Bioadhesive tablets

Details Bioadhesive tablets Bioadhesive tablets

1998-04-21

2001-06-05

Spear, James M. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Tablets, lozenges, or pills

C424S434000, C424S435000, C424S465000, C514S772300

Reexamination Certificate

active

06242004

ABSTRACT:

The invention relates to tablets having bioadhesive properties, which may be used by the transmucosal route but also, depending on their structure, by the non-transmucosal route.
Transmucosal administration has the advantage, at the metabolic level, of avoiding substantial metabolism of the active principle by the hepatic first-pass effect and hence of reducing the doses administered by improving the clinical efficacy. The active principle does not undergo the various enzymatic or chemical degradation processes along the gastro-intestinal tract, and the disadvantages associated with the function and physiology of the gastrointestinal apparatus.
Numerous formulations have been proposed for improving various properties desired for such tablets, such as bioavailability of the active principle, by controlling its rate of release and the direction of flow of active principle, or the adhesiveness of the tablet on a tissue or a mucous membrane.
In these formulations, the bioadhesive compound is frequently used in mixture with the active principle and other excipients such as swelling agents. The respective properties of these products are not, therefore, fully used to advantage. A part of the bioadhesive compound is in fact trapped in the mixture and is not used for adhesion. Similarly, not all the active principle is always used, and controlling its rate of release may prove difficult.
In other formulations, the choices made for the bioadhesive products make it necessary to use auxiliaries such as gelatin in order to obtain the desired effect.
Generally speaking, the bioadhesive tablets available at present thus have several types of limitations such as insufficient bioadhesion, excessive bulkiness, a structure lacking cohesion in use, or poor control of the intensity and/or the orientation of the flows of active principle(s).
Bioadhesive products are difficult to work industrially because they pose problems of sticking. Due to their hydrophilic nature, they are difficult to process by wet granulation; when processed in a mixture of powders they often exhibit poor flow. Finally, generally speaking, these products are not very suitable for compression.
The inventors have now found that by selecting certain types of bioadhesive compounds and excipients, it was possible to produce a new type of tablets with a succession of layers having distinct functions, and to operate by direct compression in order to produce at least one of these layers.
The object of the invention is, therefore, to provide new optimised tablets in terms of their adhesiveness and diffusion of the active principles that they contain, and hence their efficacy, and which are inexpensive.
In particular, the object is to provide tablets that may be used by the transmucosal or non-transmucosal route, and which may be administered orally if necessary.
The tablets of the invention are characterised in that they take the form of multilayers and that they contain,
at least one bioadhesive layer containing the total charge of bioadhesive material, this layer being directly compressible during the production of the tablet, and being capable of adhering to a biological tissue or a mucous membrane by impregnation with water or the biological fluid present in the environment of the tissue or of the mucous membrane, whilst permitting the release of the active principle in the desired manner, and
at least one layer containing the majority of the total charge of active principle.
It will be observed that the bioadhesive layer(s) may be compressed directly, which represents a technical advantage compared with the preparation of the bioadhesive tablets available hitherto and allows production at a lower cost.
Moreover, the total charges of active principle and of bioadhesive material are found in distinct layers respectively. Each layer may thus be produced with the minimum quantity of product required for the desired effect. This results in an economic advantage and a benefit for the patient both in medical terms and in terms of his comfort. Thanks to the concentration of the bioadhesive polymer in contact with the tissue or mucous membrane to which the tablet is applied, an intense bioadhesive effect is obtained and a controlled and reproducible release of active principle.
Optimisation of the bioadhesion of the tablets of the invention allows the production of tablets which, compared with those of the prior art, have an increased efficacy and longer period of bioadhesion for an equivalent or lower quantity of bioadhesive compound because it has been optimised. This advantage is particularly beneficial for the administration of active principles over a long period.
According to an advantageous arrangement, the tablet of the invention is characterised in that it contains, moreover, at least one layer forming a barrier to the diffusion of active principle and to the penetration of water or of said biological fluid.
Such a tablet therefore has the advantage not only of orienting the diffusion of the active principle but also of limiting the phenomena of disintegration of the matrix by protecting in particular the tablet from erosion due to the movements of neighbouring tissues (for example, the upper lip in the case of a tablet for buccal administration) by preventing inappropriate sticking of the tablet.
According to an advantageous embodiment, the bioadhesive layer of the tablets of the invention contains, in mixture with the bioadhesive material, at least one swelling agent which is insoluble, or a swelling agent which is sparingly soluble in the presence of biological fluid and/or a swelling agent which is soluble or a gelling agent which is soluble in the presence of biological fluid, with, if need be, at least one excipient capable of improving bioadhesion and/or an auxiliary which is soluble in water or acts as an agent with a hydrophilic nature.
Advantageously, the bioadhesive material is essentially composed of a polymer modified by maleic anhydride or by a derivative such as a pharmaceutically acceptable acid, ester or salt.
It is preferably a copolymer of methylvinylether and maleic anhydride.
In the context of the invention, geared to the production of multilayer structures, this polymer is in fact used as a bioadhesive in its entirety, without it being necessary, as in the prior art, to mix it with other bioadhesives and/or for it to undergo particular treatments.
Examples of copolymers of this type which are currently available on the market correspond to those marketed under the trademark Gantrez® (GAF products).
They include Gantrez® AN (anhydride form), S (acid form), ES (ester form) and MS (sodium and calcium salt).
The swelling agents which are insoluble or the swelling agents which are sparingly soluble in the presence of biological fluid are advantageously chosen from the group of cellulose ethers such as sodium carboxymethylcellulose, crosslinked hydroxypropylcellulose, high molecular weight hydroxypropylcellulose, the group of enteric and non-enteric cellulose esters, modified starches such as carboxymethyl starch, the copolymer of divinylbenzene/potassium methacrylate, the group of derivatives of methacrylic acid such as polymethylmethacrylates, the group of crospovidones/crospolyvidones, high molecular weight polyvinyl alcohol, the group of alginic acid and derivatives thereof, the group of derivatives of acrylic acid such as crosslinked acrylic acid with divinylglycol and its calcium salt, the group of carrageenans and derivatives thereof, the copolymer of vinyl acetate and crotonic acid.
Swelling agents which are soluble or gelling agents which are soluble in the presence of biological fluid suitable for the exploitation of the invention include the group of cellulose ethers such as methylcellulose, sodium carboxymethylcellulose, low molecular weight hydroxypropylmethylcellulose, the group of enteric and non-enteric cellulose esters, low molecular weight polyvinyl alcohol, medium viscosity polyvinyl alcohol, polyoxyethylene glycol, the group of povidones/polyvidones/copolyvidones, scleroglucanes, starches an

Affiliated with

Also associated with

Rating

Bioadhesive tablets does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Bioadhesive tablets, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bioadhesive tablets will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2456852