Modulating the Pore Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration

Abstract

Spray freeze drying (SFD) is an ice templating method used to produce highly porous particles with complex pore architectures governed by ice nucleation and growth. SFD particles have been advanced as drug carrier systems, but the quantitative description of the morphology formation in the SFD process is still challenging. Here, the pore space dimensions of SFD particles prepared from aqueous dextran solutions of varying molecular weights (40–200 kDa) and concentrations (5–20%) are analyzed using scanning electron microscopy. Coexisting morphologies composed of cellular and dendritic motifs are obtained, which are attributed to variations in the ice growth mechanism determined by the SFD system and modulation of these mechanisms by given precursor solution properties leading to changes in their pore dimensions. Particles with low-aspect ratio cellular pores showing variation of around 0.5–1 μm in diameter with precursor composition but roughly constant with particle diameter are ascribed to a rapid growth regime with high nucleation site density. Image analysis suggests that the pore volume decreases with dextran solid content. Dendritic pores (≈2−20 μm in diameter) with often a central cellular region are identified with surface nucleation and growth followed by a slower growth regime, leading to the overall dendrite surface area scaling approximately linearly with the particle diameter. The dendrite lamellar spacing depends on the concentration according to an inverse power law but is not significantly influenced by molecular weight. Particles with highly elongated cellular pores without lamellar formation show intermediate pore dimensions between the above two limiting morphological types. Analysis of variance and post hoc tests indicate that dextran concentration is the most significant factor in affecting the pore dimensions. The SFD dextran particles herein described could find use in pulmonary drug delivery due to their high porosity and biocompatibility of the matrix material.

Spray freeze dried niclosamide nanocrystals embedded dry powder for high dose pulmonary delivery

“…3 d3), cellular pore structure was found on the surface of SF −80 D-N 20 D 2 T 1 microparticles ( Fig. 3 h3), possible ascribing to the rapid growth regime with high nucleation site density [ 45 ]. Surprisingly, such phenomenon was not observed in those samples containing Leu ( Fig.…”

Tailored Sugar-Mediated Porous Particle Structures for Improved Dispersion of Drug Nanoparticles in Spray-Freeze-Drying

“…12,13 This approach uses ice as a template to craft porous particles and offers versatility, enabling not only the fabrication of basic porous materials but also, under specific conditions, the morphological engineering of particles with intricate pore architectures. 14 Furthermore, using ice as a template is an environmentally friendly manufacturing process for bioproducts, circumventing the need for alkaline or organic solvents. Because SFD can mitigate thermal stress, it is also an efficient method for handling heat-sensitive proteins and pharmaceuticals.…”

“…Further, they successfully regulated the release rate of indomethacin from a porous pectin fabricated using the same method . Spray-freeze-drying (SFD) has garnered attention as an innovative particle engineering method blending traditional freeze-drying with heated assisted spray-drying, especially useful to food and pharmaceuticals. , This approach uses ice as a template to craft porous particles and offers versatility, enabling not only the fabrication of basic porous materials but also, under specific conditions, the morphological engineering of particles with intricate pore architectures . Furthermore, using ice as a template is an environmentally friendly manufacturing process for bioproducts, circumventing the need for alkaline or organic solvents.…”