SUSTAINED-RELEASE OF SALMON-CALCITONIN INVIVO FROM LACTIDE - GLYCOLIDE COPOLYMER DEPOTS

Studies were carried out to determine whether monolithic depot formula tions, prepared using lactide:glycolide copolymers, could be used to a dminister salmon calcitonin (sCT) to rats in vivo. Formulations contai ning 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of p eptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma cal cium concentrations and cumulative weight gain of the animals were use d to measure pharmacological effects of the released sCT. Release of s CT from the depots was controlled by the copolymer and was sustained f or periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading o f the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day pe riod postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between day s 11 and 18. Release of peptide from the depots was essentially comple te by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have ap plication for the convenient clinical administration of sCT in metabol ic bone diseases.