Design, Optimization and Pharmacokinetic Profiling of BCS Class II Drug Loaded Oral Self Nanoemulsifying System
摘要
The orally administered self nano emulsifying drug delivery system (SNEDDS), an uniform blend with nano scaled globules, is composed of oil, surfactant and co-surfactant. The aim of the investigation was to develop and optimize Nicardipine loaded liquid SNEDDS via Box Behnken design and characterised based on physicochemical features, DSC and stability profile. Further to achieve sustain drug release, the optimized SNEDDS was compressed as self nano emulsifying tablet (SNET). Furthermore, the in vivo and pharmacokinetic study of the drug loaded SNET (NT) were performed. The NOF indicated droplet size (75.62 nm ± 2.01), self emulsification time (37 s ± 1.01), and 87.6% ± 0.08drug release (at 1 h). The bias was found to be within the range of -0.72 to + 1.19 for stable, almost spherical, amorphous formulation. The sustained release (following Higuchi kinetics) of drug from NT was observed. The mean systolic blood pressure of NT treated rats were found to be significantly reduced (*p < 0.01) to normal range up to 48 h and the plasma NIC concentrations were found to be maintained up to 36 h with enhanced bioavailability in comparison to pure drug suspension. The enhanced NIC exposure of NT (AUC0-α: 156.1 ± 13.7) compared to pure NIC suspension (AUC0-α: 89.7 ± 8.1) demonstrated the potentiality of NIC SNET for hypertension treatment.
Graphical AbstractNicardipine hydrochloride loaded oral self-nanoemulsifying system