In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide

Abstract

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

“…A liquid dosage form becomes semisolid or solid via various mechanisms, such as thermal trigger [ 1 , 2 ], pH change [ 3 ], solvent exchange [ 4 ], and chemical reaction [ 3 , 5 ]. The system has been focused on various application sites, such as the eyeball [ 6 ], periodontal pocket [ 7 ], articular joint [ 8 ], and muscle [ 9 ]. The solvent exchange or antisolvent processes are one of the simple mechanisms that suit any life form, given that the biological fluid is located in almost every part of the being.…”

In vitro dissolution testing models of ocular implants for posterior segment drug delivery

“…The static diffusion approach has been widely used to quantify the release of different drugs from in situ depot forming implants [56,59,60]. The drug-loaded polymers were directly injected into glass vials containing the release medium.…”

Considerations for Polymers Used in Ocular Drug Delivery

“…Several labs are investigating additional polymer systems for intravitreal use. This includes our work developing polydopamine nanoparticles for anti-VEGF delivery, as well as efforts by other labs developing technologies such as phase-inversion mixtures of polymer and solvent, PEGylated siloxanes, and NIPAAmbased thermoresponsive polymers for intravitreal (130,229,230). Some of these systems are currently being translated for commercial use, such as ReVana Therapeutics' EyeLief TM and OcuLief TM injectable polymers (231).…”