the degradation and improve the physicochemical stability of the active ingredient in the finished dosage form.

2. The pharmaceutical composition according to claim 1, wherein the ratio of tigecycline to trehalose is from 1 : 1 to 1 :5, preferably from 1 :2 to 1 :4 and most preferably 1 :2.

3. The pharmaceutical composition according to claim 2, wherein said composition has a pH value from 4.5 to 5.5.

4. The pharmaceutical composition according to claim 1, wherein it further comprises at least one pharmaceutically acceptable excipient such as Raffinose.

5. The pharmaceutical composition according to any preceding claim, wherein the amount of tigecycline in said composition is in the range of 15-50% by weight % of the total weight of the composition.

6. The pharmaceutical composition according to claim 4, wherein the amount of tigecycline to raffinose and to trehalose is about 1 : 0.66 : 1.34.

7. The pharmaceutical composition according to any preceding claim, wherein the tigecycline used is tigecycline amorphous.

8. A process for the preparation of a stable pharmaceutical composition for parenteral administration comprising a therapeutically effective quantity of tigecycline or a pharmaceutically acceptable salt or derivative thereof, as an active ingredient, and an effective quantity of trehalose in order to prevent the degradation and improve the physicochemical stability of the active ingredient in the finished dosage form, wherein said process comprises following steps:

a) Dissolving the total quantity of trehalose in water for injection and stirring for appropriate time until complete dissolution, wherein said solution preparation is performed at a temperature ranging from TC to 8°C and under Nitrogen purging in the compounding vessel;

b) The solution pH is adjusted to acidic pH value with suitable Hydrochloric acid solution; c) The total quantity of Tigecycline or salt or derivative thereof, is added slowly to the resulting solution of step b) and stirred for appropriate time until complete dissolved and the pH is adjusted to a pH value between 4.5 to 5.5 with suitable Hydrochloric acid or Sodium Hydroxide solution;

d) The solution volume is adjusted to the predetermined volume with water for injection;

e) The prepared bulk solution of step d) is aseptically filtered with suitable membrane filters; f) The filtered solution is filled in clear tubular Type I glass vials and semi-stoppered with butyl rubber stoppers for lyophilisation; and

g) The filled semi-stoppered vials are lyophilized according to the following parameters: the freezing stage is carried out at a temperature ranging from about -40°C to -45°C, the primary drying stage is carried out at a temperature ranging from about -35°C to 0°C, and at pressure

ranging from about O.lmbar to 0.3mbar and the secondary drying stage is carried out at a temperature ranging from about 25°C to 40°C, and at pressure ranging from O.lmbar to 0.3mbar.

9. The process for the preparation of a pharmaceutical composition according to claim 8, wherein the ratio of tigecycline to trehalose is from 1: 1 to 1:5, preferably from 1:2 to 1:4 and most preferably 1 :2.

10. The process for the preparation of a pharmaceutical composition according to claim 8, wherein said composition iurther comprises at least one pharmaceutically acceptable excipient such as Raffinose.

11. The process for the preparation of a pharmaceutical composition according to any preceding claim, wherein the tigecycline used is tigecycline amorphous.