Purity and stability assessment of a semi-solid poly(ortho ester) used in drug delivery systems.

The research work carried out for developing bioerodible drug delivery devices in which the erosion process was to be confined to the polymer-water interface is at the origin of the discovery of a class of polymers known as poly(ortho esters) (POEs). Thus far, three POE systems have been described. The latest POE was prepared by a transesterification reaction between a triol and an ortho ester, followed by a self-condensation of the reaction product. This polymer, which exhibits viscous characteristics at room temperature, was investigated for use as a drug delivery system in glaucoma filtering surgery. The assessment of POE purity and stability was carried out by a detailed analysis of the influence of the purification procedure and storage conditions. This bioerodible semi-solid POE was purified by a repeated precipitation procedure. Elimination of the small molecular weight oligomers and monomers and of the catalysts and stabilizers used in the synthesis, as well as a decrease of the polydispersity, were obtained with this method. Fourier transform infrared analysis also verified the disappearance of degradation products after the first precipitation. Drying of the precipitated polymer was performed at 40 degrees C in order to avoid thermal degradation of the POE at higher temperatures and to facilitate solvent evaporation through the polymer network by a reduction of polymer viscosity. Water vapour uptake of the polymers stored at different relative humidities has demonstrated the high moisture sensitivity of these semi-solid POEs. The average molecular weight of the polymer and hence its viscosity, as well as the solubility characteristics of the incorporated drug, were found to have a considerable influence on the rate of water vapour absorption and on polymer degradation. The use of inert gas or vacuum to maintain the polymer under anhydrous conditions has been studied. Storage of the semi-solid POE under argon in sealed glass bottles provides good protection of the polymer over time.