Stable bortezomib formulations
First Claim
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1. A storage-stable liquid pharmaceutical composition that includes bortezomib in a therapeutically effective amount, the composition comprising:
- a single-phase liquid formulation comprising a substantially non-aqueous solvent system suitable for injection, an aqueous acetate buffer, and bortezomib, wherein the bortezomib is present in the formulation at a therapeutically effective concentration;
wherein the solvent system comprises as a predominant component propylene glycol, and wherein the buffer has a pH of 3; and
wherein the solvent system, the buffer, and the pH are selected such as to be effective to suppress formation of at least one of an amide degradation product, a first carbinolamide degradation product, and a second carbinolamide degradation product when the liquid formulation is stored under storage conditions.
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Abstract
Multi-dose formulations for bortezomib are presented in which bortezomib has significantly improved stability. Especially preferred formulations include those in which bortezomib is in a liquid form suitable for injection, wherein the solvent system predominantly comprises propylene glycol. In other preferred aspects, bortezomib is present as a Lewis donor-acceptor complex with a hetero-bifunctional Lewis base.
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Citations
15 Claims
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1. A storage-stable liquid pharmaceutical composition that includes bortezomib in a therapeutically effective amount, the composition comprising:
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a single-phase liquid formulation comprising a substantially non-aqueous solvent system suitable for injection, an aqueous acetate buffer, and bortezomib, wherein the bortezomib is present in the formulation at a therapeutically effective concentration; wherein the solvent system comprises as a predominant component propylene glycol, and wherein the buffer has a pH of 3; and wherein the solvent system, the buffer, and the pH are selected such as to be effective to suppress formation of at least one of an amide degradation product, a first carbinolamide degradation product, and a second carbinolamide degradation product when the liquid formulation is stored under storage conditions. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method of suppressing formation of a plurality of degradation products of bortezomib in solution, comprising:
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compounding a single-phase liquid formulation from a substantially non-aqueous solvent system suitable for injection, an aqueous acetate buffer, and bortezomib, wherein the bortezomib is present in the formulation at a pharmaceutically effective concentration; wherein the solvent system comprises as a predominant component propylene glycol and wherein the buffer has a pH of 3; and wherein the solvent system, the buffer, and the pH are selected such as to be effective to suppress formation of at least one of an amide degradation product, a first carbinolamide degradation product, and a second carbinolamide degradation product when the liquid formulation is stored under storage conditions. - View Dependent Claims (12, 13, 14, 15)
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Specification