Research And Development Of A Biodegradable Silica-Silica Composite For Controlled Drug Delivery
Kuuliala, Maija (2018)
2018
Materiaalitekniikka
Teknisten tieteiden tiedekunta - Faculty of Engineering Sciences
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Hyväksymispäivämäärä
2018-03-07
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201802201273
https://urn.fi/URN:NBN:fi:tty-201802201273
Tiivistelmä
The mandator of this study was DelSiTech Ltd, whose silica-silica composite is suitable for parenteral delivery of pharmaceuticals and viral vectors. The goal of this study was to examine low microparticle mass concentrations in the silica-silica composite (Cmp < 0.5 g/ml), for delivering small doses. As the microparticle concentration was reduced, also the R-value of the hydrogel (water to silica alkoxide ratio) was lowered in order to improve the mechanical properties of the hydrogel matrix. A successful formulation was defined with three criteria: 1) the composite is homogeneous with no visible phase separation of hydrogel and microparticles occurring, 2) injectable through 27-G-needle and 3) it should maintain its viscoelastic properties for at least three months. Evaluation as a function of time was of great importance since continuous condensation reaction may go on in the composite for several months and thus alter the composite structure and injectability.
The study consisted of preparation of hydrogels with low R-values and preparation of composites with several formulations and two alternative preparation methods. Properties of the composites were evaluated visually and with 14 days storage test. Shelf-life studies included evaluation of viscoelastic properties with oscillatory measurements and injectability with injection force studies as a function of time for three months at +37°C.
Low R-value was observed to increase structural changes in the composite and hydrogel within time. Low R-value did not compensate the lack of microparticles to obtain a homogeneous formulation. Most of the studied formulations were heterogeneous and sedimentation of microparticles often occurred. One homogeneous formulation, R150 Cmp=0.3 g/ml could be prepared. However, oscillatory measurements and visual observation showed structural changes within time. In addition, injectability was poor which indicated phase separation and heterogeneity of the samples. Thus, a homogeneous formulation could not be prepared. Suggested methods to obtain low microparticle concentrations are addition of the microparticles to a gel or additives to the hydrogels matrix.
The study consisted of preparation of hydrogels with low R-values and preparation of composites with several formulations and two alternative preparation methods. Properties of the composites were evaluated visually and with 14 days storage test. Shelf-life studies included evaluation of viscoelastic properties with oscillatory measurements and injectability with injection force studies as a function of time for three months at +37°C.
Low R-value was observed to increase structural changes in the composite and hydrogel within time. Low R-value did not compensate the lack of microparticles to obtain a homogeneous formulation. Most of the studied formulations were heterogeneous and sedimentation of microparticles often occurred. One homogeneous formulation, R150 Cmp=0.3 g/ml could be prepared. However, oscillatory measurements and visual observation showed structural changes within time. In addition, injectability was poor which indicated phase separation and heterogeneity of the samples. Thus, a homogeneous formulation could not be prepared. Suggested methods to obtain low microparticle concentrations are addition of the microparticles to a gel or additives to the hydrogels matrix.