Posterior segment disorders represent a leading cause of vision impairment worldwide and remain challenging to manage due to limitations in ocular drug delivery. Although intravitreal injections of triamcinolone acetonide (TA) are effective, they are invasive and require repeated administration, highlighting the need for sustained-release systems. This study aimed to develop in situ sustained-release formulations of TA using lipid liquid crystals (LLCs). Formulations were prepared with glyceryldioleate (GDO), phosphatidylcholine (PC), and 28% w/w N-methyl pyrrolidone (NMP) at PC:GDO ratios of 50:50, 40:60, and 60:40. Additionally, a TA-hydroxypropyl-β-cyclodextrin (HPβCD) complex was prepared. The formulations were characterized for rheological properties, morphology, degradation behavior, and water uptake. In-vitro release was assessed in phosphate-buffered saline (pH 7.4), while in-vivo pharmacokinetics were evaluated in rabbits, comparing a selected LLC formulation (right eye) with a TA suspension (left eye). The F5 formulation (40:60 PC: GDO) achieved sustained release of 35.4% over one month and exhibited superior stability, with 24.9% less degradation compared to F6 (60:40 PC: GDO), which showed undesirable drug crystallization. The TA-HPβCD complex demonstrated an even slower release (28%). F4 (50:50 PC: GDO) was selected as optimized formulation, demonstrated the lowest water absorption and degradation with consistent release profile. In-vivo studies further confirmed that LLCs provided a more controlled and prolonged release compared with conventional TA suspension. In conclusion, LLC-based formulations of TA offer a promising strategy for sustained intravitreal drug delivery. Their biodegradability, ease of preparation, and ability to provide prolonged therapeutic levels highlight their potential for improving the management of posterior ocular diseases.
The present work describes the development and optimization of a poly (lactide-co- glycolide) based sustained release injectable microsphere formulation of exenatide using a coacervation and in oil drying process. The internal phase composition, containing exenatide and stabilizer, were evaluated to identify critical parameters affecting stability, drug loading, particle morphology, and burst release of exenatide. Incorporation of chondroitin sulfate(0.5-2% w/w), formed stable uniform coacervates providing consistent particle size distribution, drug loading up to 4.7% w/w, initial burst (<1%) and impurities, with "shrunken" microsphere morphology. The secondary emulsification temperature of 2-8 °C produced smaller and more uniform particles. A gradient quenching process for hardening of microspheres using n heptane: diethyl ether (1:9) to (10:0) provided low porosity and burst release relative to n-Heptane alone. The drying and lyophilization conditions reduced residual solvent levels (<5000 ppm or below quantitation) and improved its wetting characteristics. The formulation remained stable for 24 months at 2-8 °C, with minimal loss of assay content. In vitro release showed controlled release for over one month. This translated into approximately 28 days of drug exposure in rat pharmacokinetic studies and sustained glycemic control for 28 days in a db/db mice, thus, correlating microsphere erosion, in‑vitro release, and in‑vivo outcomes. This study provides insight into the manufacturing process dynamics.
