Patent EA-000938-B1 (EA)
Title: Oral 2-methylthienobenzodiazepine formulation and process for making such formulation
Inventor: COCHRAN GEORGE R
IPC: A61K9/36
Filed: 1996-03-22
Abstract: 1. A solid oral formulation comprising olanzapine as an active ingredient intimately mixed with a filler, binder, disintegrant, a dry binder to assure adequate friability, and a lubricant, wherein such solid oral formulation is coated with a polymer selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, dimethylaminoethyl and methacrylatemethyl acrylic acid ester copolymer, ethylacrylate and methylmethacrylate copolymer, methylcellulose and ethylcellulose. 2. A formulation as claimed in claim 1 wherein the polymer coat is selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose and ethylcellulose. 3. A formulation as claimed in claim 2 wherein the polymer coat is hydroxypropylmethyl cellulose.  4. A formulation as claimed in any one of claims 1-3 wherein the polymer coat is free of propyleneglycol.  5. A formulation as claimed in claim 4 wherein the filler is lactose. 6. A formulation as claimed in claim 4 wherein the binder is hydroxypropylcellulose and the disintegrant is crospovidone.  7. A formulation as claimed in claim 1 wherein the dry binder is microcrystalline cellulose. 8. A formulation as claimed in claim 1 wherein the lubricant is magnesium stearate.  9. A formulation as claimed in claim 1 wherein the hydroxypropylmethylcellulose is a subcoating which is further coated with a aqueous dispersion film coat.  10. A formulation as claimed in claim 9 wherein the solid formulation is imprinted using an edible ink.  11. A formulation as claimed in claim 9 wherein the formulation comprises from about 1 to about 3 % w/w olanzapine; from about 69.5 to about 87.5 % w/w lactose; from about 3.5 to about 4.5 % w/w hydroxypropylcellulose; from about 4 to about 6 % w/w crospovidone; from about 9 to about 11 % w/w microcrystalline cellulose; and from about 0.25 to about 1 % magnesium stearate.  12. A formulation as claimed in claim 1 wherein the solid formulation is a tablet.  13. A formulation as claimed in claim 12 wherein each tablet provides a dose of olanzapine selected from the group consisting of 1, 2.5, 5, 7.5, 10, 15 and 20 mg. 14. A formulation as claimed in claim 1 wherein olanzapine is practically pure polymorph Form II having a typical x-ray powder diffraction pattern as represented by the following interplanar spacings: d ( angstrom ) 10.2689 8.577 7.4721 7.125 6.1459 6.071 5.4849 5.2181 5.1251 4.9874 4.7665 4.7158 4.4787 4.3307 4.2294 4.141 3.9873 3.7206 3.5645 3.5366 3.3828 3.2516 3.134 3.0848 3.0638 3.0111 2.8739 2.8102 2.7217 2.6432 2.6007 15. A process for preparing a stable solid oral formulation, containing olanzapine as an active ingredient and having a polymer coating selected from the group consisting of hydroxypropyl methylcellulose, hydroxyethylcellulose, methylhydroxyethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, dimethylaminoethyl and methacrylatemethyl acrylic acid ester copolymer, ethylacrylate and methylmethacrylate copolymer, methylcellulose and ethylcellulose, comprising high shear aqueous wet granulation with fluid bed drying.  16. A process as claimed in claim 15 wherein olanzapine is practically pure polymorph Form II having a typical x-ray powder diffraction pattern as represented by the following interplanar spacings:  d ( angstrom ) 10.2689 8.577 7.4721 7.125 6.1459 6.071 5.4849 5.2181 5.1251 4.9874 4.7665 4.7158 4.4787 4.3307 4.2294 4.141 3.9873 3.7206 3.5645 3.5366 3.3828 3.2516 3.134 3.0848 3.0638 3.0111 2.8739 2.8102 2.7217 2.6432 2.6007 17. The use of solid formulation of olanzapine as claimed in claim 1 for treating conditions selected from the group consisting of psychosis, schizophrenia, a schizophriform disorder, mild anxiety and acute mania.  18. The use of solid formulation of olanzapine as claimed in claim 1 for treating of gastrointestinal disorder.