Production of Lysozyme-PLGA-Loaded Microparticles for Controlled Release Using Hot-Melt Extrusion
| Autor: | Cláudia Moura, Maria Diná Afonso, João Henriques, Susana Farinha |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Vinyl alcohol
Drug Compounding Pharmaceutical Science 02 engineering and technology Polyethylene glycol Aquatic Science 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Polylactic Acid-Polyglycolic Acid Copolymer Drug Discovery Ecology Evolution Behavior and Systematics PEG 400 Chromatography Ecology Hot Melt Extrusion Technology General Medicine 021001 nanoscience & nanotechnology Controlled release PLGA chemistry Delayed-Action Preparations Drug delivery Solvents Nanoparticles Emulsions Muramidase Extrusion Lysozyme 0210 nano-technology Agronomy and Crop Science |
| Zdroj: | AAPS PharmSciTech. 21 |
| ISSN: | 1530-9932 |
| DOI: | 10.1208/s12249-020-01816-8 |
| Popis: | Biopharmaceuticals are usually administered intravenously with frequent dosing regimens which may decrease patient compliance. Controlled-release formulations allow to reduce the frequency of injections while providing a constant dosing of the biopharmaceutical over extended periods. These formulations are typically produced by emulsions, requiring high amounts of organic solvents and have limited productivity. Hot-melt extrusion (HME) is an alternative technology to produce controlled drug delivery systems. It is a continuous solvent-free process, leading to a small ecological footprint and higher productivity. However, it may induce thermolabile compounds' degradation. In this work, the impact of the formulation and extrusion temperature on lysozyme's bioactivity and release profile of poly(lactic-co-glycolic acid) (PLGA)-based extended release formulations were evaluated using a design-of-experiments (DoE) approach. The lysozyme-loaded PLGA microparticles were produced by HME followed by milling. It was observed 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 temperature 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 alcohol) (PVA) aqueous solution eliminated it. In conclusion, HME is demonstrated to be suitable in producing controlled-release microparticles of small biopharmaceuticals. Graphical abstract. |
| Databáze: | OpenAIRE |
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