Composition and method for reducing adverse interactions between phenothiazine derivatives and plasma using cyclodextrins
AssigneeBaxter International Inc.
InventorJianwei Yu
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Abstract
Compositions and methods are provided for reducing adverse reactions as a result of parenteral administration of certain phenothiazine derivatives such as promethazine hydrochloride. The active compound may be admixed with an effective amount of one or more cyclodextrin derivatives, and if desired, one or more non-ionic surfactants such as the partial esters of sorbitol and the polyoxyethylene oxides of long chain fatty acids such as the polysorbates.
Claims38
A pharmaceutical composition suitable for parenteral administration, comprising:
- a) one or more phenothiazine derivatives;
- b) a beta- or gamma- cyclodextrin;
- and
- c) a polysorbate surfactant, wherein the combination of cyclodextrin and polysorbate synergistically inhibit precipitation caused by interaction of said one or more phenothiazine derivatives and plasma proteins.
The composition of claim 7, wherein said molar ratio is within the range of about 1:1 to about 1:3.
A pharmaceutical composition suitable for parenteral administration, comprising on a weight/volume (w/v) basis:
- a) from about 0.1 to about 70% of at least one member selected from the group consisting of phenothiazine derivatives;
- b) a beta- or gamma-cyclodextrin;
- and
- c) at least one non-ionic surfactant in an amount of from about 0.5% up to about 2% of said composition, said non-ionic surfactant being selected from the group consisting of polysorbates, wherein the combination of beta- or gamma- cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of the at least one member and plasma proteins.
An aqueous injectable solution, comprising promethazine hydrochloride, at least one cyclodextrin selected from the group consisting of beta- and gamma- cyclodextrins, wherein the molar ratio of promethazine hydrochloride to said cyclodextrin is within the range of about 1:0.5 to about 1:4, and at least one non-ionic surfactant selected from the group consisting of polysorbates, wherein the combination of cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of the phenothiazine hydrochloride and plasma proteins contained in the mammal.
A pharmaceutical composition suitable for parenteral administration, comprising on a weight/volume (w/v) basis:
- a) from about 1 to about 15% of promethazine hydrochloride;
- b) from about 5 to about 60% of beta-cyclodextrin, wherein the molar ratio of said promethazine hydrochloride to said beta-cyclodextrin is within the range of about 1:1 to about 1:3;
- and
- c) from 0.5% to about 2% of at least one non-ionic surfactant selected from the group consisting of polysorbates, wherein the combination of beta-cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of said phenothiazine hydrochloride and plasma proteins.
A method of reducing the formation of precipitates during parenteral administration of a promethazine hydrochloride solution to a mammal, the method comprising:
- adding at least one beta- or gamma- cyclodextrin to said solution, and adding at least one non-ionic surfactant to said solution, said at least one non-ionic surfactant being selected from the group consisting of polysorbates, wherein the combination of cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of phenothiazine hydrochloride and plasma proteins.
A method for reducing the formation of precipitates during injectable treatment which comprises administering to a mammal a composition comprising at least one phenothiazine derivative, at least one cyclodextrin selected from the group consisting of beta- and gamma- cyclodextrins and at least one non-ionic surfactant selected from the group consisting of polysorbates, wherein the combination of cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of the at least one phenothiazine derivative and plasma proteins contained in the mammal.
A method for reducing the quantity of beta- or gamma- cyclodextrin necessary to inhibit precipitate formation when a promethazine hydrochloride solution is administered to a patient, the method comprising adding at least one non-ionic surfactant selected from the group consisting of the polysorbates along with said beta- or gamma- cyclodextrin to said solution, wherein the combination of cyclodextrin and at least one non-ionic surfactant synergistically inhibit precipitation caused by interaction of the phenothiazine hydrochloride and plasma proteins contained in the patient.
Dependencies are inferred from the claim text.