Determination of the Binding Constant for the Molecular Inclusion Complex Between Alprostadil and Alpha-Cyclodextrin by means of 1. Conuctometry and 2. Microcalorimetry
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The binding, or stability constant between alprostadil (PGE1) and a-cyclodextrin was determined by conductometry and isothermal titration calorimetry. Alpha-cyclodextrin is an excipient material in Caverject Dual Chamber Syringe (DCS) added to enhance stability. The binding constant is used to calculate the amount ofPGE1 free upon reconstitution. The project's goal is to substitute in vivo with in vitro testing and avoid a pharmacodynamic/clinical efficacy study. In conductometry the electrolysis cell was initially charged with a prepared lithium salt of alprostadil (Li+PGE1-) and titrated with a solution of a-cyclodextrin and a change in specific conductivity is recorded. Similarly, in isothermal titration calorimetry (microcalorimetry) a known volume of alprostadil is loaded into a sample cell in a thermal activity monitor and is titrated with a-cyclodextrin and a change in heat is recorded. In both cases a binding isotherm is generated from which the stability constant is extracted via nonlinear regression analysis. Previously, analogous measurements were made by NMR and capillary electrophoresis (CE).