ABSTRACT:
The aim of the study was to design pulsatile release capsule of Ramipril. Plasma norepinephrine level and plasma renin activity are elevated in the morning: both hormones have potential to induce coronary vasoconstriction therefore we can achieve peak plasma concentration of drug at morning and can control morning spate of B.P. compliances. The designed pulsatile drug delivery system consists of a semipermeable capsule body coated with water insoluble ethylcellulose containing hydrophilic swellable polymer, a core tablet of Ramipril was placed onto the compacted swellable polymer bad. An erodible tablet was inserted into the mouth of the capsule and positioned flush with the end of the coated body. The capsule body is closed with water soluble cap of hard gelatin. The lag time was controlled by the erosion of the matrix tablet and subsequent complete rupturing of the polymer coating, allowing fast drug release. The rapid release of the drug after a lag time consistent with requirement for chronotherapeutics was achieved with developed formulation M-6 (swellable polymer, xanthan gum, core tablet, C-2, erodible tablet; E-2 and 10 % w/w coated capsule body) which show lag time of 4 hr. During the lag time only 25 % drug released following rapid release (99.13 2 83 % in 7 hr.) of drug was observed. The ex- vivo absorption study conducted using everted chicken intestinal segment indicated delay in absorption of drug. Thus this approach can provide a useful means for time control release of Ramipril and may be helpful for patients with morning spate of BP.