Bioavailability of starch based hot stage extrusion formulations

The aim of the study was to develop a starch based hot stage extrusion form ulation for controlled drug delivery and to evaluate its in vivo behavior. The extrusion mixture consisted of 53% corn starch as the matrix forming ag ent, 15% sorbitol as a plasticizer, 30% theophylline monohydrate as the mod el drug and 2% glyceryl monostearate as a lubricant. The extrudates were pr oduced by means of a corotating twin screw extruder of APV Baker equipped w ith a twin screw powder feeder and a 3-mm cylindrical die. During extrusion 20% water (based on the wet mass) was added to the powder mixture. The ext rudates were dried in an oven at 60 degrees C during 48 h, cut and filled o ut in hard gelatine capsules, in a way that the content of two capsules cor responded with a dose of 300 mg anhydrous theophylline. The dissolution pro file of the experimental dosage form was retarded with a drug release of ar ound 80% in 8 h. The in vivo behavior of the experimental formulation was e valuated in a randomized crossover design study (n = 8) with a commercially available multiple unit sustained release product as the reference formula tion. The plasma samples were analyzed by a validated HPLC-UV method with S olid phase extraction for the sample preparation. It was clear that the exp erimental formulation exhibited sustained release behavior, but that it per formed less well than the multiple unit dosage form. (C) 1999 Elsevier Scie nce B.V. All rights reserved.