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Nikita Malavia, Laxma Reddy, Istvan Szinai, Norman Betty, Justin Pi, Jeremiah Kanagaraj, Alisha Simonian, Robert Jennings, Glenn Stoller; Biodegradable Sustained-Release Drug Delivery Systems Fabricated using a Dissolvable Hydrogel Template Technology for the Treatment of Ocular Indications. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1296.
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Biodegradable drug delivery systems can provide a continuous drug supply to target sites for extended periods. These systems dramatically improve compliance by decreasing the burden of repeated injections in ocular diseases. A dissolvable hydrogel template technology was used to produce biodegradable microparticles custom designed in three dimensions for sustained release drug delivery.
In this study OHR1031, a small molecule drug for glaucoma, was incorporated into microparticles using a dissolvable hydrogel template technology. The drug was dissolved into a PLGA polymer-solvent mixture. The mixture was applied to templates with wells of uniform size that define the resulting microparticle size and shape. Templates were dissolved in water. Microparticles were recovered by filtration and dried. Particle size analysis was performed using a laser light scattering instrument. An in vitro release study was conducted in phosphate buffered saline at 37oC using conditions to ensure drug solubility did not impact drug release rates. Drug content in the microparticles and release media was measured by HPLC.
In this example, microparticles obtained using the dissolvable template technology had a median particle size of 60 μm with 80% of the particles within 10 μm (Figure 1). OHR1031 content in the microparticles was 57% w/w with almost 100% incorporation efficiency. Drug release rate was nearly zero-order for over three months with virtually no initial burst (Figure 2).
The hydrogel template technology is amenable to small molecules and biologics. It provides a means to achieve high drug content in biodegradable materials with high incorporation efficiency. Microparticles are recovered from readily soluble hydrogel templates. Any water insoluble material can be chosen as the microparticle matrix to achieve the desired release durations. The technology allows for precise control of size and shape of template wells in every dimension. The resulting microparticles have a narrow size distribution reflecting the size and shape of template wells. These attributes enable microparticle injection using narrow bore needles into sensitive ocular spaces of long acting drug products.
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