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Publication Number
US-9949922-B2
Publication Date
2018-04-24
Expiration Date
Abstract
This invention relates to a silica hydrogel composite obtainable by mixing silica particles, comprising an encapsulated agent, with a silica sol, wherein obtained hydrogel composite is shear-thinning. The present invention also relates to use of the silica hydrogel composite according to the invention for an injectable, flowing or extrudable formulation. The present invention further relates to a method for preparing the silica hydrogel.
Core Innovation
The invention relates to a silica hydrogel composite obtained by mixing silica microparticles with a silica sol, where the silica microparticles comprise an encapsulated agent other than the silica itself and have a diameter between 1 µm and 300 µm. The silica sol comprises solid particles having a size of 50 nm or less, and the silica sol has a solid content of 5 wt-% or less. The composite comprises up to 85 wt-% of the silica microparticles and is shear-thinning.
The composite is characterized by rheology in which the hydrogel behavior is associated with shear-thinning, and the formulation is intended to be an injectable or extrudable formulation. The transition to hydrogel formation is described as unexpectedly greatly reducing initial burst release while largely preserving later overall release kinetics.
The disclosure further grounds the composite in a defined microstructure and mechanical behavior, using rheological parameters such as storage modulus, loss modulus, and elastic modulus, where gel-like behavior is associated with G′ greater than G″ and an elastic modulus measured in the linear viscoelastic region can be below 300 kPa. The encapsulated agents include nimodipine and fluorescein, and the composite is compared to silica gels, chitosan hydrogels, and silica–organogel systems.
Claims Coverage
The document includes two independent claims. Together they cover a composition defined by silica microparticles and silica sol with shear-thinning behavior, and a method for preparing that composite by mixing the same defined components.
Silica hydrogel composite with shear-thinning silica sol and microparticles
A silica hydrogel composite obtained by mixing silica microparticles comprising an encapsulated agent other than the silica itself and having a diameter between 1 µm and 300 µm with a silica sol comprising solid particles ≤50 nm, wherein the silica sol has a solid content ≤5 wt-%, the silica hydrogel composite comprises up to 85 wt-% of the silica microparticles, and the hydrogel composite is shear-thinning.
Method for preparing a shear-thinning silica hydrogel composite
A method for preparing a silica hydrogel composite comprising mixing silica microparticles comprising a biologically active agent other than the silica itself and having a diameter between 1 µm and 300 µm with a silica sol, wherein the silica sol has a solid content ≤5 wt-% and comprises solid particles ≤50 nm, the hydrogel composite comprises up to 85 wt-% of the silica microparticles, and the hydrogel composite is shear-thinning.
The claimed scope is anchored on a silica hydrogel composite formed by mixing defined-size silica microparticles carrying a non-silica agent with a defined-size silica sol, constrained by sol solid content and microparticle fraction, and producing a shear-thinning hydrogel composite; a corresponding preparation method by mixing the same components is also claimed.
Stated Advantages
Unexpectedly greatly reduces initial burst release.
Largely preserves later overall release kinetics.
Documented Applications
Drug delivery using a shear-thinning/injectable silica microparticle–silica sol hydrogel composite.
Parenteral administration routes are explicitly enumerated in dependent claim language, including intravenous, subcutaneous, intramuscular, and intraocular.
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