Development andevaluation of prolonged release topical indomethacin formulations for ocularinflammation

Author(s): AdelliGR, Balguri SP, Punyamurthula N, Bhagav P, Majumdar S

Abstract

Purpose: Indomethacin (IN), a non-steroidal anti-inflammatory agent (NSAID) is used in the treatment of ocular inflammation. The aim of the present project is to evaluate ocular delivery and disposition of IN from various topical modified release ophthalmic formulations.

Methods: IN polymeric matrix film (IN-F) was prepared using melt cast method. Polyethylene oxide N10 (Mol.wt: 100,000 Daltons) was used as a matrix forming material. A polymeric film (4 mm x 2 mm; 0.2-0.4 mm thickness) consisting of 20% w/w drug load was used. IN-solution (IN-SOL) and IN-solid lipid nanoparticles (IN-SLN) formulations were prepared as per previously reported techniques. IN-F, 0.1% w/v IN-SOL, 0.1% w/v IN+2.5% w/v hydroxypropyl betacyclodextrin (IN-HPβCD) and 0.1% w/v IN-SLN formulations were evaluated in vitro with respect to release (2 h) and transcorneal flux (3 h) and also in vivo with respect to ocular tissue concentrations at the end of 2 h post topical instillation in anesthetized male New Zealand white rabbits. All animal studies were conducted following IACUC approved protocols.

Results: IN content in all the formulations was found to be within 95 -102% of theoretical value. Percentage release of IN from the film was 43.9 ± 3.1 % within the time period tested. Transcorneal flux across the isolated rabbit cornea was 2.8 ± 0.4 µg/min/cm2. Precorneal loss of IN from the film was observed to be 33.2%. Particle size, polydispersity index & entrapment efficiency of IN-SLN were found to be 226 ± 5 nm, 0.25 & 94.7 %, respectively. Transcorneal permeability of IN-SOL, IN-HPβCD and IN-SLN was observed to be 2.7 ± 0.48 x 10-6, 4.0 ± 0.9 x 10-6 and 12.2 ± 1.9 x 10-6 cm/s, respectively. The IN-SLN and IN-F formulations were significantly better than the solution formulations tested in vivo.

Conclusions: The results from these studies suggest that high levels of IN can be maintained in the ocular tissues for prolonged periods of time using the SLN and IN-F formulations. Further studies with these compositions, evaluating IN ocular tissue concentrations as a function of time post application, are ongoing.

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