Pharmaceutical-grade ferric organic compounds, uses thereof and methods of making same

Abstract

The present invention discloses pharmaceutical-grade ferric organic compounds, including ferric citrate, which are soluble over a wider range of pH, and which have a large active surface area. A manufacturing and quality control process for making a pharmaceutical-grade ferric citrate that consistently complies with the established Manufacture Release Specification is also disclosed. The pharmaceutical-grade ferric organic compounds are suitable for treating disorders characterized by elevated serum phosphate levels.

Description

[0001]This application is a Continuation of U.S. Ser. No. 16 / 832,101, filed Mar. 27, 2020, which is a Continuation of U.S. Ser. No. 16 / 352,455, filed Mar. 13, 2019, which is a Continuation of U.S. Ser. No. 15 / 699,025, filed Sep. 8, 2017, which is a Continuation of U.S. Ser. No. 14 / 701,933, filed May 1, 2015, which is a Continuation of U.S. Ser. No. 14 / 306,756, filed Jun. 17, 2014, which is a Continuation of U.S. Ser. No. 13 / 661,558, filed Oct. 26, 2012, which is a Continuation of U.S. Ser. No. 13 / 289,048, filed Nov. 4, 2011, which is a Continuation of U.S. Ser. No. 12 / 064,058, filed Feb. 18, 2008, which is a National Stage of International Application No. PCT / US2006 / 032385, filed Aug. 18, 2006, which claims the benefit of U.S. Ser. No. 60 / 709,511, filed Aug. 19, 2005, and is a Continuation-in-part of U.S. Ser. No. 11 / 206,981, filed Aug. 18, 2005, which is a Continuation-in-part of International Application No. PCT / US2004 / 004646, filed Feb. 18, 2004, which claims the benefit of U.S. ...

AI Technical Summary

Benefits of technology

[0009]An embodiment of the invention provides a manufacturing and quality control process / analysis for making a pharmaceutical-grade ferric citrate that consistently complies with the established Manufacture Release Specification. The process of the present invention can be adapted to produce multi-kilogram batches of pharmaceutical-grade ferric citrate, and can be readily scaled up to provide additional manufacturing capacity for ferric citrate.

[0063]An additional embodiment is a method for using the pharmaceutical composition to inhibit or even reverse soft tissue mineralization, specifically calcification. Hyperphosphatemia may lead to increased calcium phosphate deposition in hard and soft tissues by increasing the likelihood of binding with free calcium to form insoluble calcium phosphate. Therefore, an effective dose of a composition comprising pharmaceutical-grade ferric citrate may decrease serum phosphate levels and result in a corresponding decrease in calcium phosphate deposition.

[0067]The compositions encompassing pharmaceutical grade ferric citrate may operate according to more than one mechanism. A plausible non-limiting mechanism of action may result from the ferric ion binding phosphate in the GI tract, thus forming an insoluble ferric phosphate precipitate. This, in turn, may result in decrease the uptake of phosphate and phosphate-containing compounds from the GI tract.

[0073]The compositions encompassing pharmaceutical grade ferric citrate may be administered for varying periods of time. In some embodiments, the tolerability of the compositions encompassing pharmaceutical grade ferric citrate allows for long term administration when necessary.

Problems solved by technology

However, commercially scalable manufacturing processes with quality control / analysis measures to ensure and / or to verify the compliance of the pharmaceutical-grade ferric citrate or ferric organic compounds with established standards or specifications were not previously disclosed.

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