Abstract: Disclosed are depot formulations comprising a biodegradable silica hydrogel composite, wherein the hydrogel composite comprises (i) a silica hydrogel; and (ii) a plurality of microparticles comprising silica and an oligopeptide or a peptidomimetic compound, or a pharmaceutically acceptable salt thereof. The depot formulations described herein provide sustained, long-term release of the active pharmaceutical compound. The depot formulations may be implanted in the eye and are useful for treating ocular diseases. The plurality of microparticles comprising silica and an oligopeptide or a peptidomimetic compound, or a pharmaceutically acceptable salt thereof can be prepared using a continuous flow process.