| 摘要 |
Provided herein are drug delivery systems, such as self-nanoemulsifying drug delivery systems, self-emulsifying drug delivery systems and parenteral microemulsion formulations, suitable for parenteral or oral delivery to a subject. The drug delivery systems may comprise a benzimidazole derivative, e.g., mebendazole, an oil, a surfactant, a cosurfactant and a dipolar aprotic solvent in a microemulsion formulation. Also provided are methods for improving the bioavailability of a benzimidazole derivative during treatment of a pathophysiological condition by using a formulation combining a particular emulsion droplet diameter and ratio of the surfactant:cosurfactant therein, for increasing concentration and retention of a benzimidazole derivative in the lung via a parenterally administerable microemulsion with droplet size of about 35 nm to less than 100 nm and for defining hemolytically safe microemulsions of a benzimidazole derivative during a therapeutic treatment via a parenterally administerable microemulsion with a surfactant:cosurfactant content by weight of about 6% to 48%. |
| 主权项 |
1. A drug delivery composition, comprising:
a) a benzimidazole derivative having the formula:wherein R3 is selected from the group consisting of H, carboxyl (—CO2H), hydroxyl, amino, chloro, difluormethoxy, benzoyl, phenyl-thio, pyridinyl, propyl-thio, diphenyl, 5-methoxy, fluorophenylmethyl-2-chloro, propenyl, chloropropyl or esters (—CO2R4) wherein R4 is selected from the group consisting of alkoxy, haloalkyl, alkenyl, and cycloalkyl, wherein the alkyl groups have from 1-8 carbons, or CH3CH2(OCH2CH2)n-, or CH3CH2CH2(OCH2CH2CH2)n-, or (CH3)2CH(OCH(CH3)CH2)n-, wherein n is from 1-3 wherein R1 is OH, Cl, SH, carbamate or piperidin-4-yl, and R2 is hydrogen, α-methylvinyl, 3-chloropropyl or piperidin-4-yl, or the pharmaceutically effective organic or inorganic salts thereof, or mixtures thereof;
b) an oil; c) a surfactant; d) a cosurfactant; and e) a dipolar aprotic solvent, wherein said delivery composition forms as a parenterally-deliverable microemulsion having a droplet diameter of about 478 nm to less than 500 nm. |
