This preclinical study evaluated feasibility of an injectable biodegradable silica hydrogel depot formulation for subconjunctival drug delivery into the eye utilizing dexamethasone as active component. The silica hydrogel formulation was manufactured using spray-dried silica microparticles with encapsulated dexamethasone which were mixed with a silica hydrogel to form a continuous solid phase within an aqueous liquid phase. The formulation was then analyzed for dexamethasone and silica contents, rheology, injectability, as well as in vitro dissolution of dexamethasone and silica. Finally, the formulation was studied for pharmacokinetics and release of dexamethasone in the rabbit after subconjunctival injections for 26 days. Dexamethasone and silica release profiles in vitro and in vivo were compared with pharmacokinetic simulations made in silico. Dexamethasone was efficiently encapsulated within a visually white, homogenous, shear thinning and injectable hydrogel consisting of silica microparticles with an average diameter of 2.5 µm and a span of 3.5 µm. The hydrogel depot dissolved completely in vitro in sink in few days. In the rabbit study dexamethasone levels were measurable in both plasma and vitreous up to 26 days post injection. Pharmacokinetics was modelled in silico and a predictive tool was generated to support iterative formulation development. Silica hydrogel depot is a promising carrier material for subconjunctival injection of dexamethasone. Pharmacokinetic modelling is a useful tool for optimization of subconjunctival controlled release formulations and for refining the design of animal studies.

Chemical compounds studied: Dexamethasone, Silicic Acid, Non-porous Silica.