Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1997-02-04
2001-09-25
Dodson, Shelley A. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S464000, C424S474000, C424S475000
Reexamination Certificate
active
06294200
ABSTRACT:
PRIOR ART
In the field of pharmaceutical technology, manifold are the kinds of tablets manufactured in the last years in order to obtain the release of the active substance vehiculated into them at a constant rate in time. These tablets may determine a prolonged “therapeutic covering” that is the maintenance of therapeutically effective plasmatic levels of the active substance.
Examples of such embodiments are the so called “reservoir” systems, the “OROS” osmotic pumps and the “push-pull” systems, such as those for example described in the U.S. Pat. No. 4,160,020 (1979). These systems, correctly working, imply the advantages of a possible reduction of the daily total dosage with respect to the traditional pharmaceutical forms and of a posological simplification and therefore a better acceptability for the patient.
Together with these advantages, there are both structural and functional drawbacks, which may drastically limit and/or prevent from using for long periods said systems.
The most serious disadvantages reside in that their preparation encompasses the use of rather complex polymeric materials; for example the OROS osmotic pump coating consists of insoluble polymeric material which is moreover not biodegradable in the gastrointestinal tract and this may cause accumulation phenomena in the intestine of the exhausted coatings with possible intestinal obstruction.
Lower attention has been paid to the realization of pulsating release pharmaceutical forms, in other words systems capable of releasing one or more active substances at subsequent pulses according to a program which takes into account the circadian rhythms of particular pathological symptoms.
A pharmaceutical form belonging to this type is described in the U.S. Pat. No. 4,865,849, in which a three layers pharmaceutical tablet, is characterized in that two out of these 3 layers are coated with a polymeric material impermeable and insoluble in aqueous fluids having acid pH, but soluble in an alkaline medium.
This tablet, even though innovative, cannot be manufactured on an industrial scale by using the current productive technology.
An improvement to this therapeutic system is represented by U.S. Pat. No. 5,487,901, wherein a tablet engineered for a release in subsequent times of the active substances is produced by:
a) preparing a tablet having three overlapping layers and wherein the upper layer comprises an active substance, the intermediate layer optionally contains the same or a different active substance from that contained in the upper layer, but has essentially the function of a barrier layer, finally the lower layer contains an active substance. In this three layers tablet the intermediate layer (barrier) is able to determine the time interval between the release of the first and the second dose of the drug contained in the upper and lower layers respectively.
b) completely coating the tablet by means of a film consisting of an impermeable polymeric material.
c) removing the polymeric coating from the upper surface (recognizable since it shows a prominent portion) of the tablet by abrasion thus allowing the immediate release of the active substance quantity contained in said upper layer.
Also this realization shows nevertheless productive drawbacks determined by the fact that, during the abrasion phase, a part of the active substance contained in the upper layer is removed with possible negative repercussions on the uniformity of the content of the tablets. A further complication may reside in the polymeric material used for the coating, which, although being biocompatible and biodegradable, may request, for the biodegradability, a prolonged period of time and cause the possible persistence of the empty coating in the final tract of the intestine.
SUMMARY
The pharmaceutical tablet capable of releasing the active substance in subsequent and predeterminable times according to the present invention allows to overcome the drawbacks of the prior art. Said tablet is characterized by the following structure:
a) a core consisting of three layers and obtained by compression, in which
the upper layer contains an active substance which is immediately released when the tablet comes into contact with an aqueous medium or with gastric or intestinal fluid;
the intermediate layer optionally containing the active substance has a suitable composition to form a barrier able to determine a time interval between the release of the active substance contained in the upper layer and the one contained in the lower layer;
the lower layer may present the same or a different formulation from that of the upper layer, the same or a different active substance from that contained in the upper layer, and it may be formulated to have the release of the active substance with a prefixed kinetics;
b) a polymeric coating of the lower and lateral surface of said core, optionally coating an active substance, obtained by compression, able to form a barrier impermeable to the aqueous medium for a predeterminable period of time.
The tablet so obtained may be optionally further coated by a polymeric film soluble in water or in aqueous fluids.
This tablet is prepared by the following procedure:
in the first step the three layers core is produced by a compression procedure;
in the second step the core is coated by compression on the lower and lateral surface with suitable polymeric materials having controlled permeability formulated with excipients able to give the mass suitable compressibility characteristics.
According to a further embodiment of the present invention the core consists of two layers, wherein the upper layer is the barrier-layer and the lower layer contains the fast release active substance, said tablet being covered by said impermeable coating on the lateral and lower surface while on the upper surface a layer containing the fast release active substance is applied.
According to another further embodiment of the present invention the three layers core is characterized by being covered on the lateral and the lower surface by said impermeable coating, whereas on the upper surface of the upper layer comprising the fast release active substance a further layer containing the fast release active substance is applied.
REFERENCES:
patent: 4160020 (1979-07-01), Ayer et al.
patent: 4865849 (1989-09-01), Conte et al.
patent: 4898733 (1990-02-01), DePrince et al.
patent: 5213808 (1993-05-01), Bar-Shalom et al.
patent: 5487901 (1996-01-01), Conte et al.
patent: 5631022 (1997-05-01), Mandel et al.
patent: 1022171 (1966-03-01), None
patent: 1346609 (1974-02-01), None
Conte Ubaldo
Maggi Lauretta
Dodson Shelley A.
Jagotec AG
Leydig Voit & Mayer Ltd
LandOfFree
Pharmaceutical tablet suitable to deliver the active... 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 tablet suitable to deliver the active..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical tablet suitable to deliver the active... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2512148