Aqueous ophthalmic suspension of crystalline rebamipide

摘要

The invention provides an ophthalmic product containing rebamipide, which has a transparency enough to be agreeable feeling on using it and has neutral to weakly acidic pH not to injury of the keratoconjunctiva of a patient suffering from dry eye. An aqueous suspension of crystalline rebamipide which has an improved transparency is provided by adding an aqueous solution of rebamipide dissolved by a base such as sodium hydroxide or an aqueous solution of a salt of rebamipide to an aqueous acidic solution such as hydrochloric acid containing at least one of the compounds selected from water-soluble polymers and surfactants, and mixing them.

主权项

1. An aqueous suspension of crystalline rebamipide comprising (1) a water-soluable salt of rebamipide; (2) hydroxypropylmethyl cellulose (HPMC) or polyvinylpyrrolidone (PVP); (3) hydrochloric acid; and (4) water; wherein said suspension is prepared by:
(a) mixing an aqueous solution comprising a polymer selected from HPMC or PVP with hydrochloric acid and purified water to form a hydrochloric acid-HPMC/PVP solution; (b) dissolving rebamipide in an aqueous solution comprising NaOH to from a sodium hydroxide-rebamipide solution; (c) adding the sodium hydroxide-rebamipide solution of step (b) to the hydrochloric acid-HPMC/PVP solution step (a) to deposit crystalline rebamipide; (d) stirring the suspension of step (c) to complete the crystallization; and (e) adjusting the pH of the aqueous suspension of step (d) to 5-7 with sodium hydroxide; wherein the shape of crystalline rebamipide is a regular crystal having a long gage length of less than 1000 nm and a short gage length of less than 60 nm, provided that the ration between the long gage length and short gage length is not less than 4.