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Pharmaceutical Research

, Volume 22, Issue 9, pp 1461–1470 | Cite as

Novel Long-Acting Crystal Formulation of Human Growth Hormone

  • Chandrika Govardhan
  • Nazer Khalaf
  • Chu W. Jung
  • Ben Simeone
  • Amy Higbie
  • Susan Qu
  • Letha Chemmalil
  • Sergey Pechenov
  • Sujit K. Basu
  • Alexey L. Margolin
Research Paper

Purpose

The aim of the study is to solve a significant challenge of extending the half-life of therapeutic proteins using crystalline biopharmaceuticals and without redesigning the molecules.

Methods

Crystals of recombinant human growth hormone were coated with a monomolecular layer of positively charged poly(arginine). The pharmacokinetics and pharmacodynamics of this poly(arginine)-coated human growth hormone crystalline formulation were determined in hypophysectomized rats and monkeys.

Results

Here we have demonstrated for the first time that crystals of human growth hormone coated with positively charged poly(arginine) allowed for in vivo pharmacokinetic release profiles of over several days in animal models. The efficacy of this crystalline formulation injected subcutaneously once a week was found to be equivalent to seven daily soluble injections in the standard weight gain assay using the hypophysectomized rat model and in measurement of serum insulin-like growth factor in monkeys. The nonviscous nature of the suspension facilitated easy administration through a fine, 30-gauge needle and should provide for improved patient convenience and compliance.

Conclusions

The approach described here offers an exciting possibility of being broadly applicable to other therapeutic proteins.

Key Words

crystalline hGH formulation human growth hormone insulin-like growth factor-1 poly(arginine) adsorption sustained release syringeability 

Abbreviations

μE

electrophoretic mobility

ζ

Zeta potential

σ

surface charge density

C

Coulomb

SC

subcutaneous

PK

pharmacokinetic

PD

pharmacodynamic

IGF-1

insulin-like growth factor 1

Notes

Acknowledgments

The authors would like to thank R. Patel for technical assistance and D. Miller and R. Forrest for their assistance in writing this paper.

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Chandrika Govardhan
    • 1
  • Nazer Khalaf
    • 1
  • Chu W. Jung
    • 1
  • Ben Simeone
    • 1
  • Amy Higbie
    • 1
  • Susan Qu
    • 1
  • Letha Chemmalil
    • 1
  • Sergey Pechenov
    • 1
  • Sujit K. Basu
    • 1
  • Alexey L. Margolin
    • 1
  1. 1.Altus Pharmaceuticals Inc.CambridgeUSA

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