ReviewFoundationIn vitro and in vivo evaluation of in situ gelling systems for sustained topical ophthalmic delivery: state of the art and beyond

- A guideline for the development of ophthalmic in situ gelling systems is proposed.
- Gelation, gelation kinetics and rheological characterization methods are discussed.
- Mucoadhesive systems and their characterization techniques are reported.
- In vitro release and ocular toxicity assays are reviewed.
- In vivo characterization of sustained release and retention time is discussed.

In situ gelling delivery systems for the ocular administration of drugs has been a major focus of research over the past two decades, improving the treatment of diseases of the anterior segment of the eye by simple, safe, and reproducible drug administration. This drug delivery strategy results in high ocular bioavailability by avoiding rapid precorneal clearance resulting from nasolacrimal drainage and eye blinking. However, the development of such unconventional forms requires many parameters to be mastered, such as gelation time, viscoelastic behavior, mucoadhesion, and sustained release. In this review, we describe and assess the in vitro and in vivo methods available for in situ gelling ophthalmic delivery systems, highlighting the advantages of existing methods and, in some cases, the need for more relevant assays.