Development, optimization and in vitro-in vivo evaluation of solid lipid microparticles for improved pharmacokinetic profile of bisoprolol

Abstract

The current research aimed at designing and optimizing controlled release solid lipid microparticles (SLMs) of Bisoprolol (BPL) from biocompatible waxes by using Box-Bhenken design (BBD) for improving the drug pharmacokinetics, enhancing compliance in hypertensive patients as well as eliminating inefficiencies of traditional methods of drug delivery. Seventeen formulations (F1 to F17) of controlled release BPL loaded SLMs were made by melt emulsification technique where Carnauba wax (CW) and Ceresin wax (CSW) were used as carriers and Tween 80 was used as stabilizer. The SLMs were characterized using fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Results revealed that micromeritics properties of all SLMs were satisfactory and showed good percentage yield (PY) and entrapment efficiency (EE). The minimum EE was observed by formulation-1 (F1) as 21.66% whereas F3 has showed maximum EE as 88%. Results of in vitro release study revealed that all formulations showed a well-controlled release in simulated intestinal medium at pH 7.4. The formulation F3 with high wax concentration revealed best extended release characteristics (29%) in 12 h. The pharmacokinetics studies of SLMs demonstrated an expressively lower Cmax (maximum plasma concentration) of BPL (53.61 ± 2:52) with a satisfactorily higher time to achieve maximum plasma concentration (Tmax) of 10.24 h as compared to Cmax (79.63 ± 5.75) and Tmax (2.45 ± 3.83) of BPL released from commercial brands. Moreover the attainment of greater bioavailability of BPL was most probably due to the increase in half-life (20.44 ± 2.82), mean residence time (24.81 ± 4.22) and area under the plasma concentration level curve (AUC0–24) of 9688.6 ± 4.18 for BPL released from SLMs. Convincingly, the inventive technique could not only sustain the drug release in the in vitro and in vivo environment but also maintain the plasma drug concentration level constant for a longer time without elevating Cmax.