Silicone microspheres for pH-controlled gastrointestinal drug delivery

Silicone microspheres containing pH-sensitive hydrogels are prepared, characterized and evaluated for their potential pH-controlled gastrointestinal (GI) drug delivery. The pH-sensitive hydrogels are semi-interpenetrating polymer networks (semi-IPN(s)) made of varying proportions of poly(methacrylic acid-co-methylmethacrylate) (Eudragit (EUD) L100 or EUD S100) and crosslinked polyethylene glycol 8000 (P8000C). Up to 35 wt% hydrogel particles of mean volume diameters from 89 to 123 microm, medicated with 15 wt% prednisolone (PDN), are encapsulated, with 100% efficiency, into morphologically acceptable silicone microspheres in the 500-1000 microm size range, by a modified emulsion vulcanization method. Microspheres are eluted for 9 h with isotonic fluids at pH values increasing from 1.2 to 7.4, to simulate transit across the GI regions. PDN release depends on dissolution medium pH and on hydrogel composition, which determines hydrogel pH-sensitivity. With the P8000C-EUD L100 (1:2) semi-IPN, the release shows a marked peak at pH 6.8. The P8000C-EUD S100 (1:2) semi-IPN causes a gastroprotection and an almost uniform distribution of released drug between media at pH 6.8 and 7.4. With the P8000C-EUD S100 (1:1) semi-IPN, the dose fraction released to gastric fluid increases to match the values for the media at pH 6.8 and 7.4. With the pH-insensitive, highly swelling, P8000C, the largest dose fraction is released to the gastric medium and release is of Fickian type. With semi-IPNs, release depends weakly on the buffer molarity of the dissolution medium, a reduction from 0.13 to 0.032 of which renders the release rate to the media at pH 6.8 and 7. 4 more uniform.