Journal
DRUG DELIVERY
Volume 19, Issue 4, Pages 232-237Publisher
INFORMA HEALTHCARE
DOI: 10.3109/10717544.2012.690109
Keywords
Indomethacin; solidified polymeric micelles; poorly soluble drugs; in vitro dissolution; in vivo pharmacokinetic
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Funding
- Roche Pharmaceutical Company
- Ministry of Science and Technology of the People's Republic of China [2009ZX09310-004]
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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.
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