Mechanisms controlling protein release from lipidic implants: Effects of PEG addition

Abstract

Different types of tristearin-based implants for controlled rh-interferon α-2a (IFN-α) release were prepared by compression and thoroughly characterised in vitro. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was added as a co-lyophilisation agent for protein stabilisation and different amounts of polyethylene glycol (PEG) as efficient protein release modifier. To get deeper insight into the underlying mass transport mechanisms, the release of IFN-α, HP-β-CD and PEG into phosphate buffer pH 7.4 was monitored simultaneously and appropriate analytical solutions of Fick's second law of diffusion were fitted to the experimental results. Importantly, the addition of only 5–20% PEG to the lipidic implants significantly altered the resulting protein release rates and the relative importance of the underlying mass transport mechanisms. The release of IFN-α from PEG-free implants was purely diffusion controlled. In contrast, in PEG-containing devices other phenomena were also involved in the control of protein release: the IFN-α release rate remained about constant over prolonged periods of time and the total amounts of mobile IFN-α increased. Interestingly, the release of PEG itself as well as of HP-β-CD from the implants remained purely diffusion controlled, irrespective of the amount of added PEG. Thus, different mass transport mechanisms govern the release of the drug, co-lyophilisation agent and release modifier out of the lipidic implants.