Statistically-Based Optimization of Verapamil Hydrochloride Loaded Gastroretentive Alginate Beads

Abstract

Objectives: A gastroretentive drug delivery system is one of many oral drug delivery systems developed to improve drug bioavailability and control drug release. It allows prolongation of drug gastric residence period for several hours. Verapamil Hydrochloride (VerHCl) is a good candidate for gastro retention because it has narrow absorption window and short half life. The goal of this study was formulation and evaluation of optimized VerHCl loaded gastroretentive alginate beads for increasing drug bioavailability and decreasing its dosing frequency. Methods: VerHCl loaded alginate beads were prepared according to 2 3 full factorial design using ionotropic emulsion gelation method. The effect of three formulation variables; oil concentration (%w/v) (X1), polymer concentration (%w/v) (X2) and drug to polymer ratio (X3) was investigated on mean diameter (Y1), drug loading % (Y2), entrapment efficiency (EE%) (Y3), % drug released at 1 (Y4), 5 (Y5) and 8 hr (Y6). The optimized formula was further assessed in terms of in vitro floating, in-vitro drug release, in vivo gastro retention in rats and flowability. Results: Design-Expert® numerical optimization revealed that optimum formulation levels for VerHCl loaded alginate gastroretentive beads were; oil concentration (X1) = 17.2 %w/v, polymer concentration (X2) = 4.34 %w/v and drug to polymer ratio=1.2. The optimized formula exhibited yield% (85.63± 2.65%), Drug loading% (13.60±0.89%), EE% (60.11± 2.52%), prolonged floatability with no initial lag time, sustained in vitro drug release over 8 hr, gastroretention in rats over 8 hr and good flowability. Conclusion: The optimized formula of VerHCl loaded alginate beads could be promising for retaining VerHCl in stomach for a prolonged time which could possibly be advantageous in terms of bioavailability and patient compliance.