Sustained Release Biocompatible Ocular Insert Using Hot Melt Extrusion Technology: Fabrication and in-vivo evaluation

• Published in: Journal of drug delivery science and technology 2022-05, Vol.71, p.103333, Article 103333
• Main Authors: Khan, Saeed Ahmad, Ma, Xiangyu, Jermain, Scott V., Ali, Hussain, Khalil, Islam A., El Fouly, Marwa, Osman, Ahmed H., Williams, Robert O.
• Format: Article
• Language: English
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103333

Topical eye drops usually have low bioavailability of the drug. Rapid turnover of lacrimal fluid flushes the drug away from the ocular surface, and the drug has limited time for absorption. Therefore, we design Metoprolol loaded ocular insert to enhance bioavailability against glaucoma in this study. Hot-melt extrusion was utilized to prepare the inserts using Gelatin, GelMa, and Polyacrylic acid (PAA) as matrix-forming polymers. The prepared ocular insert was characterized for physicochemical properties and in vitro drug release. It was observed that GelMa concentration and PAA concentration greatly affected drug release. Inserts prepared from Gelatin-PAA released 38.6% Metoprolol in the first hour. However, replacing 20% of Gelatin with GelMa reduced the initial release to 23.6%. Moreover, inserts prepared with 30% GelMa released 19% of the drug in the first hour, which exhibited a quasi zero-order release profile. The effect of PAA concentration on the release of the drug was also very evident. Inserts prepared with 5% PAA concentration released around 30% of the drug in the first hour, while those prepared with 20% PAA took 2 h to release a similar amount of drug. Similarly, 81% and 50% of the drug were released after 4 h from inserts containing 5% PAA and 20% PAA, respectively. Thus, it is clear that Metoprolol release can be tuned by varying the GelMa and PAA concentration in the formulation. The insert, which was able to sustain the drug release for 12 h, has the potential to be used as a good ocular delivery system, which requires less frequent dosing compared to eye drops. [Display omitted]