Self-Nanoemulsifying Drug Delivery System of Coenzyme (Q10) with Improved Dissolution, Bioavailability, and Protective Efficiency on Liver Fibrosis.
The aim of our investigation is to develop and characterize self-nanoemulsifying drug delivery systems (SNEDDS) of CoQ10to improve its water solubility, dissolution rate, and bioavailability, and then evaluate its biochemical and physiological effect on liver cirrhosis in rats compared with CoQ10powder. SNEDDS are isotropic and thermodynamically stable mixture of oil, surfactant, co-surfactant, and drug that form an oil/water nanoemulsion when added to aqueous phases with soft agitation. Upon administration, self-nanoemulsifying system becomes in contact with gastrointestinal fluid and forms o/w nanoemulsion by the aid of gastrointestinal motility. When the nanoemulsion is formed in the gastrointestinal tract, it presents the drug in a solubilized form inside small nano-sized droplets that provide a large surface area for enhancing the drug release and absorption. Solubility of CoQ10in various oils, surfactants, and co-surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. CoQ10-loaded SNEDDS were prepared using isopropyl myristate as oil; Cremophor El, Labrasol, or Tween80 as surfactant; and Transcutol as co-surfactant. The amount of CoQ10in each vehicle was 3%. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, as well as ex vivo permeability. Pharmacokinetics and hepatoprotective efficiency of the optimized SNEDDS of CoQ10compared with CoQ10suspension were performed. Results showed that all optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was in the nanometric range (11.7-13.5 nm) with optimum polydispersity index values (0.2-0.21). All formulae showed negative zeta potential (-11.3 to -17.2), and maximum drug loading efficiency. One hundred percent of CoQ10was released from most formulae within 30 min. One hundred percent of CoQ10was permeated from all formulae through 10 h. The pharmacokinetic study in rabbits revealed a significant increase in bioavailability of CoQ10SNEDDS to 2.1-fold compared with CoQ10suspension after oral administration. Comparative effect of the optimized formulae on acute liver injury compared with CoQ10powder was also studied; it was found that all the liver biochemical markers as alanine transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total protein (TP), and albumin were significantly improved at p < 0.05. Also, histochemical and histopthological studies confirm the biochemical results. Our results suggest the potential use of SNEDDS to increase the solubility of liphophilic drug as poorly water-soluble CoQ10and improve its oral absorption, so it can be more efficient to improve liver damage compared to CoQ10powder. These results demonstrated that CoQ10SNEDDS inhibited thioacetamide (TAA)-induced liver fibrosis mainly through suppression of collagen production.
Department of Pharmaceutics, National Organization for Drug Control and Research, Giza, Egypt. Abeer_khattab75@yahoo.com.
Abeer
A
Khattab
Department of Physiology, National Organization for Drug Control and Research, Giza, Egypt.
Lobna
L
Hassanin
Department of Physiology, National Organization for Drug Control and Research, Giza, Egypt.
Nashwah
N
Zaki
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008297:Male; D011817:Rabbits; D051381:Rats; D012995:Solubility; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
D004655:Emulsions; D014451:Ubiquinone; C024989:coenzyme Q10
coenzyme Q10; induced liver injury; liver fibrosis; self-emulsifying system