Purpose: Berberine (BER) is a quaternary isoquinoline alkaloid possesses multitude of biological effects, including antiinflammatory, antidiabetic, lipid peroxidation, and neuroprotective activity and antihyperlipidemic. However, poor aqueous solubility and P-gp-mediated efflux limits its absorption in gastrointestinal tract and sub therapeutic plasma concentration (< 5%). The objective of present study was to develop and optimize self-nanoemulsifying systems (SNES) of berberine (BER) using design of experiments (DoE) approach. In addition, the present work also aimed to enhance oral bioavailability of BER for antihyperlipidemic activity
Methods: Based on solubility study, pseudo-ternary phase diagrams were constructed and SNES were optimized for oil, surfactant and co-surfactant. The formulation of BER loaded SNES was optimized by a simplex lattice experiment design. The formulations were characterized for various in vitro physicochemical characteristics. In vivo efficacy was evaluated in high fat diet induced hyperlipidemic rats.
Results: The optimal formulation of SNES was comprised of 45% surfactant (Tween 80), 45% co-surfactant (PEG 400) and 10% oil (Capmul MCM C8). The average particle size of SNES containing BER was about 20.54 nm when diluted in water. Dissolution studies revealed remarkable increase in dissolution of the drug as compared to plain drug. Furthermore, in vivo evaluation of formulations provided significant reduction in the total cholesterol levels in hyperlipidemic rats with reference to rats of control group (p<0.05).
Conclusion: These data suggest that simplex centroid design could be effectively used in optimization of SNES. In conclusion, this work could be a contribution towards the enhancement of bioavailability of BER used in treatment of hyperlipidemia.
Vinodkumar Ramani– Assistant Professor, firstname.lastname@example.org, Surat, Gujarat
Avinash Seth– HOD, Department of Pharmacy, Sumandeep Vidyapeeth, Vadodara
R Balaraman– Professor, Department of Pharmacy, Sumandeep Vidyapeeth
Ghanshyam Parmar– Assistant Professor, Sumandeep Vidyapeeth, Vadodara, Gujarat