Dual-pulse Release System of Atenolol: Preparation and in-vitro Characterization

Abstract:

Aim: Hypertension exhibits a circadian rhythm and drugs need to be released at the time when the blood pressure is elevated most. This elevation is pronounced at 7 pm and at 4 am. Atenolol is an anti-hypertensive drug with an absorption window mainly in the upper section of the gastrointestinal tract. The present investigation was aimed at designing floating pulsatile capsules for dual release of atenolol in the stomach for effective management of hypertension. Materials and Methods: The floating pulsatile capsules designed had different components: a formaldehyde-treated capsule body; an untreated cap; a polymer plug layer, containing a polymer; two atenolol-containing immediaterelease tablets and a swellable polymer layer. The polymer plug layer was made of hydroxypropyl methylcellulose (K4M or E50) and xanthan gum alone or in combination. The capsules were characterized for weight variation, percent drug content, in-vitro release behaviour and floating property. Results: The outcomes of the in-vitro studies showed that lag duration between the two pulses of drug release from the formulations can be adjusted by manipulating the composition of the plug layer. The optimized floating pulsatile capsule provided the first pulse of the drug immediately after administration to cover the first point of the symptoms. It provided the drug release from second pulse after a lag time of 8 hr for covering up the second point of the symptoms in the early morning. Conclusion: Thus, the dual-release floating pulsatile capsule designed may be used for chronological treatment of hypertension.

Keywords: Hypertension, Pulsatile, Floating, Lag time, Capsule, Plug layer.