Stable bortezomib formulations
AssigneeInnoPharma, Inc.
InventorsKumaresh Soppimath, Satish Pejaver, Kanaiyalal R. Patel, Lakkaraju Dasaradhi, Rama Sodum, Hari Desu, Navneet Puri
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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.
Claims15
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.
A method of suppressing formation of a plurality of degradation products of bortezomib in solution, comprising:
- 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.
Dependencies are inferred from the claim text.