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Ocular Delivery of Metformin for Sustained Release and in Vivo Efficacy
Vara Prasada Rao Regu1, Dhananjay Behera1, Sai Prathyusha Sunkara1
1Drug Development and Analysis Laboratory, School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India.
Abstract:
Metformin is known to lower inflammation, independent of its anti-diabetic action. Thus, topical metformin can be a therapeutic strategy for managing ocular inflammation associated with diabetes. To achieve this and address the issues of ocular retention and controlled release an in situ gel of metformin was developed. The formulations were prepared using sodium hyaluronate, hypromellose, and gellan gum. The composition was optimized by monitoring gelling time/capacity, viscosity, and mucoadhesion. MF5 was selected as the optimized formulation. It showed both chemical and physiological compatibility. It was found to be sterile and stable. MF5 exhibited sustained release of metformin for 8h that fitted best with zero-order kinetics. Further, the release mode was found to be close to the Korsmeyer-Peppas model. Supported by an ex vivo permeation study, it showed potential for prolonged action. It showed a significant reduction in ocular inflammation that was comparable to that of the standard drug. MF5 shows translational potential as a safe alternative to steroids for managing ocular inflammation.
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