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. A solid tablet for oral administration comprising:
80 mg, 160 mg, or 320 mg micronized zanubrutinib in crystal form A;
a filler comprising lactose in an amount of about 20% to about 70% by mass of the solid tablet; and
a glidant in an amount from about 0.1% to about 20% by mass of the solid tablet, wherein the glidant is powdered cellulose, magnesium trisilicate, colloidal silica, talc powder, or any combination thereof,
provided that if the solid tablet contains lactose as the only filler in the solid tablet, the amount of lactose in the solid tablet is not less than that of zanubrutinib,
wherein at least about 80% of zanubrutinib is dissolved within 60 minutes in a solution having a pH value of about 1.2 and comprising sodium lauryl sulfate in an amount of about 0.5% by mass of the solution at a temperature of 37±0.5° C. with a rotating speed of 100 rpm.
2. The solid tablet of claim 1 , further comprising a binder, a disintegrant, a wetting agent, a lubricant, or any combination thereof.
3. The solid tablet of claim 1 , wherein the filler further comprises starch, sucrose, microcrystalline cellulose, mannitol, pregelatinized starch, glucose, maltodextrin, cyclodextrin, cellulose, silicified microcrystalline cellulose, or any combination thereof.
4. The solid tablet of claim 1 , further comprising microcrystalline cellulose in an amount of about 10% to about 50% by mass of the solid tablet.
5. The solid tablet of claim 1 , further comprising
microcrystalline cellulose in an amount of less than about 50% by mass of the solid tablet.
6. The solid tablet of claim 2 , wherein the binder is starch, hypromellose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, gelatin, sucrose, or any combination thereof.
7. The solid tablet of claim 1 , further comprising polyvinylpyrrolidone in an amount of less than about 10% by mass of the solid tablet.
8. The solid tablet of claim 2 , wherein the disintegrant is sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, croscarmellose, methyl cellulose, pregelatinized starch, sodium alginate, or any combination thereof.
9. The solid tablet of claim 1 , further comprising croscarmellose sodium in an amount of about 0.5% to about 5% by mass of the solid tablet.
10. The solid tablet of claim 1 , further comprising sodium lauryl sulfate in an amount of about 0.5% to about 5% by mass of the solid tablet.
11. The solid tablet of claim 1 , wherein the glidant is colloidal silica.
12. The solid tablet of claim 2 , wherein the lubricant is zinc stearate, glyceryl monostearate, glyceryl palmitate stearate, magnesium stearate, sodium fumarate stearate, or any combination thereof.
13. The solid tablet of claim 1 , further comprising magnesium stearate in an amount of about 0.1% to about 2% by mass of the solid tablet.
14. The solid tablet of claim 1 , further comprising a film coating powder, polyvinyl alcohol, hydroxypropyl cellulose, polyethylene glycol, or any combination thereof.
15. The solid tablet of claim 1 , comprising:
80 mg, 160 mg, or 320 mg micronized zanubrutinib in crystal form A;
colloidal silica in an amount of about 0.88% to about 12% by mass of the solid tablet;
lactose in an amount of about 40% to about 60% by mass of the solid tablet;
microcrystalline cellulose in an amount of about 4% to about 10% by mass of the solid tablet;
polyvinylpyrrolidone in an amount of less than about 5% by mass of the solid tablet;
croscarmellose sodium in an amount of about 0.5% to about 5% by mass of the solid tablet;
sodium lauryl sulfate in an amount of about 0.5% to about 1.0% by mass of the solid tablet; and
magnesium stearate in an amount of about 0.3% to about 1% by mass of the solid tablet.
16. The solid tablet of claim 1 , comprising:
80 mg, 160 mg, or 320 mg micronized zanubrutinib in crystal form A;
colloidal silica in an amount of about 0.88% to about 12% by mass of the solid tablet;
lactose in an amount of about 40% to about 60% by mass of the solid tablet;
polyvinylpyrrolidone in an amount of less than about 5% by mass of the solid tablet;
croscarmellose sodium in an amount of about 0.5% to about 5% by mass of the solid tablet;
sodium lauryl sulfate in an amount of about 0.5% to about 1.0% by mass of the solid tablet; and
magnesium stearate in an amount of about 0.3% to about 1% by mass of the solid tablet.
17. A solid tablet, comprising:
80 mg, 160 mg, or 320 mg micronized zanubrutinib in crystal form A;
colloidal silica in an amount of about 0.88% to about 12% by mass of the solid tablet;
microcrystalline cellulose in an amount of about 30% to about 50% by mass of the solid tablet;
polyvinylpyrrolidone in an amount less than about 5% by mass of the solid tablet;
croscarmellose sodium in an amount of about 0.5% to about 5% by mass of the solid tablet;
sodium lauryl sulfate in an amount of about 0.5% to about 1.0% by mass of the solid tablet; and
magnesium in an amount of about 0.3% to about 1% by mass of the solid tablet, wherein at least about 80% of zanubrutinib is dissolved within 60 minutes in a solution having a pH value of about 1.2 and comprising sodium lauryl sulfate in an amount of about 0.5% by mass of the solution at a temperature of 37±0.5° C. with a rotating speed of 100 rpm.
18. The solid tablet of claim 1 , wherein the micronized zanubrutinib has a particle size of no more than 40 μm.
19. The solid tablet of claim 1 comprising 160 mg zanubrutinib.
20. The solid tablet of claim 1 comprising 80 mg zanubrutinib.
21. The solid tablet of claim 1 comprising 320 mg zanubrutinib.
22. The solid tablet of claim 19 , comprising lactose in an amount of about 52% by mass of the solid tablet;
microcrystalline cellulose in an amount of about 10% by mass of the solid tablet;
polyvinylpyrrolidone in an amount of about 3% by mass of the solid tablet;
croscarmellose sodium in an amount of about 5% by mass of the solid tablet;
sodium lauryl sulfate in an amount of about 0.5% by mass of the solid tablet;
colloidal silica in an amount of about 2% by mass of the solid tablet; and
magnesium stearate in an amount of about 0.8% by mass of the solid tablet.
23. The solid tablet of claim 22 , wherein
more than about 90% of zanubrutinib is dissolved within about 30 minutes in a solution having a pH value of about 1.2 and comprising sodium lauryl sulfate in an amount of about 0.5% by mass of the solution at a temperature of 37±0.5° C. with a rotating speed of 100 rpm.