TY - JOUR
T1 - The mechanism behind the biphasic pulsatile drug release from physically mixed poly(DL-lactic(-co-glycolic) acid)-based compacts
AU - Beugeling, Max
AU - Grasmeijer, Niels
AU - Born, Philip A.
AU - van der Meulen, Merel
AU - van der Kooij, Renée S.
AU - Schwengle, Kevin
AU - Baert, Lieven
AU - Amssoms, Katie
AU - Frijlink, Henderik W.
AU - Hinrichs, Wouter L. J.
N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - Successful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees' comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(DL-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous flow of the polymer and further release was inhibited. After a certain period of time, the polymer matrix ruptured, possibly due to a build-up in osmotic pressure, resulting in a pulsatile release of the remaining amount of drug. The compression force and the molecular weight of the incorporated drug did not influence the release profile. Understanding this mechanism could contribute to further develop single-injection vaccines.
AB - Successful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees' comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(DL-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous flow of the polymer and further release was inhibited. After a certain period of time, the polymer matrix ruptured, possibly due to a build-up in osmotic pressure, resulting in a pulsatile release of the remaining amount of drug. The compression force and the molecular weight of the incorporated drug did not influence the release profile. Understanding this mechanism could contribute to further develop single-injection vaccines.
KW - Biphasic pulsatile release
KW - Compaction
KW - Controlled release
KW - Glass transition temperature
KW - Poly(DL-lactic(-co-glycolic) acid)
KW - Single-injection vaccine
KW - INITIAL BURST RELEASE
KW - POLY(LACTIDE-CO-GLYCOLIDE) IMPLANTS
KW - PROTEIN INSTABILITY
KW - DELIVERY-SYSTEMS
KW - PLGA
KW - MICROSPHERES
KW - DEGRADATION
KW - TABLETS
KW - MODEL
KW - MICROPARTICLES
U2 - 10.1016/j.ijpharm.2018.09.025
DO - 10.1016/j.ijpharm.2018.09.025
M3 - Article
C2 - 30223077
SN - 0378-5173
VL - 551
SP - 195
EP - 202
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -