In vivo validation of the release rate and palatability of remoxipride-modified release suspension.
Remoxipride, a D2-dopamine receptor antagonist, is well tolerated and completely absorbed after oral administration. Because of its extremely bitter taste, an oral palatable suspension was developed by using a taste-masking microencapsulation. The bioavailability of remoxipride was investigated in two studies in healthy volunteers after administration of a 100-mg dose in suspension. The first study used a capsule as reference, and the second study a plain solution. Taste assessment was carried out in the second study. The extent of bioavailability was the same when comparing the oral suspension to a capsule and to a plain solution. However, the rate of absorption is delayed, and Tmax was 3.0 hr after the suspension, 1.0 hr after the oral solution, and 1.6 hr after the capsule. The release rate in vitro from the suspension was determined by applying the USP-paddle method. By using numerical convolution and deconvolution, the release rates in vivo and in vitro were shown to be similar when using water with 0.5% sodium lauryl sulfate as dissolution liquid. The taste-masked oral suspension is suitable for full-scale production, with good control of the encapsulation process and of the preparation of a suspension.
Sjöqvist
R
R
Research and Development Laboratories, Astra Arcus AB, Södertälje, Sweden.
Graffner
C
C
Ekman
I
I
Sinclair
W
W
Woods
J P
JP
D000328:Adult; D001682:Biological Availability; D002214:Capsules; D005260:Female; D006801:Humans; D008297:Male; D008863:Microspheres; D017330:Remoxipride / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012996:Solutions; D013535:Suspensions; D013649:Taste / Q000187:drug effects
D002214:Capsules; D012996:Solutions; D013535:Suspensions; D017330:Remoxipride