Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-06-22
1998-07-21
Zitomer, Fred
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424489, 424493, 424494, 424500, A61K 950, A61K 958, A61K 914, A61K 922
Patent
active
057832153
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to controlled release beads and a novel pharmaceutical preparation containing a core around which is a drug-containing layer e.g. a layer containing an active substance, i.e. a practically insoluable active substance, preferably furosemid to the use of said preparation and to a process for preparing the same.
BACKGROUND OF THE INVENTION
The present invention provides a novel a pharmaceutical multiple unit dose preparation with very favourable characteristics which may withstand mechanical stress, i.e. during compaction. These favourable mechanical characteristics are advantageous when dealing with multiple unit dose systems comprising modified or controlled release properties.
A common problem with multiple unit dose systems designated to have modified or controlled release properties is their sensitivity to mechanical stress, e.g. compaction stress, giving rise to rupturing and cracking of the release controlling membrane (Bechard and Leroux 1992) or fragmentation of the core (Magnatiand Celik 1994).
Multiple unit dosage systems may be filled into capsules or sachets, thus requiring sufficient mechanical properties to withstand processing. It may even be advantageous to compact multiple units into tablets, subjecting the systems to significant mechanical stress.
According to the present invention the problem of mechanical suitability mentioned above has been overcome by using inert and non-soluble cores of glass or sand particles or soluble cores such as sugar spheres capable of withstanding mechanical stress, in combination with a plasticizing layer of a hydrophilic polymer containing the active substance, optionally with additional layers of the polymer not containing the active substance, layered between the core and the release controlling membrane.
PRIOR ART
In abstract PDD 7397 from AAPs congress, USA, Pharmaceutical Research (supplement), 1993, it is described that the coating of pellets provides a physical protection of the pellet core which must remain intact and have suitable mechanical properties in order to be resistant to fragmentation during compaction of the tablet. Fragmentation was, however, found to be between 18 and 42% for ethylcellulose pellets.
In Drug Development and Industrial Pharmacy, 18(8), 1927-1944 (1992), films manufactured from an ethyl cellulose pseudolatex dispersion plasticized with 24% DBS, suitable for the controlled release of chlorpheniramine maleate from small pellets with a size of 250-840 mm, are described. These films do not, however, have the appropriate mechanical properties to withstand compaction forces without rupturing, and the controlled release properties of the compacted pellets are thus lost during the process.
In "Compaction studies on pellets", L. Maganti and M. Celik, International Journal of Pharmaceutics, 95 (1993) 29-42, compaction characteristics of pellets, i.e. cores made from microcrystalline cellulose, dicalciumphosphate, lactose and propranolol HCl, are described, and it is concluded that the pellets exhibit elastic deformation and brittle fragmentation, resulting in compacts of lower tensile strength.
In "Compaction studies on pellets", L. Maganti and M. Celik, International Journal of Pharmaceutics, 103 (1994) 55-67, it is described that the addition of a coating material alters the deformation characteristics of uncoated pellets. Further, it is shown that coated pellets lost their sustained release characteristics after compaction.
U.S. Pat. No. 4,713,248 describes a controlled release multiple unit formulation containing an active substance coated with a water based film comprising a homogeneous combination of water-dispersable film forming agent and a polymeric substance which impart compressability to the coating.
EP 361 874 describes a process for the preparation of a core by spraying core granules with a dispersion of a low substituted hydroxypropylcellulose, and if necessary simultaneously applying a dusting powder. The dispersion or the dusting powder can be incorporated wi
REFERENCES:
patent: 4713248 (1987-12-01), Kj.o slashed.rnaes
patent: 5026560 (1991-06-01), Makino
Abstract PDD 7397 from AAP's Congress, U.S.A., Pharmaceutical Research (Supplement), 1993.
Drug Development and Industrial Pharmacy, 18(18), 1927-1944 1992.
International Journal of Pharmaceutics, 95 (1993), 29-42.
International Journal of Pharmaceutics, 103 (1994), 55-67.
Arwidsson Hans
Stubberud Lars
Astra Aktiebolag
Zitomer Fred
LandOfFree
Pharmaceutical preparation 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 preparation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical preparation will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1644504