Novel sterilization process for pharmaceutical suspensions

A - Human Necessities – 61 – L

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Details

IPC codes

A61L 2/04 (2006.01) A61K 9/10 (2006.01) A61K 31/56 (2006.01) A61L 2/00 (2006.01)

Type

Patent

Patent number

CA 2310698

Description

The invention is directed to a method for sterilizng a pharmaceutical formulation comprising a suspension of a water-insoluble pharmaceutical, comprising the steps of heat-sterilizing an aqueous solution of a viscosity enhancer, to result in a first sterile premix. Next is sterile-filtering an aqueous solution of a mixture of a pharmaceutically-active compound, which results in a second sterile pre-mix. Next is heat-sterilizing a mixture of water, a water-insoluble pharmaceutical, and at least a partial amount of an electrolyte to provide a sub-saturated solution of the electrolyte, and adding under aseptic conditions an aqueous surfactant, to give a third sterile pre- mix. Finally, combining all three pre-mixes in sterile fashion to achieve a sterile suspended pharmaceutical formulation. Thus, for the third pre-mix, use of either Sodium chloride (in varying proportion) or Sodium acetate (in one proportion, but not limited to) is given as an example. The invention is also directed to methods for making sterile suspensions of pharmaceutically active compositions including Ciprofloxacin and hydrocortisone, and pharmaceutical compositions made according to this process.

L'invention concerne un procédé qui permet de stériliser une formulation pharmaceutique comprenant une suspension d'une substance pharmaceutique insoluble dans l'eau. Selon le procédé, on stérilise par la chaleur une solution aqueuse d'un agent augmentant la viscosité, de façon à obtenir un premier prémélange stérile. On stérilise par filtration une solution aqueuse d'un mélange d'un composé pharmaceutiquement actif, de façon à obtenir un deuxième prémélange stérile. On stérilise par la chaleur un mélange constitué d'eau, d'une substance pharmaceutique insoluble dans l'eau et d'au moins une quantité partielle d'un électrolyte, de façon à obtenir une solution subsaturée dudit électrolyte, puis on ajoute dans des conditions aseptiques un tensioactif aqueux, de façon à obtenir un troisième prémélange stérile. Pour finir, on combine les trois prémélanges d'une manière stérile de façon à obtenir une formulation pharmaceutique en suspension stérile. On utilise par exemple, comme troisième prémélange, du chlorure de sodium (dans diverses proportions) ou de l'acétate de sodium (dans une seule proportion, mais sans s'y limiter). L'invention concerne également des procédés qui permettent de préparer des suspensions stériles de compositions pharmaceutiquement actives renfermant de la ciprofloxacine et de l'hydrocortisone, ainsi que des compositions pharmaceutiques préparées selon lesdits procédés.

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