Process for the preparation of sterile ophthalmic aqueous fluticasone propionate form a nanocrystals suspensions

An ophthalmic aqueous nanosuspension administrable topically onto eyelids, eyelashes or eyelid margin consisting of:

• (a) 0.1% w/w fluticasone propionate Form A nanocrystals and a vehicle consisting of:
• (b) 0.50% w/w methylcellulose 4000 cp;
• (c) 0.2% w/w polysorbate 80;
• (d) 0.1% w/w edetate disodium dihydrate;
• (e) 1.0% w/w boric acid;
• (f) 0.9% w/w glycerol;
• (g) 0.01% w/w benzalkonium chloride;
• (h) 0.055% w/w sodium chloride;
• (i) hydrochloric acid 1N and/or sodium hydroxide 1N as adjusting agents in an amount sufficient to pH 7.3-7.5;
• and
• (j) water q.s. to 100% w/w,
• wherein said nanocrystals of fluticasone propionate Form A have a mean particle size from 100 nm to 1000 nm and a X-ray powder diffraction pattern comprising peaks at about 7.8, 15.7, 20.8, 23.7, 24.5, and 32.5 degrees 2⊖, further comprising peaks at about 9.9, 13.0, 14.6, 16.0, 16.9, 18.1, and 34.3 degrees 2⊖, and wherein the nanocrystals are nanoplates having a [001] crystallographic axis normal to a surfaces that define a thickness of the nanoplates, wherein said ophthalmic aqueous nanosuspension contains a boric acid/glycerol complex.