Lurasidone solid dispersion and preparation method thereof
A lurasidone solid dispersion and a preparation method thereof. The solid dispersion includes a mixture of lurasidone, a pharmaceutical carrier and a plasticizer, in which the lurasidone is in a free base form. The lurasidone solid dispersion obtained by the preparation method has characteristics of high dissolution rate (over 30%) in partial neutral medium (such as pH 6.0), significantly increased bioavailability, and significantly reduced food effect, which overcomes the excessive medication limitation in the prior art, avoids the reduction or even inefficiency of the curative effect caused by improper medication of patients, ensures the normal exertion of the medication effect, thereby increases the flexibility and compliance of patients to take medicine.
1 . A lurasidone solid dispersion consisting of:
lurasidone in a free base form;
hydroxypropyl methylcellulose succinate acetate; and
stearic acid; and
another carrier;
wherein:
the another carrier is copovidone or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer;
the lurasidone and the hydroxypropyl methylcellulose succinate acetate have a weight ratio ranging from about 1:1 to about 1:4;
the lurasidone and the another carrier have a weight ratio ranging from about 1:1 to about 1:4; and
the lurasidone and the stearic acid have a weight ratio ranging from about 1:0.1 to about 1:0.42.
2 . The lurasidone solid dispersion of claim 1 , wherein the lurasidone solid dispersion is prepared by a melting method.
3 . The lurasidone solid dispersion according to claim 1 , wherein the carrier component consists of:
hydroxypropyl methylcellulose succinate acetate; and
polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.
4 . The lurasidone solid dispersion according to claim 1 , wherein the carrier component consists of hydroxypropyl methylcellulose succinate acetate and copovidone.
5 . A method of preparing the lurasidone solid dispersion of claim 1 , the method comprising:
melting a mixture of the lurasidone, the carrier component and the stearic acid to obtain the lurasidone solid dispersion.
6 . The method of claim 5 , wherein the melting is carried out under a temperature from 80° C. to 200° C. and a screw speed from 30 to 1000 rpm.
7 . A pharmaceutical composition comprising:
the lurasidone solid dispersion of claim 1 ; and
optionally, a pharmaceutically acceptable excipient comprising at least one selected from:
a filler comprising at least one selected from lactose, starch, microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose, mannitol, dextrin, pre-gelatinized starch, corn starch, sorbitol, calcium sulfate, calcium hydrogen phosphorous and calcium carbonate;
a disintegrant comprising at least one selected from crospovidone, croscarmellose sodium, sodium carboxymethyl starch, dry starch, low-substituted hydroxypropyl cellulose, microcrystalline cellulose and modified corn starch;
a binder comprising at least one selected from starch, pre-gelatinized starch, sodium carboxymethylcellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropylmethylcellulose, sucrose, gelatin, polyvinylpyrrolidone, microcrystalline cellulose and copovidone;
a surfactant comprising at least one selected from sodium lauryl sulfate, quaternary ammonium compound, lecithin, fatty acid glycerides, sorbitan fatty acid ester and polysorbate;
a flavouring agent comprising at least one selected from sucrose, sucralose, acesulfame, aspartame, stevioside, saccharin sodium and cyclamate; and
a lubricant comprising at least one selected from magnesium stearate, micropowder silicagel, stearic acid, talcum, glyceryl behenate, hydrogenated vegetable oil, wax, mineral oil, sodium stearyl fumarate and polyethylene glycol;
wherein the pharmaceutical composition is optionally in a form of granule, tablet, capsule or enteric formulation.
8 . A combination used for treatment of a psychosis, the combination comprising:
a first active ingredient comprising lurasidone in a form of the lurasidone solid dispersion as defined in claim 1 ; and
a second active ingredient comprising a drug other than lurasidone that is used for treating a psychosis.
9 . The combination of claim 8 , wherein the psychosis is at least one of schizophrenia, bipolar depression and autism.
10 . A method of treating at least one of schizophrenia, bipolar depression and autism in a patient in need thereof, the method comprising:
administering an effective amount of the combination of claim 8 to the patient.
11 . A method of treating a psychosis in a patient in need thereof, the method comprising:
administering an effective amount of the combination of claim 8 to the patient.
12 . A lurasidone solid dispersion comprising:
lurasidone in a free base form;
a carrier component consisting of:
hydroxypropyl methylcellulose succinate acetate; and
at least one carrier selected from copovidone and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; and
a plasticizer comprising at least one selected from poloxamer, propanediol, stearic acid, polyethylene glycol, tocopherol polyethylene glycol succinate, caprylocaproyl macrogolglyceride, triethyl citrate, diethyl phthalate and glycerin monostearate,
wherein:
the lurasidone and the hydroxypropyl methylcellulose succinate acetate have a weight ratio ranging from about 1:1 to about 1:30;
the lurasidone and the at least one carrier other than hydroxypropyl methylcellulose succinate acetate have a weight ratio ranging from about 1:1 to about 1:30; and
the lurasidone and the plasticizer have a weight ratio ranging from about 1:0.1 to about 1:6.
13 . The lurasidone solid dispersion of claim 12 , wherein the lurasidone and the plasticizer have a weight ratio ranging from about 1:0.1 to about 1:1.62.
14 . The lurasidone solid dispersion according to claim 12 , wherein the carrier component consists of:
hydroxypropyl methylcellulose succinate acetate; and
polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.
15 . The lurasidone solid dispersion according to claim 12 , wherein the carrier component consists of hydroxypropyl methylcellulose succinate acetate and copovidone.
16 . A lurasidone solid dispersion comprising:
lurasidone in a free base form;
a carrier component consisting of:
hydroxypropyl methylcellulose succinate acetate; and
at least one carrier selected from copovidone and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; and
a plasticizer component comprising stearic acid,
wherein:
the lurasidone and the hydroxypropyl methylcellulose succinate acetate have a weight ratio ranging from about 1:1 to about 1:4;
the lurasidone and the at least one carrier other than hydroxypropyl methylcellulose succinate acetate have a weight ratio ranging from about 1:1 to about 1:4; and
the lurasidone and the plasticizer have a weight ratio ranging from about 1:0.1 to about 1:0.42.