New insights on the burst release kinetics of spray-dried PLGA microspheres

Abstract

Spray drying is one of the leading manufacturing methods for active pharmaceutical ingredients (APIs) owing to its rapid, single-step, and cost-effective nature. It also has the capacity to generate microspheres capable of controlled release of APIs including biomolecules and vaccines. However, one of the key challenges of spray-dried formulations especially with poly(lactic-co-glycolic acid) (PLGA)-based controlled-release injectables is burst release, where a significant fraction of the API is released prematurely within a short period of time following administration, leading to detrimental impact on the performance and quality of end products. This study uses a model API, bovine serum albumin (BSA) protein, to identify the sources of burst release that may affect the kinetics and performance of long-acting injectable microsphere formulations. Spray-dried microspheres with various formulations (i.e., variable BSA/PLGA ratios) were characterized in terms of their morphology, particle size, surface area, thermal properties, moisture content, as well as chemical compositions and their distributions to investigate the impact of spray drying on the burst release phenomenon. The results suggest that a relatively high initial release (85%) observed is mainly attributed to the protein distribution close to the particle surface. Morphology analysis provided evidence that the microspheres retained their spherical structure during the burst release phase. X-ray photoelectron spectroscopy, hard X-ray photoelectron spectroscopy, and argon cluster sputtering-assisted time-of-flight secondary ion mass spectrometry analysis suggest an enrichment of PLGA on particle surfaces with buried BSA protein. The statistically significant difference in particle size and surface area between three different formulations may be responsible for an initial variation in release but did not seem to alter the overall burst release profile. Considering the suggested source of burst release, the two-fluid spray-drying method, characterized by a single liquid feed delivering a preprepared emulsion, generated matrix-type microspheres with a surface layer of PLGA, as evidenced by surface analysis. The PLGA surface layer proved to be prone to degradation and pore formation, allowing for faster diffusion of BSA out of the microspheres, resulting in a burst release. Increasing the polymer concentration did not seem to halt this process.

Publication DOI: https://doi.org/10.1021/acs.molpharmaceut.4c00686
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Aston University (General)
Funding Information: This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and Aston University funded Midlands Integrative Biosciences Training Partnership(MIBTP) (BB/T00746X/1). The analytical work involving XPS, HAXPES, and ToF-SIMS
Additional Information: Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: PLGA microspheres,burst release,chemical depth profiling,spray drying,surface analysis,Molecular Medicine,Pharmaceutical Science,Drug Discovery
Publication ISSN: 1543-8392
Last Modified: 21 Nov 2024 08:23
Date Deposited: 04 Nov 2024 16:50
Full Text Link:
Related URLs: https://pubs.ac ... rmaceut.4c00686 (Publisher URL)
PURE Output Type: Article
Published Date: 2024-10-25
Published Online Date: 2024-10-25
Accepted Date: 2024-10-16
Submitted Date: 2024-06-20
Authors: Michaelides, Kyprianos
Al Tahan, Mohamad Anas
Zhou, Yundong
Trindade, Gustavo F.
Cant, David J.H.
Pei, Yiwen
Dulal, Pawan
Al-Khattawi, Ali (ORCID Profile 0000-0002-2498-2817)

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