Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1997-08-18
2000-05-30
Harrison, Peter H.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424451, 424452, 424457, 424464, 424465, 424469, 424489, 424502, A61J 302, A61J 306, A61K 926, B29B 000
Patent
active
060688556
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND AND SUMMARY OF THE INVENTION
The present invention relates generally to a method of manufacturing pharmaceutical dosage forms, for human or veterinary use, preferably sustained release particles, such particles having diameters ranging from 0.1 to 3.0 mm. Such particles may contain analgesics, such as morphine, or other active ingredients. The present invention also relates to dosage forms obtained by processing of the aforesaid particles, such as tablets, suppositories or pessaries.
In our co-pending British Patent Application No. 9404928.5 we describe a process for the manufacture of particles, preferably sustained release particles, which comprises
(a) mechanically working in a high-shear mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150.degree. C. and optionally a release control component comprising a water-soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften whereby it forms agglomerates;
(b) breaking down the agglomerates to give controlled release particles; and optionally
(c) continuing mechanically working optionally with the addition of a low percentage of the carrier or diluent; and optionally
(d) repeating steps (c) and possibly (b) one or more times.
DETAILED DESCRIPTION OF THE INVENTION
We have now found that satisfactory results may also be obtained if, instead of classifying the agglomerated material in stage b) the material from stage a) is formed into extrudates of predetermined size, and in preferred embodiments, higher yields and/or higher drug loadings, and greater uniformity of size, than in the earlier process first mentioned above still with satisfactory controlled release properties may be achieved.
The present invention thus includes in one aspect a process for the manufacture of particles, preferably sustained release particles, which comprises:
(a) mechanically working in a high-shear mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35 to 150.degree. C. and optionally a release control component comprising a water soluble fusible material or a particulate, soluble or insoluble, organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften, whereby it forms agglomerates; and then
(b) extruding the resulting material.
The extrusion may be carried out so as to form a rod like extrudate which may be cut or moulded to form unit dosage forms e.g. tablets or suppositories, directly.
Preferably the extrusion is through a plurality of orifices and the extrudate is formed into pieces. In more preferred embodiments the extrusion is through a plurality of small orifices e.g. about 0.25 mm to 1.5 mm e.g. 0.5 mm or 1.0 mm diameter and the extrudate is formed into short lengths of e.g. 0.5 to 1.5 mm e.g. 1.0 mm, suitably by cutting.
A preferred process according to the invention comprises the further steps,
(c) of continuing mechanically working the pieces formed from the extrudate, optionally with a further addition of a low percentage of the carrier or diluent; and
(d) optionally repeating step (c) and possibly (b) one or more e.g. up to five times.
Extrusion and forming into short lengths by cutting may be carried out using e.g. an Alexanderwerk, Caleva or Nica machine.
Extrusion operations are well known in the formulation field and are described, for example in Pharmaceutical Dosage forms, Volume 2, Ed. Lieberman and Lachman, Marcel Dehker Inc, New York and Basel.
This process is capable of giving a high yield, generally greater than 85%, and preferably greater than 90% of particles in a desired size range, with a desired in vitro release rate and, uniformity of release rate.
The resulting particles may be sieved to eliminate any oversized or undersized material then formed into the desired dosage units by
REFERENCES:
patent: Re33093 (1989-10-01), Schiraldi et al.
patent: 2738303 (1956-03-01), Blythe et al.
patent: 3065143 (1962-11-01), Christenson et al.
patent: 3652589 (1972-03-01), Flick et al.
patent: 3830934 (1974-08-01), Flick et al.
patent: 3845770 (1974-11-01), Theeuwes et al.
patent: 3880991 (1975-04-01), Yolles
patent: 3916889 (1975-11-01), Russel
patent: 3950508 (1976-04-01), Mony et al.
patent: 3965256 (1976-06-01), Leslie
patent: 3974157 (1976-08-01), Shetty et al.
patent: 4013784 (1977-03-01), Speiser
patent: 4063064 (1977-12-01), Saunders
patent: 4076798 (1978-02-01), Casey et al.
patent: 4088864 (1978-05-01), Theuwes et al.
patent: 4132753 (1979-01-01), Blichare et al.
patent: 4173417 (1979-11-01), Kruder
patent: 4230687 (1980-10-01), Sair et al.
patent: 4259314 (1981-03-01), Lowey
patent: 4265875 (1981-05-01), Byrne et al.
patent: 4292300 (1981-09-01), Byrne et al.
patent: 4310483 (1982-01-01), Dorfel et al.
patent: 4343789 (1982-08-01), Kawata et al.
patent: 4344431 (1982-08-01), Yolles
patent: 4346709 (1982-08-01), Schmitt
patent: 4366172 (1982-12-01), Lednicer
patent: 4374082 (1983-02-01), Hochschild
patent: 4380534 (1983-04-01), Fukui et al.
patent: 4389393 (1983-06-01), Schor et al.
patent: 4406883 (1983-09-01), Byrne et al.
patent: 4421736 (1983-12-01), Walters et al.
patent: 4483847 (1984-11-01), Augart
patent: 4533562 (1985-08-01), Ikegami et al.
patent: 4613619 (1986-09-01), Sleigh et al.
patent: 4621114 (1986-11-01), Watanabe
patent: 4649042 (1987-03-01), Davis et al.
patent: 4720384 (1988-01-01), DiLuccio et al.
patent: 4762220 (1988-08-01), Lutke
patent: 4764378 (1988-08-01), Keith et al.
patent: 4778676 (1988-10-01), Yang et al.
patent: 4797410 (1989-01-01), El-Fakahany
patent: 4801458 (1989-01-01), Hidaka et al.
patent: 4801460 (1989-01-01), Goertz et al.
patent: 4806337 (1989-02-01), Snipes et al.
patent: 4818450 (1989-04-01), Hall et al.
patent: 4828836 (1989-05-01), Elger et al.
patent: 4834984 (1989-05-01), Goldie et al.
patent: 4834985 (1989-05-01), Elger et al.
patent: 4842761 (1989-06-01), Rutherford
patent: 4844907 (1989-07-01), Elger et al.
patent: 4844909 (1989-07-01), Goldie et al.
patent: 4861598 (1989-08-01), Oshlack
patent: 4879108 (1989-11-01), Yang et al.
patent: 4880585 (1989-11-01), Klimesch et al.
patent: 4880830 (1989-11-01), Rhodes
patent: 4882151 (1989-11-01), Yang et al.
patent: 4882152 (1989-11-01), Yang et al.
patent: 4882153 (1989-11-01), Yang et al.
patent: 4882155 (1989-11-01), Yang et al.
patent: 4882156 (1989-11-01), Yang et al.
patent: 4882157 (1989-11-01), Yang et al.
patent: 4882159 (1989-11-01), Yang et al.
patent: 4882167 (1989-11-01), Yang
patent: 4894234 (1990-01-01), Sharma et al.
patent: 4917899 (1990-04-01), Geoghegan et al.
patent: 4925675 (1990-05-01), Giannini et al.
patent: 4935246 (1990-06-01), Ahrens
patent: 4957681 (1990-09-01), Klimesch et al.
patent: 4959208 (1990-09-01), Chakrabarti et al.
patent: 4967486 (1990-11-01), Doelling
patent: 4970075 (1990-11-01), Oshlack
patent: 4975284 (1990-12-01), Stead et al.
patent: 4987136 (1991-01-01), Kreek et al.
patent: 4990341 (1991-02-01), Goldie et al.
patent: 4992100 (1991-02-01), Koepff et al.
patent: 4994227 (1991-02-01), Dietz et al.
patent: 5007790 (1991-04-01), Shell
patent: 5023089 (1991-06-01), Sakamoto et al.
patent: 5026560 (1991-06-01), Makino et al.
patent: 5030400 (1991-07-01), Danielson et al.
patent: 5035509 (1991-07-01), Kruder
patent: 5049394 (1991-09-01), Howard et al.
patent: 5055307 (1991-10-01), Tsuru et al.
patent: 5071646 (1991-12-01), Malkowska et al.
patent: 5073379 (1991-12-01), Klimesh et al.
patent: 5102668 (1992-04-01), Eichel et al.
patent: 5126145 (1992-06-01), Evenstad
patent: 5132142 (1992-07-01), Jones et al.
patent: 5133974 (1992-07-01), Paradissis et al.
patent: 5147593 (1992-09-01), Huttllin
patent: 5162117 (1992-11-01), Stupak et al.
patent: 5167964 (1992-12-01), Muhammed et al.
patent: 5169645 (1992-12-01), Shukla et al.
patent: 5178868 (1993-01-01), Malmqvist-Granlund et al.
patent: 5183690 (1993-02
Knott Trevor John
Leslie Stewart Thomas
Mohammad Hasssan
Prater Derek Allan
Euro-Celtique S. A.
Harrison Peter H.
LandOfFree
Pharmaceutical composition containing a fusible carrier and meth does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical composition containing a fusible carrier and meth, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition containing a fusible carrier and meth will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1908238