Development and Characterization of a Self-Nanoemulsifying Drug Delivery System Comprised of Rice Bran Oil for Poorly Soluble Drugs
- 207 Downloads
Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets’ behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100 nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4 h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.
KEY WORDSrice bran oil SNEDDS poorly soluble drugs multifactor analysis simulated intestinal fluids
The current work has received financial support within the project “Sustainable techno-economic solutions for the agricultural value chain” Waste-7-2015 topic H2020 690142 project (AGROCYCLE). Gattefosse (France) and BASF (Germany) are greatly acknowledged for the generously gifted formulation excipients.
- 31.Irakli M, Kleisiaris F, Mygdalia A, Katsantonis D. Stabilization of rice bran and its effect on bioactive compounds content, antioxidant activity and storage stability during infrared radiation heating. J Cereal Sci. 2018;80:135–42.Google Scholar
- 39.Piriyaprasarth S, Juttulapa M, Sriamornsak P. Stability of rice bran oil-in-water emulsions stabilized by pectin–zein complexes: effect of composition and order of mixing. Food Hydrocoll. 2016;61:589–98.Google Scholar
- 41.Theodoropoulos D, Rova A, Smith JR, Barbu E, Calabrese G, Vizirianakis IS, et al. Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane. Bioorg Med Chem Lett. 2013;23(22):6161–6.PubMedGoogle Scholar
- 49.Gupta S, Chavhan S, Sawant KK. Self-nanoemulsifying drug delivery system for adefovir dipivoxil: design, characterization, in vitro and ex vivo evaluation. Colloids Surf Physicochem Eng Asp. 2011;392(1):145–55.Google Scholar