Silicone microspheres for pH-controlled gastrointestinal drug delivery

Silicone microspheres containing pH-sensitive hydrogels are prepared, chara cterized and evaluated for their potential pH-controlled gastrointestinal ( GI) drug delivery. The pH-sensitive hydrogels are semi-interpenetrating pol ymer networks (semi-IPN(s)) made of varying proportions of poly(methacrylic acid-co-methylmethacrylate) (Eudragit (EUD) L100 or EUD S100) and crosslin ked polyethylene glycol 8000 (P8000C). Up to 35 wt% hydrogel particles of m ean volume diameters from 89 to 123 mu m, medicated with 15 wt% prednisolon e (PDN), are encapsulated, with 100% efficiency, into morphologically accep table silicone microspheres in the 500-1000 mu m size range, by a modified emulsion vulcanization method. Microspheres are eluted for 9 h with isotoni c fluids at pH values increasing from 1.2 to 7.4, to simulate transit acros s the GI regions. PDN release depends on dissolution medium pH and on hydro gel 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 P80 00C-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 P8 000C-EUD S100 (1:1) semi-IPN, the dose fraction released to gastric fluid i ncreases to match the Values for the media at pH 6.8 and 7.4. With the pH-i nsensitive, highly swelling, P8000C, the largest dose fraction is released to the gastric medium and release is of Fickian type. With semi-IPNs, relea se depends weakly on the buffer molarity of the dissolution medium, a reduc tion from 0.13 to 0.032 of which renders the release rate to the media at p H 6.8 and 7.4 more uniform. (C) 1999 Elsevier Science B.V. All rights reser ved.