Long-term stability and in vitro release of hPTH(1-34) from a multi-reservoir array.

Purpose: 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.