Biodegradable hollow fibres for the controlled release of hormones

Abstract

Poly( l- lactide), (PLLA), hollow fibres were prepared using a dry-wet phase inversion spinning process. The effect of several spinning parameters (i.e. bore medium flow rate, spinning dope extrusion rate, fibre take-up rate, and spinning height) on the hollow fibre dimensions is reported. The use of several spinning systems (i.e. different solvent/non-solvent pairs with or without additive) resulted in PLLA hollow fibres with varying asymmetric membrane structures, i.e. a porous matrix covered by an internal and external skin varying from very thick and dense to very thin and porous. Some of the differences in membrane structure were qualitatively explained on the basis of a model developed by Reuvers [52] for the formation of flat-sheet membranes by immersion precipitation. Release experiments were carried out using PLLA hollow fibres filled with a 25 wt.% dispersion of micronized 3H-levonorgestrel in castor oil, and a receiving fluid consisting of 40 wt.% aqueous ethanol. The hollow fibre levonorgestrel release rates were found to be dependent on the membrane structure of the hollow fibre wall. For the different hollow fibre samples, zero-order levonorgestrel release rates were found, in the range of 0.1–10 μg/cm/day. Possible release mechanisms are discussed. Preliminary in vivo (rabbit) release experiments showed that constant levonorgestrel blood plasma levels could be obtained for a period up to 210 days. It is concluded that the new biodegradable hollow fibre reservoir device shows very promising properties for possible application as a long-acting contraceptive delivery system.