APREPITANT ORAL LIQUID FORMULATIONS
A liquid pharmaceutical compositions comprising Aprepitant is preferably prepared as an oral suspension dosage form for the prevention and control of acute and delayed chemotherapy induced nausea and vomiting, and/or for prevention of postoperative nausea and vomiting.
1 . A method of producing a stabilized aqueous suspension of aprepitant for oral administration, the method comprising:
combining a pharmaceutically effective amount of aprepitant particles, a cellulosic stabilizer, and an anionic surfactant with an acidic aqueous buffer to form a stabilized aqueous suspension;
wherein the aprepitant particles have an average particle size of less than 0.5 micron;
wherein the cellulosic stabilizer and the anionic surfactant are present in an amount effective that limits growth of the aprepitant particles in the stabilized aqueous suspension to equal or less than 20% within a month at ambient conditions; and
packaging the stabilized aqueous suspension in a form suitable for oral administration.
2 . The method of claim 1 wherein the aprepitant particles have an average particle size of less than 0.4 micron.
3 . The method of claim 1 wherein the aprepitant is present in the stabilized aqueous suspension in an amount of between 10.0 mg/g and 20.0 mg/g.
4 . The method of claim 1 wherein the acidic aqueous buffer has a pH of between 3.0 to 5.0.
5 . The method of claim 1 wherein the cellulosic stabilizer comprises a substituted cellulose, and wherein the cellulosic stabilizer is present in the stabilized aqueous suspension in an amount of between 2.0 mg/g and 10.0 mg/g.
6 . The method of claim 5 wherein the cellulosic stabilizer is hydroxypropyl methylcellulose.
7 . The method of claim 1 wherein the anionic surfactant is an alkylsulfate, and wherein the anionic surfactant is present in the stabilized aqueous suspension in an amount of between 0.5 mg/g and 5.0 mg/g.
8 . The method of claim 7 wherein the anionic surfactant is sodium dodecylsulfate.
9 . The method of claim 1 wherein the cellulosic stabilizer comprises a substituted cellulose that is present in the stabilized aqueous suspension in an amount of between 2.0 mg/g and 10.0 mg/g, and wherein the anionic surfactant is an alkylsulfate that is present in the stabilized aqueous suspension in an amount of between 0.5 mg/g and 5.0 mg/g.
10 . The method of claim 1 wherein the cellulosic stabilizer is hydroxypropyl methylcellulose and is present in the stabilized aqueous suspension in an amount of between 4.0 mg/g and 8.0 mg/g, and wherein the anionic surfactant is sodium dodecylsulfate and is present in the stabilized aqueous suspension in an amount of between 1.0 mg/g and 4.0 mg/g.
11 . A stabilized aqueous suspension of aprepitant for oral administration, comprising:
a pharmaceutically effective amount of aprepitant particles, wherein the aprepitant has an average particle size of less than 0.5 micron;
a cellulosic stabilizer and an anionic surfactant in an amount effective that limits growth of the aprepitant particles to equal or less than 20% within a month at ambient conditions;
an acidic aqueous buffer, and wherein the aqueous suspension of aprepitant is formulated for oral administration.
12 . The stabilized aqueous suspension of claim 11 wherein the aprepitant is present in the stabilized aqueous suspension in an amount of between 10.0 mg/g and 20.0 mg/g
13 . The stabilized aqueous suspension of claim 11 wherein the acidic aqueous buffer is a citrate buffer.
14 . The stabilized aqueous suspension of claim 11 packaged in a single use container containing between 5 and 15 ml of the stabilized aqueous suspension.
15 . The stabilized aqueous suspension of claim 11 wherein the cellulosic stabilizer comprises a substituted cellulose, and wherein the cellulosic stabilizer is present in the stabilized aqueous suspension in an amount of between 2.0 mg/g and 10.0 mg/g.
16 . The stabilized aqueous suspension of claim 15 wherein the cellulosic stabilizer is hydroxypropyl methylcellulose.
17 . The stabilized aqueous suspension of claim 11 wherein the anionic surfactant is an alkylsulfate, and wherein the anionic surfactant is present in the stabilized aqueous suspension in an amount of between 0.5 mg/g and 5.0 mg/g.
18 . The stabilized aqueous suspension of claim 17 wherein the anionic surfactant is sodium dodecylsulfate.
19 . The stabilized aqueous suspension of claim 11 wherein the cellulosic stabilizer comprises a substituted cellulose that is present in the stabilized aqueous suspension in an amount of between 2.0 mg/g and 10.0 mg/g, and wherein the anionic surfactant is an alkylsulfate that is present in the stabilized aqueous suspension in an amount of between 0.5 mg/g and 5.0 mg/g.
20 . The stabilized aqueous suspension of claim 11 wherein the cellulosic stabilizer is hydroxypropyl methylcellulose and is present in the stabilized aqueous suspension in an amount of between 4.0 mg/g and 8.0 mg/g, and wherein the anionic surfactant is sodium dodecylsulfate and is present in the stabilized aqueous suspension in an amount of between 1.0 mg/g and 4.0 mg/g.