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Microprecipitation of nanoparticulate pharmaceutical agents using surface active material derived from similar pharmaceutical agents

Patent 5716642 Issued on February 10, 1998. Estimated Expiration Date: Icon_subject February 10, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Patent References

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Crystallized carbohydrate matrix for biologically active substances, a process of preparing said matrix, and the use thereof
Patent #: 4713249
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Inventor: Schroder

Microdroplets of water-insoluble drugs and injectable formulations containing same
Patent #: 4725442
Issued on: 02/16/1988
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Method for making uniformly sized particles from water-insoluble organic compounds
Patent #: 4826689
Issued on: 05/02/1989
Inventor: Violanto

5118528

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Inventors

Application

No. 370928 filed on 01/10/1995

US Classes:

424/489, Particulate form (e.g., powders, granules, beads, microcapsules, and pellets)424/9.1, IN VIVO DIAGNOSIS OR IN VIVO TESTING424/9.4, X-ray contrast imaging agent (e.g., computed tomography, angiography, etc.)424/490Coated (e.g., microcapsules)

Examiners

Primary: Page, Thurman K.
Assistant: Benston, William E. Jr.

Attorney, Agent or Firm

International Class

A61K 009/14

Abstract

This invention describes the preparation of nanoparticulate pharmaceutical agent dispersion via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of suitable surface-modifying, surface-active agents to form a fine particle dispersion of the said pharmaceutical agent. A combination of surface active surface modifying agents comprising a nonionic surface active substance and an anionic surface active material having a chemical structure which is at least on a molecular basis 75% similar to the pharmaceutical agent is used. This process is preferably followed by steps of diafiltration clean-up of the dispersion and then concentration of it to a desired level. This process of dispersion preparation leads to microcrystalline particles of Z-average diameters smaller than 400 nm as measured by photon correlation spectroscopy. Various modifications of precipitation schemes are described, many of which are suitable for large-scale manufacture of these agent dispersions.

Other References

  • Radiology, Jan. 1982, vol. 142, pp. 115-118
  • Lachman, et al, "The Theory and Practice of Industrial Pharmacy", Chapter 2, Milling, p. 45, (1986)
  • Handbook of Experimental Pharmacology, vol. 73, pp. 56-73, 1984
  • Investigative Radiology, vol. 29, Jul.-Aug. 1994
  • International Journal of Pharmaceutics, 52(1989) 101-10
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