Design, formulation and evaluation of multiparticulate time programmed system of ramipril for pulsed release: An approach in the management of early morning surge in blood pressure

Abstract

The intent of the present study was to develop and evaluate multiparticulate pulsatile release system from the solid dispersion of ramipril to minimize the risk of cardiovascular events associated with early morning surge in blood pressure. Solid dispersion was prepared by solvent evaporation technique using β-cyclodextrin (β-CD) and polyvinyl alcohol (PVA) as carrier. In this study, the effect of PVA on β-CD solubilization of ramipril was investigated. The formulation was characterized by FTIR, DSC and X-ray diffraction analysis. Release rate indicated that addition of PVA showed significant enhancement of solubility of ramipril. The optimized formulation (SD5) showed 96±4.1% in 30 min and selected for the preparation of pulsatile release system. The system consisting of a core containing drug coated with an inner swelling layer of HPMC E5 and Ac-Di-Sol ® followed by an outer enteric coating layer of ethyl cellulose and Eudragit ® L100-55. It was observed that higher level of swelling layer enhanced the rapid release whereas higher level of polymeric layer enhanced the lag time but delayed the drug release. In vitro optimized formulation showed 7.42 ± 2.6% drug releases in first 5 h (lag time) followed by rapid drug release 96.55 ± 2.28% in 5 h. The in vivo data indicated that C max (3.81 μg/ml) and AUC (0-24) (7473.89 μg.h/ml) of optimized formulation was significantly increased (1.43 fold and 8.07 fold respectively) as compare to marketed tablet. Thus, the system can be a promising approach for the management of early morning surge in blood pressure with increased the solubility and bioavailability of ramipril.