Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1994-03-04
1996-04-30
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424488, 424458, 424470, A61K 914
Patent
active
055123023
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a process for the preparation of pharmaceutical compositions containing 2-(4-isobutylphenyl) propionic acid or a salt thereof, to compositions produced by said process and to pharmaceutical formulations containing said compositions.
(.+-.)-2-(4-Isobutylphenyl)propionic acid, ibuprofen, is a potent and well tolerated anti-inflammatory, analgesic and anti-pyretic compound. The racemic mixture consists of two enantiomers, namely S(+)-2-(4-isobutylphenyl)propionic acid or S(+)-ibuprofen and R(-)-2-(4-isobutylphenyl)propionic acid or R(-)-ibuprofen. It is known that S(+)-ibuprofen is the active agent and that some R(-)-ibuprofen is converted into S(+)-ibuprofen in humans. The drug has been marketed as the racemic mixture but recent evidence has suggested, however, that in certain circumstances it may be advantageous to administer S(+)-ibuprofen.
The simplest and most cost-effective way to produce a tablet is to dry blend the active ingredient with inexpensive, readily available excipients and to then directly compress the mixture obtained into tablets. For example, aspirin may be dry mixed with starch and the mixture directly compressed into tablets. This method is not suitable for ibuprofen as satisfactory tablets are not produced. Instead the technique of wet granulation is usually employed to produce tablets containing ibuprofen. This means that extra processing steps are required which raise the cost of the tabletting process.
An additional problem is that when ibuprofen is wet granulated by conventional methods, it has been necessary to include a relatively high percentage of excipients to produce satisfactory tablets. As a result, the size of the tablet is increased and consequently high dosage tablets have reduced acceptability to certain patients. There is therefore an acknowledged need for a method of producing smaller ibuprofen tablets containing a high percentage of drug and for an inexpensive, simple process to produce an ibuprofen composition which may be directly compressed into tablets. Various methods have been proposed but an entirely satisfactory solution has yet to be found.
U.S. Pat. No. 4,609,675 discusses the problems of wet granulations containing ibuprofen and discloses a granule comprising 85 to 99% of ibuprofen and 1 to 15% of croscarmellose sodium, a comparatively expensive excipient. The granule is formed by dry mixing the components, passing the resulting mixture through a roller compactor or slugging the composition and thereafter sizing the material obtained.
In the Journal of Pharmaceutical Sciences Vol. 78, p68 (1989), there is disclosed a method of preparing controlled release microspheres of ibuprofen with acrylic polymers by agglomeration in an ethanol/water system. There is no suggestion that this method could be applied to the preparation of conventional release tablets with a controllable microstructure.
EP 298,666 describes a spray dried ibuprofen composition suitable for direct compression into tablets consisting essentially of a spray dried dispersion of ibuprofen in water, pregelatinised starch, a disintegrant and a wetting agent for the ibuprofen. It also discloses tablets prepared from said compositions. This method suffers from several disadvantages. The two principal disadvantages are that the physical properties of the resultant granule cannot be easily adjusted and that the process is very costly both in terms of capital equipment expenditure and running costs due to the high energy input required for the spray drying process.
U.S. Pat. No. 4,911,921 discloses a granular composition comprising 85% or more ibuprofen, a binder, polyvinylpyrrolidone in a film forming amount and moisture up to 2.0% , said granulation being in the form of agglomerates of ibuprofen and binder held together by binder and polyvinylpyrrolidone. The binder is selected from a group consisting of starches, celluloses and sugars. The composition is prepared by fluidising the ibuprofen with a portion of the binder, spraying this blend with a dispersion of the polyviny
REFERENCES:
patent: 5087454 (1992-02-01), Duerholz et al.
patent: 5240712 (1993-08-01), Smith et al.
patent: 5260337 (1993-11-01), Sims et al.
patent: 5266723 (1993-11-01), Hanna et al.
patent: 5332834 (1994-07-01), Bhattacharya et al.
Journal of Pharmaceutical Sciences 1989, 78, 68-72, Kawashima et al.
Atkin Graham J.
Drew Peter
Turner John L.
Benston, Jr. William E.
Page Thurman K.
The Boots Company PLC
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