Ocular In- situ gelling systems: An advance

ophthalmic drug delivery systems.

Abstract
Delivery of drug into the ocular region is hindered by the protective layers that encapsulate the eyes, it has always been a major
problem to get an effective bioavailability of the active drug in the ocular region due to the low precorneal resident time of most of
the ocular delivery systems specifically convention once such as ointment, solution and suspension, as a result, most of the delivery
systems are not capable of effectively treating ocular diseases. Several works have and are being carried out to overcome this
problem one of which is using in-situ forming polymeric systems. Ocular In-situ gelling systems are a novel class of ocular drug
delivery systems that are initially in a solution form but instantaneously gets converted into a viscous gel upon introduction or
installation in the ocular cavity from which the active drugs get released in a sustained manner. This sol-to gel phase transition
depends upon various factors like change in pH, ion presence and change in temperature. Gel formed after the transformation has
preferred viscosity along with bio-adhesive property, which increases the gel’s resident time in the ocular area and also releases the
drug in a prolonged and sustained manner unlike conventional eye drops and ointments. This review emphasizes various ocular in-
situ systems namely, pH triggered, Ion activated, and Temperature triggered systems which have prolonged residence time in the cul-
de-sac area of the eye, hence increasing the ocular bioavailability.

Introduction
Ocular drug delivery is challenging due to protective barriers
like tear production, blinking, and the corneal epithelium,
which limit drug penetration and retention. These factors result
in rapid drug clearance, requiring frequent administration to
maintain therapeutic levels.
Conventional drug delivery methods, such as eye drops and
ointments, suffer from rapid drainage and low bioavailability,
often below 5%. Frequent dosing is needed, reducing patient
compliance and treatment effectiveness.
In-situ forming polymeric drug delivery systems offer a Conclusion
promising solution. These formulations are applied as liquids In-situ gelling systems represent a promising innovation in
and transform into gels upon exposure to ocular physiological ocular drug delivery by addressing the challenges of rapid drug
conditions, such as pH changes, temperature variations, or ion clearance and poor bioavailability associated with conventional
activation. This transition prolongs drug residence time, formulations. These advanced systems utilize physiological
minimizes drainage, and enhances bioavailability, leading to triggers such as pH changes, temperature variations, and ion
sustained drug release and improved patient adherence. activation to transform from a liquid to a gel upon
administration. This phase transition significantly enhances
Mechanism of In-Situ Gelling drug residence time, ensuring sustained release and reducing
the need for frequent dosing. As a result, patient compliance
Systems and therapeutic efficacy are greatly improved. While these
In-situ gelling systems are liquid formulations that undergo a systems offer numerous advantages, continued research and
phase transition into a gel upon exposure to physiological development are necessary to optimize their formulation,
conditions such as pH, temperature, or ionic concentration. This safety, and clinical applications, paving the way for more
transition prolongs drug residence time and enhances ocular effective and patient-friendly ophthalmic treatments.
drug delivery.
• pH-triggered systems: These formulations remain in a sol References
(liquid) state at low pH but form a gel when exposed to the 1. Chhetri P, Chakraborty P, Das D, Afnan T. In-Situ
higher pH of the tear fluid (~7.4).Example: Carbopol - A Forming Polymeric Drug Delivery Systems for
weakly acidic polymer that undergoes gelation in response Ophthalmic Use: An Overview. Journal of Drug Delivery
to an increase in pH, providing controlled drug release. and Therapeutics. 2021; 11(3-S):98-103.
• Ion-activated systems: These rely on ionic interactions with 2. Kumar SP, Kavitha K, Rupesh kumar M. Recent
tear fluid components (such as calcium and sodium ions) to developments and strategies of ocular in-situ drug
form a gel .Examples: Sodium alginate, Gellan gum - These delivery systems: a review. Int J Pharm Clin Res. 2013;
polymers interact with divalent cations (e.g., Ca²⁺) in tear 5:64-71.
fluid to undergo gelation, enhancing drug retention. 3. Rajoria G, Gupta A. In-situ gelling system: a novel
• Temperature-triggered systems: These solutions remain in a approach for ocular drug delivery. AJPTR. 2012; 2:24-53.
liquid state at room temperature but form a gel when 4. Ramya DD, Abhirami M, Brindha R, Gomathi S,
exposed to body temperature (~35-37°C).Examples: Vedhahari BN. In-situ gelling system-potential tool for
Poloxamers (Pluronics), Xyloglucan - Poloxamers exhibit improving therapeutic effects of drugs. International
reverse thermal gelation, meaning they transition from sol Journal of Pharmacy and Pharmaceutical Sciences. 2013;
to gel as the temperature increases, ensuring prolonged drug 5(3):27-30.
release.

National Seminar on “Sustainable Drug Chemistry- Balancing Innovation with environmental