Supercritical impregnation of polymer matrices spatially confined in microcontainers for oral drug delivery: Effect of temperature, pressure and time

The present study is aimed to enhance the oral bioavailability of ketoprofen by inserting it into the matrixof poly(vinylpyrrolidone) (PVP) K10 spatially confined into microcontainers, by means of supercriticalCO2-aided impregnation. Microcontainers are cylindrical reservoirs, with typical sizes in the micrometerrange, with a cavity open on one side, where the drug formulation is loaded.

Differently to traditionaltablets, microcontainers have a higher surface area per unit volume, and release the drug only in onedirection. This design is meant to enhance the absorption of problematic drugs, like those with poor sol-ubility in water. In a previous study we introduced a novel technique for drug loading of microcontainers,based on inkjet printing and supercritical impregnation (SCI).

We showed that SCI produces accurate andreproducible drug loading for large arrays of microcontainers. In the attempt of enhancing the throughputof the loading methods, we propose the replacement of polymer inkjet printing with an easier man-ual compression of the PVP powder into the microcontainers.

As the second step, the polymer powderfilled-microcontainers were submitted to SCI. The separate role of different impregnation parameters(temperature, pressure, time, drug concentration in the supercritical phase) was elucidated with respectto the loading capacity. The microcontainer filling was observed by means of optical macroimaging, X-ray microtomography and scanning electron microscopy.

The physical state of the drug was investigatedby means of Raman spectroscopy and compared with selected representative PVP-ketoprofen physicalmixtures. Finally, the drug loading was estimated by means of in vitro dissolution tests.The characterization study shows that the present loading method is a valuable alternative to the onepreviously described.

The drug loading can be controlled with high accuracy and reproducibility andthe impregnated drug is in amorphous state. These results demonstrate that SCI can be used as a highthroughput loading technique for microfabricated devices for oral drug delivery.