Design, Fabrication and Characterization of Esomeprazole Nanocrystals for Enhancing the Dissolution Rate and Stability

Abstract

Background: Poor solubility and low dissolution rate limit the work at poorly water-soluble drugs like Esomeprazole. To overcome this problem, different technologies had to be used but could not resolve the problem, significantly. The main aim of this patent study was to prepare the nanocrystals using the evaporative precipitation ultrasonication method in order to improve the dissolution rate and stability of Esomeprazole (ESM). Methods: For obtaining the nanocrystals, different nanoformulations were prepared using the pluronic F-68 in different concentrations, and then the screened formulation was lyophilized in the presence of two distinct cryoprotectants; mannitol and sucrose. The obtained nanocrystals were characterized for their re-dispersibility, crystalline state, dissolution behavior, particle size, polydispersibility index and morphology. Dissolution study of ESM nanocrystals was performed in a buffer solution of pH-7.4, and compared to that of bulk ESM sample and ESM/pluronic F-68 physical mixture. Results: Cryoprotectant containing nanocrystals exhibit the re-dispersion in water after the manual shaking. 5% mannitol containing nanocrystals showed the least polydispersity index (0.42 ± 0.11) and narrowest particle size (186 ± 12.9 nm). The Powder X-ray Diffraction (PXRD) pattern and differential scanning calorimeter (DSC) thermograms revealed that the crystalline state of the drug was not changed after the different physical treatment. Freeze-dried nanocrystals showed a faster dissolution rate and almost 99.45% of the drug was released within 60 min. However, the bulk drug and a physical mixture of bulk drug/pluronic F-68 showed only 22.65% and 21.3% of drug release, respectively, after 60 min. This paper reviews the related patents on Esomeprazole Nanocrystals. Conclusion: The different findings revealed that nanocrystals could be a potential alternate for solving the dissolution rate and stability issue of ESM like poorly soluble drugs.