WO2013139826A1 - Pharmaceutical compositions comprising imatinib - Google Patents
Pharmaceutical compositions comprising imatinib Download PDFInfo
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- WO2013139826A1 WO2013139826A1 PCT/EP2013/055764 EP2013055764W WO2013139826A1 WO 2013139826 A1 WO2013139826 A1 WO 2013139826A1 EP 2013055764 W EP2013055764 W EP 2013055764W WO 2013139826 A1 WO2013139826 A1 WO 2013139826A1
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- imatinib
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- Imatinib is chemically designated as 4-[(4-methyl-l-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3- pyridinyl)-2-pyrimidinyl] aminoj-phenyl] benzamide, and can be represented by the chemical structure of formula (I)
- 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said capsule.
- Preferred % amounts for said imatinib are as previously described.
- a filler is included in an oral dosage form according to the present invention in an amount in the range of about 15.0 to 30.0%, based on the weight thereof compared to the total weight of the solid oral dosage form, more preferably in an amount in the range of about 15.0 to 25.0%, and even more preferably in an amount in the range of about 15.0 to 20.0%, based on the weight thereof compared to the total weight of the solid oral dosage form.
- such disintegrants are present in an amount in the range of about 19.0 to 22.0%, based on the weight thereof compared to the total weight of the solid oral dosage form, and typically where such % weights for disintegrants are provided herein then these are based on the total amount of disintegrant present both in intra- and extra-granular phases of a solid oral dosage form according to the present invention.
- suitable glidants include colloidal silicon dioxide, calcium silicates and talcum. Colloidal silicon dioxide is preferred and typically a glidant is present in an amount in the range of about 0.1 to 1.0%, based on the weight thereof compared to the total weight of the solid oral dosage form.
- a glidant is present in an extra-granular phase of a solid oral dosage form according to the present invention.
- a solid oral dosage form comprises a tablet substantially as hereinbefore described
- the tablet comprises a film coated tablet.
- film-coated tablet means a tablet core provided with a film coating
- a typical film coating employs hydroxypropyl methylcellulose (hypromellose) as a key constituent together with other auxiliaries, such as plasticizers, colorants and the like.
- 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.
- a protein tyrosine kinase inhibitor such as imatinib or a pharmaceutically acceptable salt thereof, such as imatinib mesylate.
- 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.
- Example 1 is provided to illustrate the invention and are not to be construed as limiting the scope of the invention in any manner.
- Example 1
- Hypromellose was dissolved in the granulation solvent and mixed until a clear solution was obtained.
- Imatinib mesylate, microcrystalline cellulose and croscarmellose sodium were mixed and subsequently granulated with the granulating solution, until granules were formed. 3. The wet granules were dried and sifted.
- Hypromellose was dissolved in the granulation solvent and mixed until a clear solution was obtained. 2. Imatinib mesylate, microcrystalline cellulose and croscarmellose sodium were mixed and subsequently granulated with the granulating solution, until granules were formed.
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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 in the range of about 27.0 to 29.0% 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] aminoj-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, therefore, for an improved imatinib composition, which balances the required dosage amount of imatinib with excipient amount, while allowing greater flexibility in excipient choice compared to the disclosure of WO 03/090720. In particular, when the worked Examples of WO 03/090720 are reviewed, then it can be seen that Example 1 describes a 100 mg tablet with a total tablet weight of 195 mg, thus providing a 51.28% drug loading; and Example 2 describes a 400 mg tablet with a total tablet weight of 768 mg, thus providing a 52.08% drug loading. These exemplified drug loadings, and associated excipient amounts, considerably limit the choice and amount of excipient that can be employed. This is even more the case when one appreciates that the above drug loading is based on imatinib free base, and for example the imatinib mesylate drug loading in Example 1 of WO 03/090720 is 61.3%.
The present invention now alleviates the above discussed problems as associated with the prior art and accordingly there is 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to
the total weight of said solid oral dosage form. In particular, it is preferred that a solid dosage form according to the present invention comprises said imatinib in an amount in the range of about 28.0 to 29.0%, even more preferably in an amount in the range of about 28.0 to 28.8%, based on the weight of imatinib free base compared to the total weight of said solid oral dosage form. It is further noted that in the case of a tablet composition according to the present invention as hereinafter described in greater detail, it is particularly preferred that the tablet comprises said imatinib in an amount in the range of about 28.0 to 28.5%, based on the weight of imatinib free base compared to the total weight of said tablet.
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 pharmaceutically acceptable excipients, said tablet comprising said imatinib in an amount in the range of about 27.0 to 29.0% based on the weight of imatinib free base 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said capsule. Preferred % amounts for said imatinib are as previously described.
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. A particularly preferred filler for use in a solid dosage form according to the present invention comprises microcrystalline cellulose, in particular for use in the intra-granular phase of either a tablet or capsule as hereinafter described. Suitably, a filler is included in an oral dosage form according to the present invention in an amount in the range of
about 15.0 to 30.0%, based on the weight thereof compared to the total weight of the solid oral dosage form, more preferably in an amount in the range of about 15.0 to 25.0%, and even more preferably in an amount in the range of about 15.0 to 20.0%, based on the weight thereof compared to the total weight of the solid oral dosage form.
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 methylcellulose (hypromellose) and microcrystalline cellulose (which as indicated above can also function as a filler). A preferred wet binder comprises hydroxypropyl methylcellulose and a preferred dry binder comprises microcrystalline cellulose. The amount of binder present can vary depending on the formulation process employed, but in the case of a formulation prepared by wet granulation then typically a wet binder is employed in an intra- granular phase in an amount in the range of about 2.0 to 4.0%, based on the weight thereof compared to the total weight of the solid oral dosage form, and wherein a dry binder is employed then this is present in a relatively higher amount, such as in an amount in the range of about 10.0 to 25.0%, more preferably in an amount in the range of about 10.0 to 23.0%, and even more preferably in an amount in the range of about 12.0 to 23.0%, based on the weight thereof compared to the total weight of the solid oral dosage form. Typically, and depending on the formulation process employed, then the dry binder might be employed in an extra-granular phase.
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). Preferred disintegrants are croscarmellose sodium (suitably present in an intra-granular phase as hereinafter described) and sodium starch glycolate (suitably present in an extra-granular phase as hereinafter described). These disintegrants are typically present in an amount in the range of about 17.0 to 25.0%, based on the weight thereof compared to the total weight of the solid oral dosage form. More preferably, such disintegrants are present in an amount in the range of about 19.0 to 22.0%, based on the weight thereof compared to the total weight of the solid oral dosage form, and typically where such % weights for disintegrants are provided herein then these are based on the total amount of disintegrant present both in intra- and extra-granular phases of a solid oral 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 in the range of about 0.1 to 1.0%, 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 in the range of about 0.25 to 3.0%, based on the weight thereof compared to the total weight of the solid oral dosage form. Preferably a lubricant is present in an extra-granular phase of a solid oral dosage form according to the present invention.
In the case where a solid oral dosage form comprises a tablet substantially as hereinbefore described, then it is preferred that the tablet comprises a film coated tablet. As referred to herein, "film-coated tablet" means a tablet core provided with a film coating, and a typical film coating employs hydroxypropyl methylcellulose (hypromellose) as a key constituent 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form. Preferably, the above process comprises a wet granulation process. Accordingly, there is still further 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 wet granulating said imatinib, or a pharmaceutically acceptable salt thereof, together with said one or more pharmaceutically acceptable excipients, so as to provide a solid oral dosage form comprising said imatinib in an amount in the range of about 23.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form. 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 a wet granulation process, 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 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 wet granulation process, blending with one or excipients of an extra-granular phase, and filling the resulting mixture into an appropriately sized capsule.
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. In 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:
Intra-granular phase:
Imatinib Mesylate 478.0 mg
Microcrystalline Cellulose 268.0 mg
Croscarmellose Sodium 206.0 mg
Hypromellose 32.0 mg
Ethanol 0.25 ml
Total Granule Weight: 984.0 mg
Extra-granular phase:
Microcrystalline Cellulose 280.2 mg
Sodium Starch Glycolate 86.0 mg
Colloid. Silicon Dioxide 7.6 mg
Magnesium Stearate 12.2 mg
Total Core Weight: 1370.0mg
Film coating:
Hypromellose 30.4 mg
Polyethylene Glycol 4.0 mg
Talc 10.0 mg
Yellow Iron Oxide 5.1 mg
Red Iron Oxide 0.5 mg
Total Tablet Weight: 1420.0 mg
% Drug Loading: 28.2%
1. Hypromellose was dissolved in the granulation solvent and mixed until a clear solution was obtained.
2. Imatinib mesylate, microcrystalline cellulose and croscarmellose sodium were mixed and subsequently granulated with the granulating solution, until granules were formed.
3. The wet granules were dried and sifted.
4. The granules were blended with microcrystalline cellulose and sodium starch glycolate. Subsequently, magnesium stearate and colloidal silicon dioxide were blended with the mixture.
5. The mixture was compressed with a suitable compressing machine.
6. The compressed tablets were coated with the film coating dispersion.
Example 2:
Intra-granular phase:
Imatinib Mesylate 478.0 mg
Microcrystalline Cellulose 268.0 mg
Croscarmellose Sodium 206.0 mg
Hypromellose 32.0 mg
Ethanol 0.25 ml
Total Granule Weight: 984.0 mg
Extra-granular phase:
Microcrystalline Cellulose 310.2 mg
Sodium Starch Glycolate 86.0 mg
Colloid. Silicon Dioxide 7.6 mg
Magnesium Stearate 12.2 mg
Total Core Weight: 1400.0mg
% Drug Loading: 28.6%
1. Hypromellose was dissolved in the granulation solvent and mixed until a clear solution was obtained.
2. Imatinib mesylate, microcrystalline cellulose and croscarmellose sodium were mixed and subsequently granulated with the granulating solution, until granules were formed.
3. The wet granules were dried and sifted.
4. The granules were blended with microcrystalline cellulose and sodium starch glycolate. Subsequently, magnesium stearate and colloidal silicon dioxide were blended with the mixture.
5. The mixture was filled into capsules.
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 in the range of about 27.0 to 29.0% 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, which comprises said imatinib in an amount in the range of about 28.0 to 29.0%, based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.
3. A dosage form according to claim 2, which comprises said imatinib in an amount in the range of about 28.0 to 28.8% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.
4. A dosage form according to claim 3, which comprises said imatinib in an amount in the range of about 28.0 to 28.5% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.
5. A dosage form according to any of claims 1 to 4, which is a tablet.
6. A dosage form according to any of claims 1 to 4, which is a capsule.
7. A solid oral dosage form which is a 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said tablet.
8. A solid oral dosage form which is 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said capsule.
9. A dosage form according to any of claims 1 to 8, which further comprises one or more fillers selected from the group consisting of sugars, sugar alcohols and polymeric glycosides.
10. A dosage form according to claim 9, wherein said filler comprises a polymeric glycoside.
11. A dosage form according to claim 10, wherein said polymeric glycoside comprises microcrystalline cellulose.
12. A dosage form according to any of claims 9 to 11, wherein said filler is present in an amount in the range of about 15.0 to 30.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
13. A dosage form according to claim 12, wherein said filler is present in an amount in the range of about 15.0 to 25.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
14. A dosage form according to claim 13, wherein said filler is present in an amount in the range of about 15.0 to 20.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
15. A dosage form according to any of claims 1 to 14, which further comprises one or more binders.
16. A dosage form according to claim 15, wherein said binder comprises one or more of polyvinylpyrrolidone, hydroxypropyl methylcellulose and microcrystalline cellulose.
17. A dosage form according to claim 16, which comprises hydroxypropyl methylcellulose and microcrystalline cellulose as binders.
18. A dosage form according to claims 15 to 17, which employs a wet binder in an intra-granular phase in an amount in the range of about 2.0 to 4.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
19. A dosage form according to claim 18, wherein said wet binder comprises hydroxypropyl methylcellulose.
20. A dosage form according to claims 15 to 19, which employs a dry binder in an extra-granular phase in an amount in the range of about 10.0 to 25.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
21. A dosage form according to claim 20, wherein said dry binder is present in an amount in the range of about 10.0 to 23.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
22. A dosage form according to claim 21, wherein said dry binder is present in an amount in the range of about 12.0 to 23.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
23. A dosage form according to any of claims 1 to 22, which further comprises one or more disintegrants.
24. A dosage form according to claim 23, wherein said disintegrant is selected from the group consisting of crospovidone, croscarmellose and salts thereof, starches, modified starches and hydroxypropyl cellulose with a low degree of substitution.
25. A dosage form according to claim 24, which employs croscarmellose sodium and sodium starch glycolate as disintegrants.
26. A dosage form according to any of claims 23 to 25, wherein said disintegrant is present in an amount in the range of about 17.0 to 25.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
27. A dosage form according to claim 26, wherein said disintegrant is present in an amount in the range of about 19.0 to 22.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
A dosage form according to any of claims 1 to 27, which comprises one or more glidants.
29. A dosage form according to claim 28, wherein said glidant is selected from the group consisting of colloidal silicon dioxide, calcium silicates and talcum.
30. A dosage form according to claim 29, wherein said glidant comprises colloidal silicon dioxide.
31. A dosage form according to any of claims 28 to 30, wherein said glidant is present in an amount in the range of about 0.1 to 1.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
32. A dosage form according to any of claims 1 to 31, which comprises one or more lubricants.
33. A dosage form according to claim 32, wherein said lubricant is selected from the group consisting of stearic acid or salts thereof.
34. A dosage form according to claim 33, wherein said lubricant comprises magnesium stearate.
35. A dosage form according to any of claims 32 to 34, wherein said lubricant is present in an amount in the range of about 0.25 to 3.0%, based on the weight thereof compared to the total weight of said solid oral dosage form.
36. A dosage form according to any of claims 1 to 35, wherein said imatinib comprises imatinib mesylate.
37. A dosage form according to claim 36, wherein said imatinib mesylate is present as crystalline form alpha.
38. 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, according to any of claims 1 to 37, 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 in the range of about 27.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.
39. A process according to claim 38, wherein said process comprises a wet granulation process.
40. 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 wet granulating said imatinib, or a pharmaceutically acceptable salt thereof, together with said one or more pharmaceutically acceptable excipients, so as to provide a solid oral dosage form comprising said imatinib in an amount in the range of about 23.0 to 29.0% based on the weight of imatinib free base compared to the total weight of said solid oral dosage form.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1204810.4 | 2012-03-20 | ||
| GBGB1204810.4A GB201204810D0 (en) | 2012-03-20 | 2012-03-20 | Pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013139826A1 true WO2013139826A1 (en) | 2013-09-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2013/055764 WO2013139826A1 (en) | 2012-03-20 | 2013-03-20 | Pharmaceutical compositions comprising imatinib |
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|---|---|
| GB (1) | GB201204810D0 (en) |
| WO (1) | WO2013139826A1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999003854A1 (en) | 1997-07-18 | 1999-01-28 | Novartis Ag | Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use |
| WO2003090720A1 (en) | 2002-04-23 | 2003-11-06 | Novartis Ag | High drug load tablet |
| US20070036850A1 (en) * | 2005-08-15 | 2007-02-15 | Siegfried Generics International Ag | Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound |
| WO2011157450A1 (en) * | 2010-06-18 | 2011-12-22 | Krka, D. D., Novo Mesto | New polymorphic form of imatinib base and preparation of salts thereof |
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2012
- 2012-03-20 GB GBGB1204810.4A patent/GB201204810D0/en not_active Ceased
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2013
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999003854A1 (en) | 1997-07-18 | 1999-01-28 | Novartis Ag | Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use |
| WO2003090720A1 (en) | 2002-04-23 | 2003-11-06 | Novartis Ag | High drug load tablet |
| US20070036850A1 (en) * | 2005-08-15 | 2007-02-15 | Siegfried Generics International Ag | Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound |
| WO2011157450A1 (en) * | 2010-06-18 | 2011-12-22 | Krka, D. D., Novo Mesto | New polymorphic form of imatinib base and preparation of salts thereof |
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| GB201204810D0 (en) | 2012-05-02 |
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