Preparation and evaluation of SEDDS and SMEDDS containing carvedilol.
A new self-emulsifying drug delivery system (SEDDS) and self-microemulsifying drug delivery system (SMEDDS) have been developed to increase the solubility, dissolution rate, and, ultimately, oral bioavailability of a poorly water soluble drug, carvedilol. Ternary phase diagrams were used to evaluate the self-emulsification and self-microemulsfication domains. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The minimum self-emulsification time was found at a Tween 80 content of 40%. The particle size distribution and zeta-potential were determined. Benzoic acid had a dual function, it improved the self-emulsification performance of SEDDS and SMEDDS in 0.1 N HCl and lead to a positively charged emulsion. The in vitro dissolution rate of carvedilol from SEDDS and SMEDDS was more than two-fold faster compared with that from tablets. The developed SEDDS formulations significantly improved the oral bioavailability of carvedilol significantly, and the relative oral bioavailability of SEDDS compared with commercially available tablets was 413%.
Wei
Lanlan
L
Department of Pharmaceutics, Shen Yang Pharmaceutical University, Shen Yang, P.R. China. weilanlanww@yahoo.com.cn
Sun
Peinan
P
Nie
Shufang
S
Pan
Weisan
W
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019817:Benzoic Acid; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005026:Ethylene Glycols; D010316:Particle Size; D011136:Polysorbates; D011412:Propanolamines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012995:Solubility; D012997:Solvents; D013501:Surface-Active Agents
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D004655:Emulsions; D005026:Ethylene Glycols; D011136:Polysorbates; D011412:Propanolamines; D012997:Solvents; D013501:Surface-Active Agents; D000077261:Carvedilol; D019817:Benzoic Acid; C010111:carbitol