Development and In vivo evaluation of immediate release amlodipine besylate and nebivolol hydrochloride coated pellets using 32 full factorial design by novel liquid layering technology

Abstract

The aim of the present investigation was to development of immediate release liquid coated pellets of poorly soluble drugs Amlodipine besylate (AMD) and Nebivolol HCl (NBV) by novel liquid layering technology to enhance solubility and bioavailability with HPC-EF as hydrophilic polymer and PVP K 30 as binder. A 32 full factorial design was employed to optimize the formulation of pellets. In order to optimize formulations, two polymers HPC-EF and PVP K 30 as factors and amount of polymers (three different concentrations), were taken as independent variables. All the formulations were evaluated for particle size, friability, moisture content, drug content, in vitro dissolution studies and in vivo bioavailability studies. All the formulations were found uniform with respect to all evaluation parameters. The optimized formulation (F5) showed highest % of drug release 99.59 by the end of 8 min for AMD and 99.21 % of drug release for NBV, when compared with the marketed product (NEBISTAR-AM) the percentage of AMD and NBV was 83.91 and 82.67 respectively within 8 min, by using 4% of HPC-EF and 1% of PVP K 30. SEM confirmed that F5 was spherical in shape with a smooth surface. In vivo studies indicated significant difference in the bioavailability between AMD and NBV coated pellets with pure drug. Clinical data confirmed that the optimized formulation (F5) by choosing immediate release drug coated pellet technology by liquid layering method could improve patient compliance and ensure better disease management when compared with the marketed product.