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Jennifer Haley, Janet Tully, Mari Yang, Stuart Williams, Jeremy Hansen; Development of Dissolution Assays for Ocular Implants. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5674.
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© ARVO (1962-2015); The Authors (2016-present)
In-vitro drug release assays are an essential cost-effective tool for developing extended release ocular implants. The assays are used to screen formulations for drug release rates to understand the potential in vivo performance, as well as batch-to-batch consistency. Various real-time in vitro dissolution assays were developed to differentiate release rates between dexamethasone implant formulations and an accelerated method was subsequently developed for verifying product quality for batch release in a timely manner.
Extended release dexamethasone containing implants were characterized using multiple dissolution method parameters and measured using RP-HPLC. Real-time release rates were evaluated at 37°C in buffered and unbuffered media. The effects of different surfactants, (anionic, cationic, and non-ionic), were evaluated in 1X PBS, pH 7.4. Accelerated release rates were determined in 1X PBS, pH 7.4 with 0.1% Triton X-100 at multiple temperatures.
Ultra-pure water, 0.1X PBS pH 7.4, 1X PBS pH7.4 and 0.9% Saline pH 6.1 were evaluated as potential release media and showed different in vitro release profiles. The addition of surfactants CTAB, SDS and Triton to the release media was also evaluated. For real-time dissolution at 37°C the use of 1X PBS, pH 7.4 with 0.1% Triton X-100 showed extended release profiles with the sensitivity needed to differentiate between formulations. The dissolution method using 1X PBS, pH 7.4 + 0.1% Triton X-100 was evaluated at varying temperatures for accelerated release. Samples tested at 44°C successfully accelerated release while maintaining the sensitivity to discriminate between batches with different real-time dissolution rates.
Real-time and accelerated dissolution methods were developed for extended release dexamethasone implants. These methods demonstrate the ability to differentiate release rates in vitro to select formulations to progress to further development stages and the ability to more rapidly identify differences from batch to batch for product release.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure 1: (A) A real-time dissolution method using 1X PBS, pH 7.4 + 0.1% Triton X-100 at 37°C showed an extended drug release profile with the sensitivity to differentiate between minimal formulation differences. (B) The accelerated dissolution method at 44°C showed the ability to discriminate between batches for product release purposes.
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