Design Expert-implemented Nimodipine Nanoemulsion: Fabrication, Optimization, and Characterization for Improved Oral Bioavailability and Physical Stability

Abstract

Background The oral bioavailability and biological half-life (t1/2) of nimodipine(NIMO) are 13%(approximately) and 7-8h, respectively. The poor oral bioavailability and short t1/2 are due to extensive hepatic metabolism. Due to short t1/2, frequent drug administration is required, which leads to the patient being incompliant and inconvenient. In order to improve the oral bioavailability as well as the physical stability, quality by design(QbD)-driven NIMO nanoemulsion was developed with a certain quality target product profile (QTPP). .In this investigation, the three components triacetin as oil phase, labrasol as a surfactant, and plurol oleique CC 497 as co-surfactant were selected after screening. The ratio of surfactant and co-surfactant (Smix) was selected from the pseudo-ternary phase diagram drawn by using ProSim ternary software. A d-optimal mixture design was employed to optimize the formulation. The dynamic light scattering (DLS), FTIR, DSC, X-RD, SEM, in vitro drug release, stability study, and in vivo pharmacokinetic studies were carried out for the characterization of the optimized formulation. Results The globule size, PDI, and Zeta potential of the optimized formulation were found to be 322.1 nm, 0.48, and − 14.5 mV respectively. The result of in vivo pharmacokinetic studies exhibited three-fold enhanced oral bioavailability of the optimized nanoemulsion as compared to the pure drug of nimodipine and the physical stability of the optimized nanoemulsion improved significantly as compared to the pure drug. Conclusion The NIMO-loaded nanoemulsion can be successfully fabricated by implementing the QbD approach with improved oral bioavailability and physical stability significantly as compared to the pure drug of NIMO.