A Comprehensive Review of Thermo-Sensitive In Situ Gels for Ocular Drug Delivery: A Revolutionary Approach to Ocular Drug Delivery

Abstract

The development of thermo-sensitive in situ gels for ocular drug delivery offers a promising approach to overcome
the limitations of conventional eye drops, such as low bioavailability and rapid pre-corneal elimination. This
review provides a comprehensive analysis of the formulation development and evaluation of in situ gels for
delivering clarithromycin hydrochloride, a broad-spectrum antibiotic effective against various ocular infections.
Thermo-sensitive gels are designed to remain in liquid form at room temperature and undergo sol-to-gel transition
upon contact with ocular surface temperature, enhancing drug retention and sustained release. The selection
of polymers, such as Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose plays a pivotal role
in achieving desired gelation properties and biocompatibility. Critical formulation factors, including polymer
concentration, gelation temperature, and drug solubility, are discussed in detail. Evaluation parameters such
as physicochemical properties, in vitro drug release, antimicrobial activity, stability, and ocular irritation are
reviewed to ensure safety and efficacy. The advantages of this delivery system include prolonged drug retention,
reduced administration frequency, and improved therapeutic outcomes. Despite its potential, challenges in largescale
production, sterilization, and clinical validation remain. This review highlights recent advancements and
provides insights into future directions for developing patient-centric, effective ocular drug delivery systems
using thermo-sensitive in situ gels.