Aims and Background: The objective of the study was to improve the bioavailability of
poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure
homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of
drug and polymer.
Methods: Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH.
The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous
suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study
and stability study.
Results: RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ±
15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles
in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited
decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant
improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by
1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored
at 5°C ± 3°C.
Conclusion: The outcomes of the study revealed significant enhancement in dissolution rate and oral
bioavailability of RPG due to size reduction to nano range by HPH.