Yong Qu1, Shunda Mu1, Chengwu Song1, Guohua Zheng2. 1. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, People's Republic of China. 2. Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.
Abstract
OBJECTIVE: To prepare a self-microemulsifying drug delivery system (SMEDDS) to increase the solubility and oral bioavailability of chrysin. METHODS: The preparation conditions were determined using factor analysis method. Preliminarily screening was conducted using compatibility tests and pseudo-ternary phase diagram studies. The central composite design-response surface methodology was used to determine the maximum drug loading and optimize SMEDDS formation, as characterized by surface morphology, pH, diameter, polydispersity index (PDI), zeta potential, and phase type. In vitro release of chrysin-suspension and chrysin-SMEDDS was investigated using the bulk-equilibrium reverse dialysis bag technique. Short-term stability of chrysin-SMEDDS at high and low temperatures was assessed. Pharmacokinetic behaviors were evaluated after intragastric and intravenous administration to rats. RESULTS: The final optimal formulation was medium chain triglyceride:oleic acid:Cremophor RH40: Transcutol HP (w/w) (12%:12%:32%:44%), with a drug loading capacity of 5 mg/g. Diluted chrysin-SMEDDS was characterized as an oil-in-water type and spherical, with a diameter, pH, PDI, and zeta potential of 28.26 ± 0.83 nm, 5.60 ± 0.84, 0.18 ± 0.01, and -23.13 ± 0.95 mV, respectively. The release speed of chrysin-SMEDDS was significantly higher than that of chrysin-suspension, and the release process was not affected by the media pH. In vivo pharmacokinetic data revealed that the oral bioavailability of chrysin-SMEDDS was 2.7-fold higher than that of chrysin suspension, compared with the chrysin microemulsion. CONCLUSION: The optimal SMEDDS formulation increased the dissolution and oral bioavailability of chrysin and may be useful for investigating chrysin efficacy in animal disease models and toxicokinetic studies.
OBJECTIVE: To prepare a self-microemulsifying drug delivery system (SMEDDS) to increase the solubility and oral bioavailability of chrysin. METHODS: The preparation conditions were determined using factor analysis method. Preliminarily screening was conducted using compatibility tests and pseudo-ternary phase diagram studies. The central composite design-response surface methodology was used to determine the maximum drug loading and optimize SMEDDS formation, as characterized by surface morphology, pH, diameter, polydispersity index (PDI), zeta potential, and phase type. In vitro release of chrysin-suspension and chrysin-SMEDDS was investigated using the bulk-equilibrium reverse dialysis bag technique. Short-term stability of chrysin-SMEDDS at high and low temperatures was assessed. Pharmacokinetic behaviors were evaluated after intragastric and intravenous administration to rats. RESULTS: The final optimal formulation was medium chain triglyceride:oleic acid:Cremophor RH40: Transcutol HP (w/w) (12%:12%:32%:44%), with a drug loading capacity of 5 mg/g. Diluted chrysin-SMEDDS was characterized as an oil-in-water type and spherical, with a diameter, pH, PDI, and zeta potential of 28.26 ± 0.83 nm, 5.60 ± 0.84, 0.18 ± 0.01, and -23.13 ± 0.95 mV, respectively. The release speed of chrysin-SMEDDS was significantly higher than that of chrysin-suspension, and the release process was not affected by the media pH. In vivo pharmacokinetic data revealed that the oral bioavailability of chrysin-SMEDDS was 2.7-fold higher than that of chrysin suspension, compared with the chrysin microemulsion. CONCLUSION: The optimal SMEDDS formulation increased the dissolution and oral bioavailability of chrysin and may be useful for investigating chrysin efficacy in animal disease models and toxicokinetic studies.
Entities:
Keywords:
Self-microemulsifying drug delivery system; central composite design-response surface methodology; chrysin; oral bioavailability; pharmacokinetics