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Raghu Raj Thakur, Hannah McMillan, David S Jones; Injectable in situ-forming phase inversion implants for sustained intraocular drug delivery. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5263.
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This study evaluates effect of mucoadhesive polymers on the in situ-forming phase inversion implants for sustained intraocular drug delivery.
Phase inversion gel formulations containing PLGA, N-Methyl-2-pyrrolidone (NMP) and mucoadhesive polymers (MP) (e.g. HPC, HEC, HPMC, CMC and Carbopol), at different concentrations, were prepared and evaluated for rheological properties, syringeability, and mucoadhesiveness. Selected gels, containing fluorescein sodium (FNa) as model molecule, were injected into PBS to form implants and in vitro drug release was evaluated. Implant formation was examined using optical coherence tomography (OCT) and SEM. Compressibility of implants were determined using Texture Analysis.
The maximum force and work required in expelling gels through 27G needle was dependent upon the type & concentration of MP. For example, formulations containing HPMC and Carbopol showed < 36.45 N.mm of expulsion forces and HEC formulations showed > 54.63 N.mm, at different concentrations studied. Higher concentration of MP resulted in enhanced mucoadhesion. The rate of implant formation, studied using OCT & SEM, was as follows HEC > CMC > HPC > Control > Carbopol > HPMC. The rate of implant formation also affected the release of FNa from implants. For e.g., formulations containing 2.5% HEC, 15% CMC, 5% HPC, Control (i.e., without MP), 1.5% Carbopol and 0.5% HPMC showed 61%, 59%, 46%, 34%, 19% and 12% of burst release, respectively. Implants with greater burst release had shorter lifespans e.g., formulations with HEC, CMC, and HPC showed FNa release for 42, 35, and 45 days, respectively. Carbopol and HPMC implants showed release for 57 and 55 days respectively. Compressibility of implants, measured after 24 h, was also affected by the type and concentration of MP. For e.g., 1.5% HPMC implants required 2.02 N of force compared to 3% CMC implants that required only 0.43 N of force.
In this work we have achieved a significant reduction in burst drug release from in situ forming phase inversion implants by addition of mucoadhesive polymers. Results suggest the formulations containing HPMC or Carbopol show the most potential for further study due to their low viscosity, work of syringeability, mucoadhesive capabilities, reduction in burst release and sustained delivery. This drug delivery system can provide sustained intraocular drug delivery.
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