Peroxide removal from drug delivery vehicle
Inventors
Junnarkar, Gunjan • DesJardin, Michael A. • Carr, John P.
Assignees
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Publication Number
US-11083796-B2
Publication Date
2021-08-10
Expiration Date
Abstract
The present invention is related to methods for lowering peroxide levels in sucrose acetate isobutyrate formulations and to composition used in and formed by such methods.
Core Innovation
The invention relates to peroxide-removal in sucrose acetate isobutyrate (SAIB) drug delivery vehicles. It provides a formulation comprising a drug and SAIB together with peroxide present at a defined level, and uses bisulfite salts to reduce peroxide in the SAIB. The treated SAIB is associated with lower peroxide levels and reduced oxidative impact on the drug-containing formulation.
A peroxide-reduction approach using bisulfite salts is described, including sodium metabisulfite, sodium bisulfite, potassium bisulfite, and potassium metabisulfite salts. The treated SAIB is characterized by substantially reduced peroxide levels, including targets down to less than 20 ppm, preferably less than 10 ppm, and in some cases less than 5 ppm. The document further states peroxide reductions to about less than 5% of starting levels.
The disclosure includes stability study data for omega-interferon in SAIB, comparing untreated SAIB peroxide levels to sodium metabisulfite-treated SAIB with much lower peroxide. The treated formulation is reported to show reduced oxidation, deamidation, and dimerization relative to untreated conditions, with analysis including monomer/dimer assessment and characterization by methods such as SEC and rp-HPLC. The document also states that other peroxide-reduction approaches were nominal or ineffective, while the bisulfite salt approach provides the observed peroxide reduction and associated stability improvements.
The treated SAIB is further described as being used in an osmotically pumped implantable device, including a Duros® device for in vivo drug delivery. The disclosure frames this in the context of drug-eluting uses involving a semipermeable membrane and piston or osmotic pressure driven delivery, where the peroxide-reduced SAIB formulation supports delivery of the drug in the implantable device.
Claims Coverage
The partial claims content includes two independent claims. Across these, the coverage centers on a formulation having sucrose acetate isobutyrate and peroxide at defined ppm levels, with one independent claim further requiring a polymer-free formulation; dependent claims refine peroxide sub-ranges and add or specify formulation ingredients and drug selections.
Peroxide-containing SAIB formulation with 2.6–20 ppm peroxide
A formulation comprising a drug, sucrose acetate isobutyrate, and peroxide, wherein the peroxide is present in the formulation at a level ranging from 2.6 ppm to 20 ppm.
Polymer-free SAIB formulation with 2.6–20 ppm peroxide
A formulation comprising a drug, sucrose acetate isobutyrate, and peroxide, wherein the peroxide is present in the formulation at a level ranging from 2.6 ppm to 20 ppm, and wherein the formulation is polymer-free.
The independent claims define peroxide-containing drug formulations using sucrose acetate isobutyrate with peroxide levels of 2.6 ppm to 20 ppm, and the second independent claim additionally limits the formulation to being polymer-free. Dependent claims further narrow peroxide sub-ranges and specify additional components such as N-methyl pyrrolidone and pharmaceutically acceptable solvents, while also enumerating drug classes including local anesthetics and other categories.
Stated Advantages
Substantially reduced peroxide levels in SAIB formulations, including targets down to less than 20 ppm, preferably less than 10 ppm, and in some cases less than 5 ppm.
Reduced oxidation, deamidation, and dimerization of omega-interferon in SAIB when treated with sodium metabisulfite versus untreated SAIB.
Documented Applications
In vivo drug delivery using a Duros® osmotically pumped implantable device, employing the peroxide-reduced SAIB formulation.
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