Preparation and Bio Pharmaceutical Evaluation of Chrono Pharmaceutical Drug Delivery System of Atenolol

Abstract

A time-adjustable pulsatile release system containing atenolol as an active pharmaceutical agent was developed for bedtime dosage administration and release of medicine in the early morning to manage elevated blood pressure. The system contained an immediate release (IR) core, a sustained-release (SR) plug, and a mucoadhesive cup layer and it was designed by the cup and core technique. The immediate-release layer was composed of atenolol, croscarmellose sodium, microcrystalline cellulose (MCC), sorbitol, talc, and magnesium stearate. The SR plug was composed of hydroxyl propyl methylcellulose (HPMC), polyvinyl pyrrolidine (PVP), MCC, Lactose, talc, and magnesium stearate. The mucoadhesive cup contains polycaprolactone and mucoadhesive polymer chitosan. Bilayer tablets were punched by applying different compressive forces. Based on the Release data of the drug from each layer F5 and S5 were selected for the preparation of the bilayer tablet. Cup composition containing 3% of chitosan provided the highest mucoadhesion time up to 10h. Pulsatile delivery of the drug from the formulation was observed at 300 min after the administration of the drug. The constructed pulsatile delivery systems were compared to that of commercially available atenolol IR tablet. The comparison demonstrated that the formulation is suitable for the intended chronopharmaceutical delivery of antihypertensive drugs. Keywords: Chronopharmaceuticals, Pulsatile Drug Delivery, Hypertension, Mucoadhesive Polymer, Atenolol