Development of a three compartment oral sustained release delivery system for nifedipine: An in vitro and in vivo comparison with an osmotic pump delivery system, in the dog

The "Triad Capsule" is thought to be a good candidate for development of a new "One-a-day", sustained release delivery system, for a variety of orally administered drugs. The "Triad Capsule" consists of three individual compartments. The first compartment is coated on the outside of the capsule. A hard gelatin capsule houses the remaining two compartments. The second compartment (granules) is the intermediate releasing compartment and the third is the sustained releasing compartment, in the form of pellets. In vitro the "Triad Capsule" delivered Nifedipine immediately and sustained its release for up to 18-20 h. In contrast, the GITS-Nifedipine (Procardia-XL{dollar}sp{lcub}circler{rcub}{dollar}) sustained the release of the drug in a zero-order manner, for 24 h, after an initial lag time of 2-4 h. In the present study, a four way cross-over study was performed in beagle dogs (n = 4), to compare the performance of radiolabelled "Triad Capsule" (30 mg) versus radiolabelled GITS-Nifedipine tablet (30mg), under fasted and fed conditions. Concentrations of Nifedipine (30-50 ng/mL) were detected immediately in the serum following the administration of the Triad Capsule and concentrations of 20-95 ng/mL were maintained for up to 24h. However, two hours post administration of the GITS, no Nifedipine was detected in the blood. Concentrations of 20-80 ng/mL were achieved from the GITS for the following six hours, but no drug was detected beyond 8 h post dose.; Under fed conditions both delivery systems resided in the stomach for periods exceeding 10h. The blood levels of Nifedipine, post administration of the Triad Capsule, reached concentrations of 15-40 ng/mL within the first hour. Also, from 8 h onwards, concentrations of Nifedipine (20-65 ng/mL) were maintained. In contrast, when the GITS tablets were administered to the dogs under fed conditions Nifedipine was released within the first hour. The GITS tablets were capable of sustaining concentrations in the range of 10-60 ng/mL in the blood for up to 24 h. These studies demonstrated that the Triad Capsule was a viable alternative to the GITS. Of particular interest, is the fact that the Triad Capsule exhibited a more consistent performance in the manner in which the drug was released and absorbed, compared to the GITS tablet.