Determination of the dissolution behavior of celecoxib-eudragit E 100-nanoparticles using cross-flow filtration
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Abstract
This study deals with the development of a dissolution test method for nanoparticulate dosage forms. Thereto, nanoparticles (NPs) consisting of celecoxib as model drug and Eudragit E 100 were prepared by emulsification-diffusion and nanoprecipitation using a bench-top approach and MicroJetReactor(MJR). MJR is an enhanced impinging jet technology, which, besides the jets for solvent- and non-solvent phase, implements the use of a third jet carrying inert gas to facilitate fast depletion of the organic solvent. NPs were characterized using photon correlation spectroscopy (size, -distribution and zeta potential), scanning electron and atomic force microscopy (size and shape), HPLC and UV-Vis spectroscopy (API content) as well as differential scanning calorimetry and infrared spectroscopy (NP structure). Hence, almost spherical NPs of narrow size distribution with Z-Average of 200–450 nm, zeta potential of 40–50 mV and entrapment efficiency of 70–90 % were obtained. Dissolution tests were conducted using cross-flow filtration (CF); a new approach in pharmaceutical dissolution testing. This method, contrary to dead-end filtration, excludes the risk of filter clogging which is an important issue if NPs are present. Compared to in-situ approaches it is more robust and less expensive. Prior to investigations, the applicability of CF modules was successfully tested. Thereto, comparative photon correlation- and UV-spectroscopic measurements of nanosuspension and filtrate were performed. Different media were examined towards their suitability to achieve at least 85 % dissolution in 60 min. Hence, a medium, phosphate buffer pH 2.0 including 0.3 % cetrimide was found to be most suitable since both dissolution of Eudragit E (due to acidic pH) and sink conditions for celecoxib are given. Different filters were compared, while it was found that pore size must be sufficiently high to enable micelles including solubilized analyte to pass. Finally, the dissolution behavior of NPs of different size was compared, while there was no statistically significant difference.