Nanosuspension of a poorly soluble drug via microfluidization process
Provided are compositions and methods for preparation and administration of an oral nanosuspension of a poorly soluble drug with improved bioavailability. The method is optimized through microfluidization process with water soluble polymeric excipients in the absence of surfactants.
1. A method for preparing a nanosuspension of a poorly soluble drug with improved bioavailability, said method consists of:
a) a first step consisting of microfluidizing a dispersion of a poorly soluble drug in an aqueous polymeric excipient solution in the absence of surfactants to form a stable concentrated nanosuspension; and
b) a second step consisting of diluting the concentrated nanosuspension in the presence of dispersants, co-solvents or surfactants to form deagglomerated and particle size controlled nanoparticles.
2. The method of claim 1 , wherein the poorly water soluble drug is cyclopropyl-N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-3-oxoisoindoline-4-yl}carboxamide or (+)-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione}.
3. The method of claim 1 , wherein the nanosuspension is administered orally.
4. The method claim 1 , wherein the aqueous polymeric excipient is a low molecular weight excipient.
5. The method of claim 4 , wherein the low molecular weight excipient is HPMC E5.
6. The method of claim 1 , wherein a co-solvent is selected from the group consisting of transcutol, PEG 300-800, glycerol, and ethanol.
7. The method of claim 1 , wherein the surfactant is a non-ionic surfactant.
8. The method of claim 7 , wherein the non-ionic surfactant is vitamin E-D-alpha tocopheryl polyethylene glycol 1000 succinate (E-TPGS), Labrasol™ or Tween-20™.
9. The method of claim 1 , wherein the surfactant is a ionic surfactant.
10. The method of claim 9 , wherein the ionic surfactant is sodium dodecyl sulfate (SLS).