Preparation, optimization and preliminary pharmacokinetic study of curcumin encapsulated turmeric oil microemulsion in zebra fish

The present investigation aimed to develop curcumin loaded turmeric oil microemulsion for brain targeting. An effort has been made to investigate the role of functional components in developing brain targeted formulation which could enhance the bioavailability and uptake of drug in the brain upon oral administration. Preliminary studies like solubility study, emulsification study and construction of the pseudo ternary phase diagram were performed for screening components. The formulation was optimized by using extreme vertices mixture design. The optimized formulation was characterized for appearance, stability to centrifugation, dilution potential, globule size, zeta potential and drug content. Furthermore, ex-vivopermeation in chicken gut sac non everted technique and pharmacokinetic study in adult zebra fishes were carried out.

The optimized formulation was found to clear, yellow-colored with the absence of phase separation and precipitation denoted the stability of formulation to centrifugation and dilution. The mean globule size, polydispersity index, zeta potential and drug content was observed as 29.13± 0.12 nm, 0.23 ± 0.01,–12.33 ± 1.37 mV and 99.10±3.91 %, respectively. Ex vivo permeation study revealed 2.41 fold enhancement in the steady-state flux when compared to curcumin solution. Furthermore, optimized formulation showed shorter T_max (5 min) and higher AUC_(0-∞) (7.93 μg/brain*min) compared to the curcumin solution which showed similar T_max and AUC_(0-∞) of 2.78 μg/brain*min after oral administration to zebra fishes revealing 3.97 fold enhancement. The results revealed enhanced ex vivooral absorption and enhanced in vivo brain pharmacokinetics of curcumin via functional microemulsion in the zebra fish model.

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Keywords Turmeric oil, Minitab software, brain targeting, curcumin, oral delivery, Danio rerio, Transcutol P, Labrasol ALF, Soluphor P (Kollisolv® PYR), Kolliphor HS15, Kolliphor RH40

Suraj Kewal More, Atmaram Pandurang Pawar, Preparation, optimization and preliminary pharmacokinetic study of curcumin encapsulated turmeric oil microemulsion in zebra fish, European Journal of Pharmaceutical Sciences, Volume 155, 2020, 105539, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2020.105539.