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Reviews

Analysis of initial burst in PLGA microparticles

, PhD
Pages 615-628 | Published online: 05 Jun 2008
 

Abstract

Background: This review addresses recent advances in the understanding of the mechanisms that underlie burst release and strategies developed to control burst from poly(lactide-co-glycolide) (PLGA) microparticle formulations. While the initial burst release of drug is not always detrimental, excessive drug release in the burst phase may be toxic, and irregularity in the amount of drug released (e.g., from batch to batch) is not acceptable. Many drugs that are good candidates for sustained release treatments are not miscible in PLGA and common microparticle processing solvents, and, as a result, suffer from excessive initial burst release. Objective: The aim of this review is to provide an update on research to understand the mechanisms that underlie burst release of drugs from PLGA microparticles, and strategies developed to control burst. Methods: This review focuses on literature published since 2004. Results: Strategies to control burst release fall into two general categories. First are efforts to improve the miscibility of drug and polymer by altering the composition of the formulation, for example by altering the salt form of the drug. Secondly, processing methods may be altered (increasing the rate of solvent removal, for example) to prevent drug–polymer separation. The goal of most strategies is to reduce or eliminate burst release, so that the encapsulated drug may be maximally retained in the delivery system for long-term delivery.

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