Patent application EP16460037A (EP), filed 2016-06-17
Publication number: EP3257499A1
Title: PROCESS FOR PREPARATION OF IMATINIB METHANESULFONATE CAPSULES
Abstract: The process for preparation of hard gelatin capsules of imatinib methanesulfonate having a decreased volume consists in that the imatinib methanesulfonate granulate designated for the filling the capsules is deprived of a fraction of the particles size below 0.250 mm, extragranular ingredients are added and thus obtained blend is used to fill the hard gelatin capsules. The object of the invention is also the medicinal product in the form of hard gelatin capsules comprising imatinib methanesulfonate in an amount corresponding to the 100 mg imatinib dose in capsule size number 4 and the 400 mg imatinib dose in capsule size number 0el. The capsules are characterized by more advantageous dissolution profiles and better bioavailability in comparison with capsules manufactured from non-separated granulate.
IPC codes: A61K  31/   506            A I
A61K   9/    16            A I
Claims: number: 1
text: A process for preparation of imatinib methanesulfonate hard capsules having a reduced volume, wherein :
number: 2
text: The process according to claim 1, wherein the imatinib methanesulfonate granulate is deprived of the smallest size particles by separating it on the sieves with 0.1 mm to 0.250 mm openings.
number: 3
text: The process according to claim 2, wherein the imatinib methanesulfonate granulate is separated on the sieve with 250 mm openings.
number: 4
text: The process according to claim 2, wherein the imatinib methanesulfonate granulate is separated on the sieve with 0.125 mm openings.
number: 5
text: The process according to any of claims 1 to 3, wherein the granulate of imatinib methanesulfonate in α-crystal form is used for separating process.
number: 6
text: The process according to claim 5, wherein the granulate obtained by granulating imatinib methanesulfonate in α-crystal form by using a mixture of isopropyl alcohol and water is used for separating process.
number: 7
text: The process according to claim 6, wherein the granulate obtained by granulating imatinib methanesulfonate in α-crystal form by using a mixture of isopropyl alcohol and water in the weight ratio between 80:20 and 20:80 w/w is used for the separating process.
number: 8
text: The process according to any of claims 1 to 7, wherein the used extragranular excipients comprise substances which improve flow properties of the granulate, like glidants and antielectrostatic agents.
number: 9
text: The process according to claim 8, wherein excipients selected from the group comprising stearic acid, stearic acid salts with alkaline earth metals, colloidal silica, talc and other known additives are used as extragranular excipients.
number: 10
text: The process according to claim 1, wherein the separated dusty fraction is returned to the process of preparation of the initial granulate.
number: 11
text: The process according to any of claims 1 to 9, wherein the blend of imatinib methanesulfonate from step b) in an amount corresponding to the 100 mg imatinib dose is filled into a capsule number 4.
number: 12
text: The process according to any of claims 1 to 9, wherein a blend of imatinib methanesulfonate from step b) in an amount corresponding to the 400 mg imatinib dose is filled into a capsule number 0el.
number: 13
text: Medicinal product manufactured in accordance to any of claims 1 to 9, in the form of hard gelatin capsules which comprise imatinib methanesulfonate in an amount corresponding to the 100 mg imatinib dose in a capsule size number 4.
number: 14
text: Medicinal product manufactured in accordance to any of claims 1 to 9 in the form of hard gelatin capsules which comprise imatinib methanesulfonate in an amount corresponding to the 400 mg imatinib dose in a capsule size number 0el.
Office action: search_report, dated 2017-12-20
Rejection reasons: novelty_epc_54
inventive_step_epc_56
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severity: novelty_destroying
Final disposition: pending (2017-12-20)