Crystalline form of lorlatinib free base

1. A solid dosage form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(m etheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile (lorlatinib) free base (Form 7), wherein the dosage form has a powder X-ray diffraction (PXRD) pattern comprising peaks at 2θ values of: 9.6, 10.1 and 16.2 °2θ±0.2 °2θ.

2. The dosage form of claim 1 , wherein the dosage form is a tablet, wherein the tablet comprises a tablet core.

3. The tablet of claim 2 , wherein the tablet core is 1-30% of lorlatinib free base (Form 7) on a w/w basis.

4. The tablet of claim 3 , wherein the tablet core is about 10% of lorlatinib free base (Form 7) on a w/w basis.

5. The tablet of claim 3 , wherein the tablet core is about 15% of lorlatinib free base (Form 7) on a w/w basis.

6. The tablet of claim 2 , wherein the tablet core further comprises a filler.

7. The tablet of claim 6 , wherein the filler is microcrystalline cellulose, dibasic calcium phosphate anhydrous, lactose monohydrate, or a combination thereof.

8. The tablet of claim 7 , wherein the filler is microcrystalline cellulose.

9. The tablet of claim 8 , wherein the tablet core is 35-60% microcrystalline cellulose on a w/w basis.

10. The tablet of claim 9 , wherein the tablet core is about 53% microcrystalline cellulose on a w/w basis.

11. The tablet of claim 9 , wherein the tablet core is about 58% microcrystalline cellulose on a w/w basis.

12. The tablet of claim 7 , wherein the filler is dibasic calcium phosphate anhydrous.

13. The tablet of claim 12 , wherein the tablet core is 10-35% dibasic calcium phosphate anhydrous on a w/w basis.

14. The tablet of claim 13 , wherein the tablet core is about 29% dibasic calcium phosphate anhydrous on a w/w basis.

15. The tablet of claim 13 , wherein the tablet core is about 27% dibasic calcium phosphate anhydrous on a w/w basis.

16. The tablet of claim 7 , wherein the filler is lactose monohydrate.

17. The tablet of claim 16 , wherein the tablet core is 35% lactose monohydrate on a w/w basis.

18. The tablet of claim 2 , wherein the tablet core further comprises a disintegrant.

19. The tablet of claim 18 , wherein the disintegrant is starch, alginic acid, silicates, or a combination thereof.

20. The tablet of claim 19 , wherein the starch is sodium starch glycolate.

21. The tablet of claim 20 , wherein the tablet core is 2-5% sodium starch glycolate on a w/w basis.

22. The tablet of claim 21 , wherein the tablet core is about 3% sodium starch glycolate on a w/w basis.

23. The tablet of claim 2 , wherein the tablet core further comprises a lubricant.

24. The tablet of claim 23 , wherein the lubricant is magnesium stearate, sodium lauryl sulfate, talc, or a combination thereof.

25. The tablet of claim 24 , wherein the lubricant is magnesium stearate.

26. The tablet of claim 25 , wherein the tablet core is 0.5-2.5% magnesium stearate on a w/w basis.

27. The tablet of claim 26 , wherein the tablet core is about 1% magnesium stearate on a w/w basis.

28. The tablet of claim 26 , wherein the tablet core is about 2% magnesium stearate on a w/w basis.

29. The tablet of claim 2 , wherein the tablet further comprises a film coating having a film coating weight.

30. The tablet of claim 29 , wherein the film coating is Opadry II Tan or Opadry II Lavender.

31. The tablet of claim 29 , wherein the film coating weight is about 3% on a w/w basis of the tablet core weight.

32. The tablet of claim 2 , wherein the tablet comprises about 25 mg or about 50 mg or about 100 mg (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile (lorlatinib) free base (Form 7).

33. The tablet of claim 2 , wherein the tablet consists of: 25 mg (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile (lorlatinib) free base; 143.325 mg microcrystalline cellulose; 71.675 mg dibasic calcium phosphate anhydrous; 7.500 mg sodium starch glycolate; 2.500 mg magnesium stearate; and 7.500 mg Opadry II Tan.

34. The tablet of claim 2 , wherein the tablet consists of: 50 mg (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile (lorlatinib) free base; 286.650 mg microcrystalline cellulose; 143.350 mg dibasic calcium phosphate anhydrous; 15.000 mg sodium starch glycolate; 5.000 mg magnesium stearate; and 15.000 mg Opadry II Lavender.

35. The tablet of claim 2 , wherein the tablet consists of: 100 mg (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile (lorlatinib) free base; 355.540 mg microcrystalline cellulose; 177.800 mg dibasic calcium phosphate anhydrous; 20.000 mg sodium starch glycolate; 13.330 mg magnesium stearate; and 20.000 mg Opadry II Lavender.

36. A tablet comprising 1-30% of lorlatinib free base (Form 7), 35-60% microcrystalline cellulose; 10-35% dibasic calcium phosphate anhydrous; 2-5% sodium starch glycolate; and 0.5-2.5% magnesium stearate; on a w/w basis, wherein the tablet has a powder X-ray diffraction (PXRD) pattern comprising peaks at 2θ values of: 9.6, 10.1 and 16.2 °2θ±0.2 °2θ.

37. A tablet comprising 1-30% of lorlatinib free base (Form 7), 35-60% microcrystalline cellulose; 10-35% lactose monohydrate; 2-5% sodium starch glycolate; and 0.5-1.5% magnesium stearate; on a w/w basis, wherein the tablet has a powder X-ray diffraction (PXRD) pattern comprising peaks at 2θ values of: 9.6, 10.1 and 16.2 °2θ±0.2 °2θ.