title: Long-term stability and in vitro release of hPTH(1-34) from a multi-reservoir array.
abstract: OBJECTIVE
  Therapeutic peptides generally exhibit poor oral bioavailability and require alternative methods of delivery. Implanted microelectromechanical systems-based multi-reservoir devices enable programmable, chronic, pulsatile peptide delivery. This report describes parathyroid hormone fragment (hPTH (1-34)) formulations suitable for delivery from a multi-reservoir array.
  
  
  METHODS
  The stability of hPTH(1-34) lyophilizates obtained from aqueous acidic solutions was assessed by reverse phase high pressure liquid chromatography. An in vitro test device measured in vitro release kinetics.
  
  
  RESULTS
  Novel, highly concentrated (>50 mg/mL) hPTH(1-34) solutions were dispensed as bulk samples (1-3 mg peptide) in vials and as individual doses (13-21 microg peptide) in reservoir arrays. Bulk and array samples were lyophilized and stored at 37 degrees C. Bulk lyophilizate hPTH(1-34) purity after lyophilization, after 8 weeks, and after 26 weeks exceeded 96%, 90%, and 80%, respectively. The hPTH(1-34) stored in multi-reservoir arrays exhibited similar purity over 29 weeks at 37 degrees C. Initially and over 29 weeks, over half of the peptide was consistently released from arrays into neutral, isotonic solution in less than 30 min with quantitative recoveries (>95%) within 3 h.
  
  
  CONCLUSIONS
  Clinically relevant formulations of hPTH(1-34) for use with implantable multi-reservoir devices are achievable.
authors.affiliation: MicroCHIPS, Inc., 6-B Preston Court, Bedford, Massachusetts 01730, USA. eproos@mchips.com
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Proos
authors.forename: James H
authors.initials: JH
authors.lastname: Prescott
authors.forename: Mark A
authors.initials: MA
authors.lastname: Staples
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005612:Freeze Drying; D006801:Humans; D013058:Mass Spectrometry; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility
chemical_list: D010281:Parathyroid Hormone