ORAL SOLID TABLET COMPRISING BRUTON'S TYROSINE KINASE INHIBITOR AND PREPARATION METHOD THEREFOR
Provided are an oral solid tablet comprising (S)-7-[4-(1-acryloylpiperidine)]-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and preparation method therefor. The oral solid tablet has good drug release characteristics, features easy administration, quick and high-efficient release, no particular requirements on equipment, and a simple formulation preparation process, can ensure formulation stability and facilitate transportation and storage, and is suitable for large-scale production.
1 . An solid tablet for oral administration containing Zanubrutinib, comprising: (1) 20% to 70%, preferably 30% to 50% of Zanubrutinib, all in mass percentages; and (2) one or more pharmaceutically acceptable excipients.
2 . The solid tablet for oral administration according to claim 1 , wherein the Zanubrutinib is of a crystal form A, an amorphous form, or a mixture of a crystal form A and an amorphous form.
3 . The solid tablet for oral administration according to claim 1 or 2 , wherein the excipient is selected from a filler, a binder, a disintegrant, a wetting agent, a glidant, a lubricant, and any combination thereof.
4 . The solid tablet for oral administration according to claim 3 , wherein the filler is selected from starch, sucrose, microcrystalline cellulose, mannitol, lactose, pregelatinized starch, glucose, maltodextrin, cyclodextrin, cellulose, silicified microcrystalline cellulose, and any combination thereof.
5 . The solid tablet for oral administration according to claim 4 , wherein the filler is lactose, and the content of the lactose is 20% to 70%, preferably 40% to 60%, all in mass percentages.
6 . The solid tablet for oral administration according to claim 4 , wherein the filler is microcrystalline cellulose, and the content of the microcrystalline cellulose is 10% to 50%, preferably 30% to 50%, all in mass percentages.
7 . The solid tablet for oral administration according to claim 4 , wherein the filler is a combination of lactose and microcrystalline cellulose, and the contents of the lactose and the microcrystalline cellulose are 0% to 70% and 0% to 50%, preferably 40% to 60% and 4% to 10%, respectively, all in mass percentages.
8 . The solid tablet for oral administration according to claim 3 , wherein the binder is selected from starch, hypromellose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, gelatin, sucrose, and any combination thereof.
9 . The solid tablet for oral administration according to claim 8 , wherein the binder is hypromellose, and the content of the hypromellose is 0% to 10%, preferably 0% to 5%, all in mass percentages.
10 . The solid tablet for oral administration according to claim 3 , wherein the disintegrant is selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, croscarmellose, methyl cellulose, pre gelatinized starch, sodium alginate, and any combination thereof.
11 . The solid tablet for oral administration according to claim 10 , wherein the disintegrant is croscarmellose sodium, and the content of the croscarmellose sodium is 0.5% to 5%, preferably 1% to 3%, all in mass percentages.
12 . The solid tablet for oral administration according to claim 3 , wherein the wetting agent is sodium lauryl sulfate, and the content of the sodium lauryl sulfate is 0% to 5%, preferably 0.5% to 1.0%, all in mass percentages.
13 . The solid tablet for oral administration according to claim 3 , wherein the glidant is selected from powdered cellulose, magnesium trisilicate, colloidal silica, talc powder, and any combination thereof.
14 . The solid tablet for oral administration according to claim 13 , wherein the glidant is colloidal silica, and the content of the colloidal silica is 0.1% to 20%, preferably 4% to 8%, all in mass percentages.
15 . The solid tablet for oral administration according to claim 3 , wherein the lubricant is selected from zinc stearate, glyceryl monostearate, glyceryl palmitate stearate, magnesium stearate, sodium fumarate stearate, and any combination thereof.
16 . The solid tablet for oral administration according to claim 15 , wherein the lubricant is magnesium stearate, and the content of the magnesium stearate is 0.1% to 2%, preferably 0.3% to 1%, all in mass percentages.
17 . The solid tablet for oral administration according to any one of claims 1 to 16 , wherein the solid tablet for oral administration further comprises a coating agent selected from an Opadry film coating powder, polyvinyl alcohol, hydroxypropyl cellulose, polyethylene glycol, and any combination thereof, preferably an Opadry film coating powder.
18 . A method for preparing the solid tablet for oral administration according to any one of claims 1 to 17 , wherein the granulation method of the solid tablet for oral administration is selected from direct powder compression, dry granulation, and wet granulation, preferably wet granulation.
19 . A method for preparing the solid tablet for oral administration according to any one of claims 1 to 17 , comprising the following steps:
(1) mixing the zanubrutinib and one or more excipients;
(2) subjecting the mixture of the zanubrutinib and one or more excipients to wet granulation with purified water, or an organic reagent, or an aqueous solution or an organic solution containing a binder, followed by drying and sizing;
(3) optionally, mixing the sized granules with an additional excipient and compressing them into plain tablets;
(4) optionally, coating the plain tablets,
wherein, if step (3) is not performed, the sized granules obtained in step (2) are compressed into plain tablets.
20 . The method according to claim 19 , wherein the organic reagent in step (2) is selected from ethanol, acetone, and a combination thereof.
21 . The method according to claim 19 or 20 , wherein the additional excipient in step (3) is selected from a filler, a lubricant, a glidant, and any combination thereof.