Enhanced oral bioavailability of fluvastatin by using nanosuspensions containing cyclodextrin

Abstract

BackgroundIn this study, fluvastatin (FVT) nanosuspensions containing cyclodextrin were developed to improve oral bioavailability.MethodsFVT nanosuspensions containing cyclodextrin were prepared by a high pressure homogenization technique. The nanosuspensions system was then characterized by transmission electron microscopy (TEM), particle size, differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). In addition, in vitro drug release properties, pharmacokinetics and pharmacodynamics were also investigated in detail.ResultsAfter lyophilization, the nanosuspensions could be redispersed gently and with a narrow particle size distribution, but the particle size has no obvious change. The powder X-ray diffraction and differential scanning calorimetry of FVT nanosuspensions showed that FVT existed in amorphous form in nanosuspensions. In vitro release, FVT nanosuspensions have sustained-release properties. Meanwhile, FVT nanosuspensions could significantly modify the pharmacokinetic profile and increase the bioavailability of FVT by more than 2.4-fold in comparison with the FVT capsules group. In vivo irritation test showed that there was almost no evidence of hemorrhagic mucosal erosion and intestinal villus destruction in rat gastric mucosa.ConclusionThe combination of nanocrystallization and cyclodextrin complexation techniques is a new attempt to formulate poorly water-soluble FVT.

Formulation and evaluation of fluvastatin sodium drug-in-adhesive transdermal system

“…Figure 6B which may be due to the dispersion of drug in molecular form in the adhesive and can also be attributed to the small amount of drug present in the formulation. Such behaviour is reported by Li J et al, 2018 in case of fluvastatin -β cyclodextrin nanosuspensions [19], Sharma P et al, 2017 for drug in matrix type of transdermal patch [20 ]. Figure 7A shows characteristic intense peaks between 2θ of 6 and 25, however in case of DIA patch the intensity of peaks were decreased indicating amorphous nature of drug [19] as seen in Figure 7B.…”

Emerging role of nanosuspensions in drug delivery systems

“…Pharmacokinetic study demonstrated significant improvement in the oral bioavailability in rabbits by naringenin nanosuspension in comparison to naringenin solution [70]. Pharmacokinetic evaluation of fluvastatin nanosuspensions in rats showed 2.4 folds improvement in bioavailability in comparison to fluvastatin capsule control group [48]. Faster absorption from naproxen nanosuspension decreased time to reach maximum concentration (T max ) by nearly 50% and increased AUC to about 5 folds, when compared to conventional tablet and suspension [55].…”