EP2968175A1

EP2968175A1 - Pharmaceutical compositions comprising imatinib

Info

Publication number: EP2968175A1
Application number: EP14727714.9A
Authority: EP
Inventors: Charalambos PATTIHIS; Antje NORDMANN; Panagiotis PANAGOPOULOS; Konstantinos-Emmanouil PANITSAS
Original assignee: Remedica Ltd; Pharmaceutical Oriented Services Ltd
Current assignee: Remedica Ltd; Pharmaceutical Oriented Services Ltd
Priority date: 2013-03-15
Filing date: 2014-03-04
Publication date: 2016-01-20
Also published as: WO2014139836A1; GB201304699D0

Abstract

The present invention is concerned with a solid oral dosage form comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said solid oral dosage form comprising said imatinib in an amount of greater than about 80% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.

Description

PHARMACEUTICAL COMPOSITIONS COMPRISING IMATINIB

The present invention is concerned with tablet and capsule compositions of imatinib, or a pharmaceutically acceptable salt thereof, and processes of preparing the same.

Imatinib is chemically designated as 4-[(4-methyl-l-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3- pyridinyl)-2-pyrimidinyl] amino]-phenyl] benzamide, and can be represented by the chemical structure of formula (I)

Imatinib is a protein tyrosine kinase inhibitor, especially useful in the treatment of various types of cancer. Specifically, the approved indications and patient groups for imatinib include adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment; adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis; adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy; adult patients with relapsed or refractory Ph+ ALL as monotherapy; adult patients with myelodysplastic / myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements; adult patients with advanced hypereosinophilic syndrome (HES) and / or chronic eosinophilic leukaemia (CEL) with FIPlLl-PDGFRa rearrangement; adult patients with Kit (CD 117) positive unresectable and / or metastatic malignant gastrointestinal stromal tumours (GIST); as adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST; adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and / or metastatic DFSP who are not eligible for surgery. Basic pharmaceutically active therapeutic compounds, such as imatinib, are commonly formulated into pharmaceutical preparations as an acid addition salt form, particularly as a crystalline acid addition salt. For example, imatinib is marketed in many countries as its monomethanesulfonate salt (imatinib mesylate) under the trademarks GLIVEC or GLEEVEC. Two crystal forms of imatinib mesylate are described in WO 99/03854. The crystal form designated as the beta form is described as having physical properties that make it advantageous for the manufacture of solid oral pharmaceutical dosage forms, such as tablet and capsule dosage forms.

The currently marketed formulations of imatinib mesylate are 100 mg and 400 mg film coated tablets. WO 03/090720 discloses tablets comprising imatinib mesylate which are prepared by means of wet granulation, and wherein imatinib, or a pharmaceutically acceptable salt thereof, is present in an amount of from about 30 to 80% (based on the free base) in weight based on the total weight of the tablet. WO 03/090720 explains that the inventors thereof encountered difficulties in the production of imatinib tablets due to high friability values and poor abrasion resistance. Further, the flexibility in the quantity of excipients, e.g. disintegrants, was found to be limited due to the high drug load of the product according to WO 03/090720.

There is a need for alternative imatinib compositions.

Accordingly, there is now provided by the present invention a solid oral dosage form comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said solid oral dosage form comprising said imatinib in an amount of greater than about 80% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form. I n particular, it is preferred that a solid dosage form according to the present invention comprises said imatinib in an amount of at least about 96%, or more preferably at least about 97%, or more preferably at least about 98%, or more preferably at least about 99%, or even up to 100%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said solid oral dosage form.

A solid oral dosage form according to the present invention can comprise either a tablet or a capsule, wherein preferred excipients for use therein, and associated formulation methods, are substantially as hereinafter described. Accordingly, in a first preferred embodiment of the present invention there is provided a tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutical ly acceptable excipients, said tablet comprising said imatinib in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet. In a second preferred embodiment of the present invention there is provided a capsule comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said capsule comprising said imatinib in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said capsule.

The one or more excipients as used in a solid oral dosage form according to the present invention preferably include pharmaceutically acceptable excipients, such as fillers, binders, disintegrants, glidants, lubricants and the like.

Suitable fillers for inclusion in solid oral dosage forms according to the present invention include sugars, sugar alcohols and polymeric glycosides. Examples of sugars are sucrose, glucose and lactose as the monohydrate or in anhydrous form. Examples of sugar alcohols include mannitol, xylitol and sorbitol. Examples of polymeric glycosides are maltodextrin, microcrystalline cellulose and starches of different origins. I n particular, a filler is included in an oral dosage form according to the present invention when imatinib is present as imatinib free base. In an alternative preferred embodiment, however, a solid dosage form according to the present invention can be essentially free from any excipient that functions in said dosage form as a filler, which typically facilitates the high drug loading of a dosage form according to the present invention.

Suitable binders for inclusion in solid oral dosage forms according to the present invention so as to ensure the required mechanical strength, include wet and / or dry binders depending on the formulation process employed. Typical binders include polymers, such as polyvinylpyrrolidone, and cellulose derivatives, such as hydroxypropyl cellulose and microcrystalline cellulose (which as indicated above can also function as a filler). A preferred wet binder comprises hydroxypropyl cellulose and a preferred dry binder comprises microcrystalline cellulose. The amount of binder present can vary depending on the formulation process employed. Typically, however, a binder is present in an amount of less than about 2%, or in an amount of less than about 1%, based on the weight thereof compared to the total weight of the solid oral dosage form. The binder can be included either in dry state (mixed with imatinib before granulation), or can be dissolved or suspended in a granulation liquid. In certain embodiments and depending on the formulation process employed, then the dry binder might be employed in an extra-granular phase. I n a preferred wet granulation process according to the present invention, hydroxypropyl cellulose is dispersed in a suitable solvent, such as water, and mixed with imatinib or a pharmaceutically acceptable salt thereof, typically imatinib mesylate as hereinafter discussed. In an alternative preferred embodiment, however, a solid dosage form according to the present invention can be essentially free from any excipient that functions in said dosage form as a binder, which typically facilitates the high drug loading of a dosage form according to the present invention.

Examples of suitable disintegrants for inclusion in solid oral dosage forms according to the present invention are crospovidone and croscarmellose, such as croscarmellose sodium, starches and modified starches, e.g. maize starch, in pregelatinized form or as sodium glycolate, and hydroxypropyl cellulose with a low degree of substitution (L-HPC). A preferred disintegrant is sodium starch glycolate (suitably present in an extra-granular phase as hereinafter described). Typically, a disintegrant is present in an amount of less than about 2%, or in an amount of less than about 1%, based on the weight thereof compared to the total weight of the solid oral dosage form. In an alternative preferred embodiment, however, a solid dosage form according to the present invention can be essentially free from any excipient that functions in said dosage form as a disintegrant, which again typically facilitates the high drug loading of a dosage form according to the present invention.

Examples of suitable glidants, include colloidal silicon dioxide, calcium silicates and talcum. Colloidal silicon dioxide is preferred and typically a glidant is present in an amount of less than about 0.5%, based on the weight thereof compared to the total weight of the solid oral dosage form . Preferably a glidant is present in an extra-granular phase of a solid oral dosage form according to the present invention.

Preferred lubricants include stearic acid or salts thereof, with a particularly preferred lubricant comprising magnesium stearate. Typically lubricant is present in an amount of less than about 1%, such as about 0.8%, about 0.6% or about 0.4%, based on the weight thereof compared to the total weight of the solid oral dosage form. Lubricant can be present in an amount of about 0.6%. Preferably a lubricant is present at least in an extra-granular phase of a solid oral dosage form according to the present invention. In a preferred dry granulation process according to the present invention, a portion of lubricant, such as magnesium stearate, is mixed with imatinib, or a pharmaceutically acceptable salt thereof, prior to granulation, and further lubricant is typically present in the extragranular phase. In this way, an oral dosage form according to the present invention can comprise, or be prepared from, granules comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more lubricants. Such granules are then typically mixed with one or more glidants, and / or one or more lubricants, prior to formulation into final dosage form.

In the case where a solid oral dosage form comprises a tablet substantially as hereinbefore described, the tablet can be coated or un-coated. In a preferred embodiment, the tablet comprises a film coated tablet. As referred to herein, "film coated tablet" means a tablet core provided with a film coating, including suitable coating excipients together with other auxiliaries, such as plasticizers, colorants and the like.

It is also noted that as referred to herein, "core" denotes both the intra- and extra-granular phase as compressed together in a typical tabletting process, and by "total weight" of a tablet in the context of the present invention is meant the weight of a tablet being the intra- and extra-granular phases and a coating thereon (if any). "Total weight" in the context of a capsule in the context of the present invention is meant the weight of the intra- and extra-granular phases and a coating thereon (if any), which are to be included in an appropriate capsule shell.

It is particularly preferred that imatinib as present in a solid oral dosage form according to the present invention is present as the mesylate salt, and furthermore it is still further preferred that imatinib mesylate is present as crystalline form alpha as characterized in WO 99/03854.

There is also provided by the present invention a process of preparing a solid oral dosage form, comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said process comprising contacting said imatinib with said one or more pharmaceutically acceptable excipients, so as to provide a solid oral dosage form comprising said imatinib in an amount of greater than about 80% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form. The above process can comprise a dry or wet granulation process, or direct compression.

In the case where the dosage form is a tablet, typically the process comprises initially forming an intra-granular phase comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more excipients, by dry granulation or wet granulation (such as wet mixing or spray granulating), blending with one or more excipients of an extra-granular phase, and compressing the resulting mixture to form a tablet, and optionally and if required providing a film coating on the compressed tablet. In an alternative embodiment, the process may involve slugging.

In a particular dry granulation process according to the present invention, imatinib or a pharmaceutically acceptable salt thereof, is mixed with one or more suitable lubricants, such as magnesium stearate, the resulting mixture is granulated, followed by mixing with one or more glidants and / or a second portion of one or more suitable lubricants.

If a wet granulation process is employed, then any suitable granulation liquid can be used, such as water, ethanol, isopropanol, or mixtures thereof.

In the case where the dosage form is a tablet, alternatively the process can typically comprise a direct compression process wherein imatinib (which can be compacted) is blended with excipients, the blend is compressed and where required provided with a film coating. In such a direct compression process, the excipients can typically consist essentially of a glidant and a lubricant, with a preferred glidant being colloidal silicon dioxide and a preferred lubricant being magnesium stearate. A direct compression technique can suitably facilitate particularly high drug loading of the imatinib, either as the free base or a pharmaceutically acceptable salt, preferably in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of the tablet.

In a particularly preferred process of the present invention, therefore, there is provided a process of preparing a tablet comprising imatinib either as the free base, or a pharmaceutically acceptable salt thereof (especially mesylate), which comprises blending said imatinib with excipients that consist of magnesium stearate and silicon dioxide (in other words, no other excipient being present for this blending step), subjecting the resulting blend to direct compression to form a tablet core, and where appropriate providing a coating (typically a film coating) on the thus compressed tablet core, wherein said imatinib is present in the tablet in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of the tablet.

In the case where the dosage form is a capsule, typically the process comprises initially forming an intra-granular phase comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more excipients, by a dry or wet granulation process, blending with one or more excipients of an extra-granular phase, and filling the resulting mixture into an appropriately sized capsule.

In a preferred embodiment of the present invention, there is provided a film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said tablet comprising said imatinib in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, together with at least one glidant and at least one lubricant. Preferably, the imatinib is present in an amount of at least about 97.5%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet. Preferably, the imatinib is present as imatinib mesylate. Preferably, the glidant comprises colloidal silicon dioxide. Preferably, the lubricant comprises magnesium stearate. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a filler. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a binder. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a disintegrant. Preferably, the tablet is prepared by direct compression.

In this way there is thus provided a film coated tablet comprising a core and a film coating on the core, wherein said core consists essentially of imatinib, or a pharmaceutically acceptable salt thereof (in particular mesylate), a glidant and a lubricant, wherein said imatinib is present in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, wherein said tablet is prepared by direct compression. Furthermore, this tablet can be prepared by a process comprising blending said imatinib with excipients that consist of a glidant and a lubricant (in other words, no other excipient being present for this blending step), subjecting the resulting blend to direct compression to form a tablet core, and providing a film coating on the thus compressed tablet core, wherein said imatinib is present in the tablet in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of the tablet. In the above film coated tablet, the glidant is preferably silicon dioxide and the lubricant is preferably magnesium stearate.

In an alternative embodiment of the present invention, there is provided a film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said tablet comprising said imatinib in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, together with at least one lubricant, at least one binder and at least one disintegrant. Preferably, the imatinib is present as imatinib mesylate. Preferably, the lubricant comprises magnesium stearate. Preferably, the binder comprises hydroxypropyl cellulose. Preferably, the disintegrant comprises sodium starch glycolate. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a filler. Preferably, the tablet is prepared by a wet granulation process.

In a still further alternative embodiment of the present invention, there is provided a film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said tablet comprising said imatinib in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, together with at least one glidant and at least one lubricant. Preferably, the imatinib is present as imatinib mesylate. Preferably, the glidant comprises colloidal silicon dioxide. Preferably, the lubricant comprises magnesium stearate. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a filler. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a binder. Preferably, the tablet is essentially free from any excipient that functions in the tablet as a disintegrant. Preferably, the tablet is prepared by a dry granulation process.

It will be further understood that compositions according to the present invention as described herein can be used in the treatment of conditions that can be alleviated by the administration of a protein tyrosine kinase inhibitor, such as imatinib or a pharmaceutically acceptable salt thereof, such as imatinib mesylate. I n particular, compositions according to the present invention as described herein are useful in the treatment of various types of cancer and especially for the treatment of the approved indications for imatinib substantially as hereinbefore described.

The following examples are provided to illustrate the invention and are not to be construed as limiting the scope of the invention in any manner.

Example 1: Wet granulation:

Hydroxypropyl cellulose was dispersed in water. Imatinib mesylate was wetted with the hydroxypropyl cellulose / water dispersion and mixed until granules were formed. The granules were dried in a tray-drying oven and passed through an appropriate sieve. The dried and sieved granules were mixed with the sodium starch glycolate and magnesium stearate. The mixture was compressed into tablets and the tablets were coated.

Example 2: Dry granulation:

Imatinib mesylate was compacted with half the total amount of magnesium stearate. The resulting flakes were passed through an appropriate sieve. The resulting granules were mixed with colloidal silicon dioxide and the remaining magnesium stearate. The mixture was compressed into tablets and the tablets were coated.

Claims

Claims:

1. A solid oral dosage form comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said solid oral dosage form comprising said imatinib in an amount of greater than about 80% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.

2. A dosage form according to claim 1, wherein said imatinib is present in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said solid oral dosage form.

3. A dosage form according to claim 2, wherein said imatinib is present in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said solid oral dosage form.

4. A dosage form according to claim 3, wherein said imatinib is present in an amount of at least about 98%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said solid oral dosage form.

5. A dosage form according to claim 4, wherein said imatinib is present in an amount of at least about 99%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said solid oral dosage form.

6. A dosage form according to any of claims 1 to 5, which is a tablet, preferably a film coated tablet.

7. A dosage form according to any of claims 1 to 5, which

8. A dosage form according to any of claims 1 to 7, which is essentially free from any excipient that functions in said dosage form as a filler.

9. A dosage form according to any of claims 1 to 8, which further comprises one or more binders.

10. A dosage form according to claim 9, wherein said binder comprises hydroxypropyl cellulose.

11. A dosage form according to claim 9 or 10, wherein said binder is present in an amount of less than about 2%, based on the weight thereof compared to the total weight of the solid oral dosage form.

12. A dosage form according to claim 11, wherein said binder is present in an amount of less than about 1%, based on the weight thereof compared to the total weight of the solid oral dosage form.

13. A dosage form according to any of claims 1 to 8, which is essentially free from any excipient that functions in said dosage form as a binder.

14. A dosage form according to any of claims 1 to 13, which further comprises one or more disintegrants.

15. A dosage form according to claim 14, wherein said disintegrant comprises sodium starch glycolate.

16. A dosage form according to claim 14 or 15, wherein said disintegrant is present in an amount of less than about 2%, based on the weight thereof compared to the total weight of the solid oral dosage form.

17. A dosage form according to claim 16, wherein said disintegrant is present in an amount of less than about 1%, based on the weight thereof compared to the total weight of the solid oral dosage form.

18. A dosage form according to any of claims 1 to 13, which is essentially free from any excipient that functions in said dosage form as a disintegrant.

19. A dosage form according to any of claims 1 to 18, which further comprises one or more glidants.

20. A dosage form according to claim 19, wherein said glidant comprises colloidal silicon dioxide.

21. A dosage form according to claim 19 or 20, wherein said glidant is present in an amount of less than about 0.5%, based on the weight thereof compared to the total weight of the solid oral dosage form.

22. A dosage form according to any of claims 1 to 21, which further comprises one or more lubricants.

23. A dosage form according to claim 22, wherein said lubricant comprises magnesium stearate.

24. A dosage form according to claim 22 or 23, wherein said lubricant is present in an amount of less than about 1%, based on the weight thereof compared to the total weight of the solid oral dosage form.

25. A dosage form according to claim 24, wherein said lubricant is present in an amount of less than about 0.8%, based on the weight thereof compared to the total weight of the solid oral dosage form.

26. A dosage form according to claim 25, wherein said lubricant is present in an amount of about, or less than about, 0.6%, based on the weight thereof compared to the total weight of the solid oral dosage form.

27. A dosage form according to claim 26, wherein said lubricant is present in an amount of less than about 0.4%, based on the weight thereof compared to the total weight of the solid oral dosage form.

28. A dosage form according to any of claims 1 to 27, wherein said imatinib comprises imatinib mesylate.

29. A film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, wherein said imatinib is present in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, together with at least one glidant and at least one lubricant.

30. A tablet according to claim 29, wherein said imatinib is present in an amount of at least about 97.5%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet.

31. A tablet according to claim 29 or 30, wherein said imatinib comprises imatinib mesylate.

32. A tablet according to any of claims 29 to 31, wherein said glidant comprises colloidal silicon dioxide.

33. A tablet according to any of claims 29 to 32, wherein said lubricant comprises magnesium stearate.

34. A tablet according to any of claims 29 to 33, which is essentially free from any excipient that functions in said tablet as a filler.

35. A tablet according to any of claims 29 to 34, which is essentially free from any excipient that functions in said tablet as a binder.

36. A tablet according to any of claims 29 to 35, which is essentially free from any excipient that functions in said tablet as a disintegrant.

37. A tablet according to any of claims 29 to 36, prepared by a direct compression process.

38. A film coated tablet comprising a core and a film coating on the core, wherein said core consists essentially of imatinib, or a pharmaceutically acceptable salt thereof, a glidant and a lubricant, wherein said imatinib is present in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, wherein said tablet is prepared by direct compression.

39. A tablet according to claim 38, wherein said imatinib comprises imatinib mesylate.

40. A tablet according to claim 38 or 39, wherein said glidant comprises colloidal silicon dioxide.

41. A tablet according to any of claims 38 to 40, wherein said lubricant comprises magnesium stearate.

42. A process of preparing a film coated tablet comprising blending imatinib, or a pharmaceutically acceptable salt thereof, with excipients that consist of a lubricant and a glidant, subjecting the resulting blend to direct compression to form a tablet core, and providing a film coating on the thus compressed tablet core, wherein said imatinib is present in the tablet in an amount of at least about 97%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of the tablet.

43. A process according to claim 42, wherein said imatinib comprises imatinib mesylate.

44. A process according to claim 42 or 43, wherein said glidant comprises colloidal silicon dioxide.

45. A process according to any of claims 42 to 44, wherein said lubricant comprises magnesium stearate.

46. A film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, wherein said imatinib is present in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, together with at least one lubricant, at least one binder and at least one disintegrant.

47. A tablet according to claim 46, wherein said imatinib comprises imatinib mesylate.

48. A tablet according to claim 46 or 47, wherein said lubricant comprises magnesium stearate.

49. A tablet according to any of claims 46 to 48, wherein said binder comprises hydroxypropyl cellulose.

50. A tablet according to any of claims 46 to 49, wherein said disintegrant comprises sodium starch glycolate.

51. A tablet according to any of claims 46 to 50, which is essentially free from any excipient that functions in said tablet as a filler.

52. A tablet according to any of claims 46 to 51, prepared by a wet granulation process.

53. A film coated tablet comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, wherein said imatinib is present in an amount of at least about 96%, either based on the weight of the free base of imatinib when imatinib is present as the free base, or based on the weight of a pharmaceutically acceptable salt of imatinib when imatinib is present as a pharmaceutically acceptable salt, compared to the total weight of said tablet, together with at least one glidant and at least one lubricant.

54. A tablet according to claim 53, wherein said imatinib comprises imatinib mesylate.

55. A tablet according to claim 53 or 54, wherein said glidant comprises colloidal silicon dioxide.

56. A tablet according to any of claims 53 to 55, wherein said lubricant comprises magnesium stearate.

57. A tablet according to any of claims 53 to 56, which is essentially free from any excipient that functions in said tablet as a filler.

58. A tablet according to any of claims 53 to 57, which is essentially free from any excipient that functions in said tablet as a binder.

59. A tablet according to any of claims 53 to 58, which is essentially free from any excipient that functions in said tablet as a disintegrant.

60. A tablet according to any of claims 53 to 59, which is prepared by a dry granulation process.

61. A process of preparing a solid oral dosage form, comprising imatinib, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients, said process comprising contacting said imatinib with said one or more pharmaceutically acceptable excipients, so as to provide a solid oral dosage form comprising said imatinib in an amount of greater than about 80% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.