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Abstract: Biopharmaceuticals are usually administered i.v. with frequent dosing regimens which may decrease patient compliance.ÌýControlled-​release formulations allow to reduce the frequency of injections while providing a const. dosing of the biopharmaceutical over extended periods.ÌýThese formulations are typically produced by emulsions, requiring high amts. of org. solvents and have limited productivity.ÌýHot-​melt extrusion (HME) is an alternative technol. to produce controlled drug delivery systems.ÌýIt is a continuous solvent-​free process, leading to a small ecol. footprint and higher productivity.ÌýHowever, it may induce thermolabile compds.' degrdn.ÌýIn this work, the impact of the formulation and extrusion temp. on lysozyme' s bioactivity and release profile of poly(lactic-​co-​glycolic acid) (PLGA)​-​based extended release formulations were evaluated using a design-​of-​expts. (DoE) approach.ÌýThe lysozyme-​loaded PLGA microparticles were produced by HME followed by milling.ÌýIt was obsd. that the in vitro release (IVR) profile was mainly affected by the drug load; higher drug load led to higher burst and total lysozyme release after 14 days.ÌýHME temp. seemed to decrease lysozyme' s activity although this correlation was not statistically significant (p value = 0.0490)​.ÌýAdding polyethylene glycol 400 (PEG 400) as a plasticizer to the formulation had no significant impact on the lysozyme release profile.ÌýThe burst release was effectively mitigated with the inclusion of a washing step.ÌýWashing the microparticles with water reduced the burst release by 80​% whereas washing them with a poly(vinyl alc.) (PVA) aq. soln. eliminated it.ÌýIn conclusion, HME is demonstrated to be suitable in producing controlled-​release microparticles of small biopharmaceuticals.

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