Ketorolac entrapped in polymeric micelles: preparation, characterisation and ocular anti-inflammatory studies

Polymeric micelles made of copolymer of N-isopropylacrylamide (NIPAAM), vinyl pyrrolidone (VP) and acrylic acid (AA) having cross-linkage with N,N'-methylene bis-acrylamide (MBA) were used as host carrier in which up to 30%w/w ketorolac (free acid) was entrapped to make the formulation. The lyophilised powder was used for physical characterisation. The drug entrapment was found to be about 80% and the formulation was stable for 8-10 days at room temperature. The smaller the amount of ketorolac dissolved into the micelles, the longer was the formulation shelf life. The size of the particles as measured by dynamic light scattering was found to be around 35 nm diameter at 25 degreesC. TEM picture showed spherical particles. The structure of the polymer and its morphology were characterised by FTIR, NMR and XRD measurements. IR data indicated weak interaction between polymer and ketorolac in the encapsulated system. NMR spectra indicated rigid polymer backbone with intermittent iso-propyl group in the chain. XRD spectra showed significant loss of crystallinity of the drug while being entrapped in the polymeric micelles. The release of drug in aqueous buffer (pH 7.2) from the polymeric micelles at 25 degreesC were 20 and 60% after 2 and 8 h respectively and is temperature and pH dependent. In vitro corneal permeation studies through excised rabbit cornea indicated two fold increase in ocular availability with no corneal damage compared to an aqueous suspension containing same amount:of drug as in nanoparticles. The formulation showed significant inhibition of lid closure up to 3 h and PMN migration up to 5 h compared to the suspension containing non-entrapped drug, which did not show any significant effect. (C) 2000 Elsevier Science B.V. All rights reserved.