Background: Chronotherapeutics, the drug delivery based on circadian rhythm, is recently
gaining much attention worldwide. Various diseases like asthma, hypertension, and arthritis show the
circadian variation that demands time scheduled drug release for effective drug action. Therefore, the
pulsatile drug delivery system has been designed to confer preprogrammed drug delivery.
Objective: In the present study, a ‘3 Cap’ pulsatile drug delivery system has been developed, optimized,
and characterized in order to achieve the floating and pulsatile release of ramipril.
Methods: An optimal response surface design was employed to investigate the effect of isopropanol:
formaldehyde vapors for varying time on drug release from the capsules. ‘3 Cap’ pulsatile drug delivery
system was evaluated in terms of floating time, density, the effect of gastric flow rate, and type
of dissolution apparatus on drug release.
Results: Independent variables exhibited a significant effect on the drug release of the prepared formulations.
Results showed that time between the release of fractions of dose increased with an increase
in formaldehyde: isopropanol ratio and duration of exposure to formaldehyde vapors with no
effect of gastric flow rate.
Conclusion: The results of the designed system revealed that an optimum exposure of 1:2 of isopropanol:
formaldehyde vapors for sixty minutes resulted in the desired release of second pulse of dose
after a predetermined lag time of 5 hours as desired. ‘3Cap’ system was successful in achieving floating
and pulsed release of hypertensive drug opening a ‘new lease of life’ to the existing drug molecule.