Solid dosage form production
The present invention utilizes 3D printing technology, specifically fused filament fabrication (FFF) 3D printing, to produce solid dosage forms, such as pharmaceutical tablets. The production process utilizes novel printing filaments, typically on a spool, which contain the active ingredient. Such active-containing filaments have proved to be extremely robust and the principles outlined in the present disclosure provide access to a variety of viable formulations directly from a 3D printer. This, for the first time, affords a viable means for the in situ (e.g. within a pharmacy) 3D printing of personalized medicines tailored to a patient's needs. The invention also relates to purpose-built software for operating the printing apparatus, as well as local, national and global systems for monitoring the real time operation of a plurality of printing apparati to enable facile detection of malfunctions, thereby making regulatory approval viable and facilitating regulatory compliance.
1 . A printer cartridge for a fused filament fabrication (FFF) 3D printer, comprising:
a housing containing an active ingredient-containing printing filament, wherein the active ingredient-containing printing filament consists of, consists essentially of, or comprises an active ingredient-containing filament composition comprising: the active ingredient and an active ingredient carrier;
wherein the printer cartridge is releasably engageable with or releasably installable within the printer;
wherein the printer cartridge further comprises attachment mechanisms;
wherein the printer cartridge further comprises an integral printer nozzle through which the active ingredient-containing printing filament is deliverable during printing.
2 . The printer cartridge as claimed in claim 1 , wherein the printer nozzle is selectively heatable.
3 . The printer cartridge as claimed in claim 2 , wherein the printer nozzle is selectively heatable via the printer.
4 . The printer cartridge as claimed in claim 1 , wherein the printer cartridge further comprises a conveyor mechanism operable to convey the active ingredient-containing printing filament through a printer nozzle during printing.
5 . The printer cartridge as claimed in claim 4 , wherein the conveyor mechanism comprises a feed channel along which the active ingredient-containing printing filament is feedable during conveyance to the printer nozzle; wherein the feed channel comprises one or more conveyor elements operable to frictionally engage or grip the active ingredient-containing printing filament as the active ingredient-containing printing filament is conveyed.
6 . The printer cartridge as claimed in claim 5 , wherein one or more of the conveyor elements comprises a roller or set of rollers which engage with or grip the active ingredient-containing printing filament during conveyance thereof.
7 . The printer cartridge as claimed in claim 4 , wherein the conveyor mechanism is releasably engageable with a mechanical drive mechanism associated with or integral to the printer.
8 . The printer cartridge as claimed in claim 1 , wherein the printer cartridge is sealed.
9 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament is formed via hotmelt extrusion of a hotmelt mixture prepared by mixing together at least the pharmaceutical active ingredient and the active ingredient carrier.
10 . The printer cartridge as claimed in claim 9 , wherein the mixing together is performed at a mixing temperature (T 1 ) that is between 70 and 150° C. and the hotmelt extrusion is performed at a hotmelt extrusion temperature (T 2 ) that is 10 to 50° C. lower than the mixing temperature.
11 . The printer cartridge as claimed in claim 10 , wherein the active ingredient carrier is a polymer having a glass transition temperature at least 50° C. lower than the melting point of the pharmaceutical active ingredient.
12 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament comprises a plurality of active ingredients.
13 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament comprises a disintegrant.
14 . The printer cartridge as claimed in claim 1 , wherein the active ingredient carrier is selected from the group consisting of:
an (optionally alkyl-, suitably methyl-or ethyl-) acrylate, methacrylate and/or ethacrylate polymer or copolymer;
a cellulose or cellulose derivative;
polyvinyl alcohol (PVA);
poly (lactic-co-glycolic acid) (PLGA);
a PVP or PVP-based carrier; and
a PEG or PEG-based carrier; and
any combination thereof.
15 . The printer cartridge as claimed in claim 1 , wherein the active ingredient carrier comprises at least one polymer or co-polymer selected from the group consisting of:
an acrylate, methacrylate and/or ethacrylate copolymer comprising amine-containing monomeric units;
an alkyl-acrylate, alkyl-methacrylate and/or alkyl-ethacrylate copolymer comprising amine-containing monomeric units;
an methyl-acrylate, methyl-methacrylate and/or methyl-ethacrylate copolymer comprising amine-containing monomeric units;
an ethyl-acrylate, ethyl-methacrylate and/or ethyl-ethacrylate copolymer comprising amine-containing monomeric units;
an acrylate, methacrylate and/or ethacrylate polymer or copolymer free of any amine-containing monomeric units;
an alkyl-acrylate, alkyl-methacrylate and/or alkyl-ethacrylate polymer or copolymer free of any amine-containing monomeric units;
an methyl-acrylate, methyl-methacrylate and/or methyl-ethacrylate polymer or copolymer free of any amine-containing monomeric units;
an ethyl-acrylate, ethyl-methacrylate and/or ethyl-ethacrylate polymer or copolymer free of any amine-containing monomeric units;
a cellulose or cellulose derivative;
a polyvinyl alcohol (PVA); and
a poly (lactic-co-glycolic acid) (PLGA).
16 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament further comprises a plasticizer.
17 . The printer cartridge as claimed in claim 16 , wherein the plasticizer is selected from the group consisting of one or more of triethylcitrate (TEC), glycerol, castor oil, oleic acid, glycerol, triacetin and a polyalkylene glycol.
18 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament further comprises one or more fillers, where the filler is different from the active ingredient carrier, and wherein the filler has a melting point of at least 200° C.
19 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament comprises greater than or equal to 5 wt % active ingredient.
20 . The printer cartridge as claimed in claim 1 , wherein the active ingredient-containing printing filament has a diameter or maximum thickness of between 0.1 mm and 5 mm.
21 . The printer cartridge as claimed in claim 1 , wherein the printer cartridge is configured for releasable docking within a docking station within the printer.
22 . The printer cartridge as claimed in claim 1 , wherein the printer cartridge is a disposable printer cartridge.