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Title: Formation of stable submicron peptide or protein particles by thin film freezing

The present invention includes compositions and methods for preparing micron-sized or submicron-sized particles by dissolving a water soluble effective ingredient in one or more solvents; spraying or dripping droplets solvent such that the effective ingredient is exposed to a vapor-liquid interface of less than 50, 100, 150, 200, 250, 200, 400 or 500 cm.sup.-1 area/volume to, e.g., increase protein stability; and contacting the droplet with a freezing surface that has a temperature differential of at least C. between the droplet and the surface, wherein the surface freezes the droplet into a thin film with a thickness of less than 500 micrometers and a surface area to volume between 25 to 500 cm.sup.-1.
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Patent Number(s):
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Resource Relation:
Patent File Date: 2015 Jan 22
Research Org:
Board of Regents, The University of Texas System, Austin, TX (United States)
Sponsoring Org:
Country of Publication:
United States

Other works cited in this record:

Injectable Oily Peptide Preparations and Processes for their Manufacture
patent, March 1975

Cosmetic and pharmaceutical vehicle thickened with solid emulsifier
patent, January 1982

Pseudoplastic gel transfer
patent, May 1986

Highly pseudoplastic polymer solutions
patent, June 1986

Droplet freezing method and apparatus
patent, July 1989

Ophthalmological composition of the type which undergoes liquid-gel phase transition
patent, August 1989

Sustained release, comfort formulation for glaucoma therapy
patent, March 1990

Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions
patent, May 1993

Pharmaceutical composition in gel form in a dispensing package
patent, April 1994

Injectable extended release formulations and methods
patent, October 1994

Use of carrageenans in topical ophthalmic compositions
patent, April 1995

Prolonged release of biologically active somatotropin
patent, May 1995

Oral sustained release drug delivery device
patent, April 1996

Viscous suspensions of controlled-release drug particles
patent, July 1996

Erosion rate modifier for use in bioerodible drug delivery devices and method of use
patent, November 1996

Method for identifying an oligonucleotide aptamer specific for a target
patent, December 1996

Methods of producing nucleic acid ligands
patent, January 1997

Method of preparing a drug delivery system comprising a drug and a gel using a syringe
patent, March 1997

Pharmaceutical formulation
patent, June 1997

Systematic evolution of ligands by exponential enrichment: chimeric selex
patent, June 1997

Protein formulation
patent, July 2001

Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle
patent, August 2007

Production of microspheres
patent, May 2008

Nanoclusters for delivery of therapeutics
patent, January 2010

Spherical protein particles and methods for making and using them
patent, August 2011

Low viscosity highly concentrated suspensions
patent, July 2014

Formation of stable submicron peptide or protein particles by thin film freezing
patent, March 2015

Commercial challenges of protein drug delivery
journal, January 2005

Advances in ultrarapid freezing for the preservation of cellular ultrastructure
journal, January 1986
  • Gilkey, John C.; Staehelin, L. Andrew
  • Journal of Electron Microscopy Technique, Vol. 3, Issue 2, p. 177-210
  • DOI: 10.1002/jemt.1060030206

Role of calcium phosphate nanoclusters in the control of calcification
journal, April 2009

Concentrated Dispersions of Equilibrium Protein Nanoclusters That Reversibly Dissociate into Active Monomers
journal, January 2012
  • Johnston, Keith P.; Maynard, Jennifer A.; Truskett, Thomas M.
  • ACS Nano, Vol. 6, Issue 2, p. 1357-1369
  • DOI: 10.1021/nn204166z

Reversible Self-Association of a Concentrated Monoclonal Antibody Solution Mediated by Fab–Fab Interaction That Impacts Solution Viscosity
journal, October 2008
  • Kanai, Sonoko; Liu, Jun; Patapoff, Thomas W.
  • Journal of Pharmaceutical Sciences, Vol. 97, Issue 10, p. 4219-4227
  • DOI: 10.1002/jps.21322

Protein Inhalation Powders: Spray Drying vs Spray Freeze Drying
journal, January 1999
  • Maa, Yuh‐Fun; Nguyen, Phuong‐Anh; Sweeney, Theresa
  • Pharmaceutical Research, Vol. 16, Issue 2, p. 249-254
  • DOI: 10.1023/A:1018828425184

Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs
journal, January 2007
  • Overhoff, Kirk A.; Engstrom, Josh D.; Chen, Bo
  • European Journal of Pharmaceutics and Biopharmaceutics, Vol. 65, Issue 1, p. 57-67
  • DOI: 10.1016/j.ejpb.2006.07.012

Solution-Based Particle Formation of Pharmaceutical Powders by Supercritical or Compressed Fluid Co2 and Cryogenic Spray-Freezing Technologies
journal, January 2001
  • Rogers, True L.; Johnston, Keith P.; Williams, Robert O.
  • Drug Development and Industrial Pharmacy, Vol. 27, Issue 10, p. 1003-1015
  • DOI: 10.1081/DDC-100108363

Spray freezing into liquid versus spray-freeze drying: Influence of atomization on protein aggregation and biological activity
journal, January 2006
  • Yu, Zhongshui; Johnston, Keith P.; Williams, Robert O.
  • European Journal of Pharmaceutical Sciences, Vol. 27, Issue 1, p. 9-18
  • DOI: 10.1016/j.ejps.2005.08.010

Coarse-Grained Strategy for Modeling Protein Stability in Concentrated Solutions
journal, October 2005

Unusual properties of aqueous solutions of l-proline: A molecular dynamics study
journal, November 2005
  • Civera, Monica; Sironi, Maurizio; Fornili, Sandro L.
  • Chemical Physics Letters, Vol. 415, Issue 4-6, p. 274-278
  • DOI: 10.1016/j.cplett.2005.08.145

Vapor Pressure Osmometry Studies of Osmolyte−Protein Interactions:  Implications for the Action of Osmoprotectants in Vivo and for the Interpretation of “Osmotic Stress” Experiments in Vitro
journal, April 2000
  • Courtenay, E. S.; Capp, M. W.; Anderson, C. F.
  • Biochemistry, Vol. 39, Issue 15, p. 4455-4471
  • DOI: 10.1021/bi992887l

Anomalously Large Equilibrium Clusters of Colloids
journal, November 2001
  • Groenewold, Jan; Kegel, Willem K.
  • The Journal of Physical Chemistry B, Vol. 105, Issue 47, p. 11702-11709
  • DOI: 10.1021/jp011646w

Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant
journal, August 2006
  • Ignatova, Z.; Gierasch, L. M.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 36, p. 13357-13361
  • DOI: 10.1073/pnas.0603772103

Enhancement of thermal stability and inhibition of protein aggregation by osmolytic effect of hydroxyproline
journal, January 2007
  • Kar, Karunakar; Kishore, Nand
  • Biopolymers, Vol. 87, Issue 5-6, p. 339-351
  • DOI: 10.1002/bip.20834

Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody
journal, July 2009
  • Miao, Fudu; Velayudhan, Ajoy; DiBella, Elsie
  • Biotechnology Progress, Vol. 25, Issue 4, p. 964-972
  • DOI: 10.1002/btpr.168

Thermophysical Properties of Trehalose and Its Concentrated Aqueous Solutions
journal, January 1997
  • Miller, Danforth P.; de Pablo, Juan J.; Corti, Horacio
  • Pharmaceutical Research, Vol. 14, Issue 5, p. 578-590
  • DOI: 10.1023/A:1012192725996

Phase Behavior of Small Attractive Colloidal Particles
journal, January 1996
  • Rosenbaum, D.; Zamora, P. C.; Zukoski, C. F.
  • Physical Review Letters, Vol. 76, Issue 1, p. 150-153
  • DOI: 10.1103/PhysRevLett.76.150

Coarse-Grained Strategy for Modeling Protein Stability in Concentrated Solutions. II: Phase Behavior
journal, March 2006
  • Shen, Vincent K.; Cheung, Jason K.; Errington, Jeffrey R.
  • Biophysical Journal, Vol. 90, Issue 6, p. 1949-1960
  • DOI: 10.1529/biophysj.105.076497

Challenges in the development of high protein concentration formulations
journal, June 2004
  • Shire, Steven J.; Shahrokh, Zahra; Liu, Jun
  • Journal of Pharmaceutical Sciences, Vol. 93, Issue 6, p. 1390-1402
  • DOI: 10.1002/jps.20079

Protein−solute interactions affect the outcome of ultrafiltration/diafiltration operations
journal, September 2004
  • Stoner, Michael R.; Fischer, Norm; Nixon, Lori
  • Journal of Pharmaceutical Sciences, Vol. 93, Issue 9, p. 2332-2342
  • DOI: 10.1002/jps.20145

Is Random Close Packing of Spheres Well Defined?
journal, March 2000
  • Torquato, S.; Truskett, T. M.; Debenedetti, P. G.
  • Physical Review Letters, Vol. 84, Issue 10, p. 2064-2067
  • DOI: 10.1103/PhysRevLett.84.2064

Molecular Mechanisms of Cryoprotection in Aqueous Proline:  Light Scattering and Molecular Dynamics Simulations
journal, April 2008
  • Troitzsch, R. Z.; Vass, H.; Hossack, W. J.
  • The Journal of Physical Chemistry B, Vol. 112, Issue 14, p. 4290-4297
  • DOI: 10.1021/jp076713m

Enhancement of Protein Crystal Nucleation by Critical Density Fluctuations
journal, September 1997

The thermodynamic mechanism of protein stabilization by trehalose
journal, February 1997

Structure and thermodynamics of colloidal protein cluster formation: Comparison of square-well and simple dipolar models
journal, September 2009
  • Young, Teresa M.; Roberts, Christopher J.
  • The Journal of Chemical Physics, Vol. 131, Issue 12, Article No. 125104
  • DOI: 10.1063/1.3238569

Macromolecular Crowding and Confinement: Biochemical, Biophysical, and Potential Physiological Consequences
journal, June 2008

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