TY - JOUR
T1 - Evolution of the microstructure and the drug release upon annealing the drug loaded lipid-surfactant microspheres
AU - Kushwah, Varun
AU - Gomes Lopes, Diogo
AU - Koutsamanis, Ioannis
AU - Plank, Harald
AU - Ardelean, Stefan
AU - Sarkar, Avik
AU - Prpich, Andrew
AU - am Ende, Mary T.
AU - Schmidt, Heather Frericks
AU - Doshi, Pankaj
AU - Shamblin, Sheri
AU - Laggner, Peter
AU - Paudel, Amrit
PY - 2020
Y1 - 2020
N2 - The present study investigates the drug release-governing microstructural properties of melt spray congealed microspheres encapsulating the drug crystals in the matrix of glyceryl behenate and poloxamer (pore former). The solid-state, morphology, and micromeritics of the microspheres were characterized, before and after annealing, using calorimetry, X-ray scattering, porosimetry, scanning electron microscopy, and, NMR diffusometry. The in vitro drug release from and water uptake by the microspheres were obtained. The extent and the rate of drug release from the microspheres increased with a high poloxamer content and at higher annealing temperature and RH. All the drug release profiles were describable using the Higuchi release kinetics pointing towards the diffusion controlled release, both before and after annealing. The annealing process led to the polymorphic conversion of lipid and the increase in the pore size, predominantly at a higher temperature and humidity and for a high poloxamer content. The poloxamer domain increased from an initial 300 nm, up to 2000 nm upon annealing. The water diffusion rate inside the annealed microsphere was twice as fast as for unannealed counterparts. The findings relate the overall phase and pore structure change of the microsphere to the increased drug release induced by annealing. This work serves as a basis for the rational understanding of the modification of the in vitro performance by annealing, a widely used post-process for solid lipid products.
AB - The present study investigates the drug release-governing microstructural properties of melt spray congealed microspheres encapsulating the drug crystals in the matrix of glyceryl behenate and poloxamer (pore former). The solid-state, morphology, and micromeritics of the microspheres were characterized, before and after annealing, using calorimetry, X-ray scattering, porosimetry, scanning electron microscopy, and, NMR diffusometry. The in vitro drug release from and water uptake by the microspheres were obtained. The extent and the rate of drug release from the microspheres increased with a high poloxamer content and at higher annealing temperature and RH. All the drug release profiles were describable using the Higuchi release kinetics pointing towards the diffusion controlled release, both before and after annealing. The annealing process led to the polymorphic conversion of lipid and the increase in the pore size, predominantly at a higher temperature and humidity and for a high poloxamer content. The poloxamer domain increased from an initial 300 nm, up to 2000 nm upon annealing. The water diffusion rate inside the annealed microsphere was twice as fast as for unannealed counterparts. The findings relate the overall phase and pore structure change of the microsphere to the increased drug release induced by annealing. This work serves as a basis for the rational understanding of the modification of the in vitro performance by annealing, a widely used post-process for solid lipid products.
KW - Annealing
KW - Diffusometry
KW - Lipid polymorphism
KW - Microsphere
KW - Microstructure
UR - http://www.scopus.com/inward/record.url?scp=85081264441&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejps.2020.105278
DO - https://doi.org/10.1016/j.ejps.2020.105278
M3 - Article
SN - 0928-0987
VL - 147
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 105278
ER -