Ocular Delivery of Metformin for Sustained Release and in Vivo Efficacy

Vara Prasada Rao Regu; Dhananjay Behera; Sai Prathyusha Sunkara; Vinit Gohel; Shyamalendu Tripathy; Ranjit Prasad Swain; Bharat Bhusan Subudhi

doi:10.1016/j.xphs.2023.04.002

Ocular Delivery of Metformin for Sustained Release and in Vivo Efficacy

J Pharm Sci. 2023 Sep;112(9):2494-2505. doi: 10.1016/j.xphs.2023.04.002. Epub 2023 Apr 7.

Authors

Vara Prasada Rao Regu¹, Dhananjay Behera¹, Sai Prathyusha Sunkara¹, Vinit Gohel², Shyamalendu Tripathy¹, Ranjit Prasad Swain¹, Bharat Bhusan Subudhi³

Affiliations

¹ Drug Development and Analysis Laboratory, School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India.
² Drug Development and Analysis Laboratory, School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India; ProCyto Labs Pvt Ltd., KIIT-TBI, Bhubaneswar, Odisha 751024, India.
³ Drug Development and Analysis Laboratory, School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India. Electronic address: bharatbhusans@gmail.com.

PMID: 37031863
DOI: 10.1016/j.xphs.2023.04.002

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.

Keywords: Diffusion; Mechanical properties; Ophthalmic drug delivery; Polymeric drug delivery system(s); Residence time(s); Viscosity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Delayed-Action Preparations / chemistry
Drug Delivery Systems
Eye*
Gels / chemistry
Humans
Hypromellose Derivatives / chemistry
Inflammation*

Substances

Delayed-Action Preparations
Hypromellose Derivatives
Gels