An oil-free microemulsion for intravenous delivery of diallyl trisulfide: formulation and evaluation.
The aim of the present study was to develop an oil-free o/w microemulsion, Cremophor EL:ethanol-propylene glycol:saline, for diallyl trisulfide (DATS) for intravenous (i.v.) administration to modify the safety and pharmacokinetics of DATS. The ternary diagram was constructed to identify the regions of dilutable microemulsions, and the optimal composition of microemulsion was determined by evaluation of injection safety such as hemolysis, intravenous stimulation and injection anaphylaxis compared to commercial formulation Chentian(®). Promising microemulsion with modified injection safety was developed that could incorporate 100 mg/g of DATS. The droplet size of the microemulsion was about 26 nm in diameter with narrow distribution (polydispersity index: 0.14). Acute toxicity test showed that median lethal dose (LD(50)) of DATS microemulsion was 1.69-fold higher than that of Chentian(®). Pharmacokinetics was assessed by comparing with the commercial injection after intravenous administration to rats at a dose of 30 mg/kg. The developed microemulsion showed significant higher area under the drug concentration-time curve and lower clearance and distribution volume than those of Chentian(®) (p<0.05). This helped DATS to reach higher level in vessel, and circulate in the blood stream for a longer time resulting in better therapeutic effect. In conclusion, microemulsion would be a promising intravenous delivery system for DATS.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100191, China.
Xinru
X
Li
Yuanting
Y
Yue
Yanxia
Y
Zhou
Yating
Y
Fan
Chao
C
Fan
Yanqing
Y
Huang
Fei
F
Wu
Yan
Y
Liu
D000498:Allyl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D019540:Area Under Curve; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010316:Particle Size; D019946:Propylene Glycol / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000737:chemistry; D013440:Sulfides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D013997:Time Factors; D014018:Tissue Distribution
D000498:Allyl Compounds; D000975:Antioxidants; D004655:Emulsions; D005079:Excipients; D013440:Sulfides; C042577:diallyl trisulfide; D000431:Ethanol; D012965:Sodium Chloride; C000515:cremophor EL; D019946:Propylene Glycol; D005990:Glycerol