Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion.
To improve the bioavailability and photostability of poorly water-soluble and photosensitive amlodipine, dry emulsion (DE) was prepared by spray-drying the oil-in-water emulsion of amlodipine. Labrafil M 1944 CS and dextrin were employed as oil phase and matrix material, respectively. Dispersing DE in distilled water formed an emulsion with a mean droplet size 1.4-fold larger than that of the homogenized amlodipine emulsion before spray-drying (0.24 +/- 0.30 microm versus 0.17 +/- 0.02 microm). The mean droplet size of DE remained unchanged during 6-month storage at room temperature. 94.4% versus 33.1% of amlodipine remained intact after 24-h UV irradiation of amlodipine as DE formulation or as powder. These data suggest that DE formulation greatly improved the photostability of amlodipine, as well as increasing the physical stability of emulsion systems. In vitro release of DE was higher than that of amlodipine powder (66% versus 48% release at 60 min). Consequently, DE formulation resulted in 2.6- and 2.9-fold higher Cmax and AUC0-24 h of amlodipine compared after oral administration of amlodipine powder in rats. Our data suggest that the DE may be a potential oral dosage form for amlodipine to improve its bioavailability.
Jang
Dong-Jin
DJ
Laboratory of Excellency for Drug and Gene delivery, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Jeong
Eun Ju
EJ
Lee
Hwa-Mi
HM
Kim
Bae-Chan
BC
Lim
Soo-Jeong
SJ
Kim
Chong-Kook
CK
D017311:Amlodipine / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004655:Emulsions; D008297:Male; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations; D010777:Photochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D004655:Emulsions; D004364:Pharmaceutical Preparations; D017311:Amlodipine