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Article / Oct 06, 2020

Production of Lysozyme-PLGA-Loaded Microparticles for Controlled Release Using Hot-Melt Extrusion

  • Susana Farinha
  • Claudia Moura
  • Maria Dina Afonso
  • João Henriques
AAPS PharmSciTech (2020), 21(7), 274

Abstract: Biopharmaceuticals are usually administered i.v. with frequent dosing regimens which may decrease patient compliance. Controlled-​release formulations allow to reduce the frequency of injections while providing a const. dosing of the biopharmaceutical over extended periods. These formulations are typically produced by emulsions, requiring high amts. of org. solvents and have limited productivity. Hot-​melt extrusion (HME) is an alternative technol. to produce controlled drug delivery systems. It is a continuous solvent-​free process, leading to a small ecol. footprint and higher productivity. However, it may induce thermolabile compds.' degrdn. In 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. The lysozyme-​loaded PLGA microparticles were produced by HME followed by milling. It 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. HME temp. seemed to decrease lysozyme' s activity although this correlation was not statistically significant (p value = 0.0490)​. Adding polyethylene glycol 400 (PEG 400) as a plasticizer to the formulation had no significant impact on the lysozyme release profile. The burst release was effectively mitigated with the inclusion of a washing step. Washing the microparticles with water reduced the burst release by 80​% whereas washing them with a poly(vinyl alc.) (PVA) aq. soln. eliminated it. In conclusion, HME is demonstrated to be suitable in producing controlled-​release microparticles of small biopharmaceuticals.


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