Stabilized pentosan polysulfate (pps) formulations and methods of analyzing them
AssigneeNutramax Laboratories, Inc.
InventorsJerry A. Ellinghuysen, Charles Filburn, David Griffin, Todd R. Henderson
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Abstract
Various pentosan polysulfate (PPS) formulations useful for treatment of osteoarthritis, interstitial cystitis, and other conditions of mammals are provided. These formulations showed improved resistance to degradation and discoloration and improved stability at physiological pH, even after sterilization. Capillary electrophoresis analysis of these formulations indicates that various formulations remain stable under conditions that caused degradation of PPS in prior art PPS formulations.
Claims83
A liquid formulation comprising pentosan polysulfate (PPS), wherein the formulation is stable without refrigeration.
A liquid formulation comprising oligosaccharides, wherein the oligosaccharides consist essentially of pentosan polysulfate and wherein the formulation is stable without refrigeration.
A method of detecting a degradation product other than sulfate in a sample of a liquid formulation comprising pentosan polysulfate (PPS), the method comprising:
- terminally sterilizing the sample;
- and
- using capillary electrophoresis to detect in the sample one or more degradation products other than sulfate.
A liquid injectable dosage form comprising pentosan polysulfate (PPS), wherein the dosage form is stable without refrigeration.
An injectable dosage form comprising:
- pentosan polysulfate (PPS) at a concentration of about 250 mg/mL;
- sodium bisulfite at a concentration of up to about 20 mg/mL;
- and EDTA at a concentration of about 0.25 mg/mL;
- wherein the formulation is stable without refrigeration in a pH range of about 6 to about 7.
An injectable dosage form comprising:
- pentosan polysulfate (PPS) at a concentration of about 250 mg/mL;
- sodium bisulfite at a concentration of up to about 10 mg/mL;
- EDTA at a concentration of about 0.25 mg/mL;
- and methyl paraben at a concentration of about 1 mg/mL;
- wherein the formulation is stable without refrigeration in a pH range of about 5.8 to about 6.2.
An injectable dosage form comprising:
- pentosan polysulfate (PPS) in a concentration of about 250 mg/mL;
- sodium bisulfite in a concentration of up to about 10 mg/mL;
- EDTA in a concentration of about 0.25 mg/mL;
- and methyl paraben in a concentration of about 1 mg/mL;
- wherein the formulation is stable without refrigeration in a pH range of about 7.8 to about 8.2.
A method for detecting an indicium of stability of a pentosan polysulfate (PPS) formulation using capillary electrophoresis, comprising:
- preparing a sample of the formulation in a concentration of about 1 to about 5 mg/mL in water;
- preparing an electropherogram for the formulation using capillary electrophoresis in a manner that satisfies a Peak Resolution Standard, the electropherogram comprising a change-in-absorption—versus-time graph;
- identifying a substantially bell-shaped portion of the electropherogram substantially defining a bell and corresponding to PPS, and
- determining the indicium of stability of the formulation based on a size characteristic of the bell in comparison to a size characteristic of the one or more peaks, wherein size characteristics are determined by valley-to-valley integration.
A liquid formulation comprising pentosan polysulfate (PPS), wherein a capillary electrophoresis analysis of the formulation at a sample concentration of about 1 mg/mL to about 5 mg/mL shows a substantially bell-shaped curve corresponding to the presence of PPS in a graph of change-in-absorption-versus-time, the bell-shaped curve comprising a first portion corresponding to an earlier absorption and a second portion corresponding to a later absorption, the first portion and the second portion joined at a middle peak portion, wherein the area inside the substantially bell-shaped portion of the curve is more than about ten times greater than the total area defined by all distinct peaks that appear in the first portion of the substantially bell-shaped curve, wherein area is determined by valley-to-valley integration.
Dependencies are inferred from the claim text.