Novel oral delivery system of indomethacin by solidified mPEG-PDLLA micelles: in vivo study.
To administer indomethacin (IND) orally using polymeric micelles, IND loaded solidified polymeric micelles (IND-SPM) were prepared and evaluated for their in vitro and in vivo characteristics. IND and methoxy-poly(ethylene glycol) poly(d, l-lactide) copolymer (mPEG-PDLLA) were dissolved in acetone followed by the addition of an equivalent amount of polyplasdone XL-10 and stirred to obtain a suspension. Afterwards, acetone was completely evaporated. It was found that IND-SPM generates small polymeric micelles of 18.1 nm. Moreover, the solubility of IND at pH 6.8 increased 4.6-folds, and more than 90% of IND in 20 mg of IND-SPM was dissolved in 250 mL SIF pH 6.8 within 30 min. Pharmacokinetic parameters in fasted rats showed that IND-SPM 1:3 resulted in 3-folds increase of AUC and C(max) compared to commercial IND. mPEG-PDLLA micelles were found to be efficient carriers for oral administration of IND as solid dosage forms by adsorption on polyplasdone XL-10.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Ammar
A
Ouahab
Yan
Y
Shen
Jia-sheng
JS
Tu
D000284:Administration, Oral; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol; D007213:Indomethacin