MXPA99002918A - Oral preparation containing at least one active pharmaceutical substance in a matrix capable of swelling in an aqueous medium - Google Patents

Oral preparation containing at least one active pharmaceutical substance in a matrix capable of swelling in an aqueous medium

Info

Publication number
MXPA99002918A
MXPA99002918A MXPA/A/1999/002918A MX9902918A MXPA99002918A MX PA99002918 A MXPA99002918 A MX PA99002918A MX 9902918 A MX9902918 A MX 9902918A MX PA99002918 A MXPA99002918 A MX PA99002918A
Authority
MX
Mexico
Prior art keywords
matrix
layer
aqueous medium
active substance
swelling
Prior art date
Application number
MXPA/A/1999/002918A
Other languages
Spanish (es)
Inventor
Cremer Karsten
Original Assignee
Lts Lohmann Therapiesysteme Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lts Lohmann Therapiesysteme Gmbh filed Critical Lts Lohmann Therapiesysteme Gmbh
Publication of MXPA99002918A publication Critical patent/MXPA99002918A/en

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Abstract

An oral preparation contains in a matrix capable of swelling in an aqueous medium at least one active pharmaceutical substance which is released in the aqueous medium when the matrix swells therein, in a retarded manner, while the matrix is largely resistant to decomposition during the release process. The preparation is characterised in that it consists of a stratified tablet with layers which adhere onto each other and of which at least one layer is the swellable matrix layer and at least another layer is an auxiliary and/or substrate layer. The swellable matrix layer contains a certain proportion of cross-linked amylose.

Description

ORAL PREPARATION, WHICH CONTAINS AT LEAST ONE PHARMACEUTICAL ACTIVE SUBSTANCE, IN A HINCHABLE MATRIX IN HALF AQUEOUS DESCRIPTION OF THE INVENTION The invention relates to an oral preparation, containing at least one pharmaceutical substance, in a swellable matrix in aqueous medium. , which is released in a delayed manner to the aqueous medium from the matrix, while the latter remains resistant to disintegration. The delayed release of active substance from peroral administration forms serves to avoid unwanted fluctuations in the plasma level. Among the variants of configuration that allow a delayed release of active substance are also the tablets of layers, especially those in which the surface of the layer that has the active substance becomes greater as the release occurs. , with which the speed of release can be controlled, so that it remains largely constant. This increase in surface area can be, according to the design and recipe of the layered tablet, the result of the continuous erosion of one or several contiguous layers or of the expansion of the layer containing the active substance. The principle mentioned at the beginning is described in documents P 4341442.7 and P 44 16926.4 and the one mentioned in the second place is described for example in US 5,422,123. When examining the tablets in layers with inflatable matrix layer - existing in the market, it was possible to check only a satisfactory increase of the surface by swelling can be obtained avoiding in great part a mechanical solicitation of the tablet. When the swelling occurs, due to the entrance of the aqueous medium, a semi-solid gel, ref. 29190 with volume increase, which has a lower mechanical stability. In the disintegration test according to DAB 10 with plexiblas plate, an important loss of the swollen tablets occurs. The cause of the absence of mechanical stability in these swollen matrix layers is that inflatable polymers are used, which produce an expansion. These are mainly strongly hydrophilic, in soluble or slowly dissolving polymers due to transverse cross-linking, the formation of crystalline regions or their large chain length. As an example of these types of polymers may be mentioned; croscarmek) sa, polyvinyl alcohol with a high degree of hydrolix and hydroxypropylmethylcelluloses with a high molecular weight. These highly expandable polymers are also used due to this property, as accelerators of the disintegration or - explosive agents in recipes for tablets (Sucker et al., Pharmaceutical Technology, Thieme Verlag, 1991, page 174 and following). The manufacture of inflatable matrices, which also retain their mechanical stability in aqueous medium, after having sufficiently swelled, is extremely -problematic if the aforementioned polymers are used, since their properties favorable to expansion can not be separated from the characteristics- encourage disintegration. Accordingly, what is intended with the present invention is to provide a peroral preparation, with an inflatable matrix in contact with an aqueous medium, which releases active substance in a delayed manner to the aqueous medium and remains mechanically stable and resistant to the disintegration, in the state expended, until the liberation ends, to a large extent. This problem is solved, according to the invention, with a preparation of the type mentioned in the main term of claim 1, with the characteristics of the main claim. The cross-cross amylose expands in water, although it differs from the usual swellable polymers in its surprisingly high mechanical strength in the expanded state. In this way, it is possible to create for the first time tablets in layers, highly improved and resistant to disintegration, in which the superficial increase of the expandable layer of the matrix is still effective when mechanical stresses occur, as for example in the disintegration test or after the application in the gastrointestinal tract. The amylosa is a component of natural starches, which is found in the interior of starch grains, with an approximate content of 15 to 30%, and is formed by unbranched chains with D-glucopyranose blocks joined together with glycosidic bond a- ?, 4. When reacting with agents such as, for example, epichlorohydrin-2,3-dibromopropanol, amylose can be cross-linked efficiently, for which a quantitative proportion of 0.1 to 10% is necessary cross-linking crosslinker, referred to amylose. From US Pat. No. 5,456,921, it is known that cross-linked amylose, in particular that having a relatively low degree of crosslinking, is characterized in particular by its strong tendency to the formation of hydrogen-bridge bonds between the chains or lectors, which produces high cohesion forces, which can maintain the dynamic stability of a preparation or of a tablet, even when it is swollen. In this patent, there are also described several homogeneous, ie, single-layer, cross-linked amylose compresses, which release their active substance in a delayed and uniform manner, for example theophylline. It deals with several types of mechanisms to control the rate of release, and one of them is favored, which controls the kinetics of water access through intermolecular hydrogen bridge-links, which is considered of great importance for the release speed. Surprisingly, it has been achieved for the first time, with the invention, that the tablets in layers, with at least one inflatable matrix layer, whose release kinetics can be controlled by the surface increase of the matrix layer by swelling, possess, with a certain amylose content, a mechanical resistance much higher than the state of the technique, which guarantees a reliable control of the release kinetics, even in the case of mechanical stress of the tablet, since its surface increase is It is carried out in spite of this effort, without disintegrating when liberation takes place. The term "layer tablet", in the sense of the present invention refers to a tablet formed by at least two layers adhered to each other and obtained by compression of powder or granules. A layer compressor may also possess other features, such as for example a coating based on a composition containing sugar or polymer or an envelope generated by compression of powder or granules. In this case, the layered tablet could also be referred to as lamellar or coated tablet. The layered tablet, defined in the characterizing part of claim 1, has a matrix layer containing active substance, this term constituting "the superior rank designation of all - the layered compositions in which it is distributed or incorporated - uniformly an active substance A layer tablet according to the invention may also have more than one matrix layer with active substance, such as, for example, when it comes to delayed release of an active substance, or several components of active substance, at high speed Accordingly, a layered tablet according to the invention can contain one or more active substances.The matrix layer containing the active substance can swell when the aqueous medium enters, ie when it comes into contact with water - with gastric or intestinal juices, physiological or artificial, the matrix-layer absorbs water, with volume increase as optionally - the components dissolved in the water, with the particularity that large part of the swelling water is typically stored between the polymer chains contained in the preparation of the matrix. A wide resistance to the disintegration of the matrix layer during the release process means, in the sense of the invention, that the disaggregation in the test according to DAB 10 does not end until at least the greater part of the dose of active substance has been released with the matrix layer. The delayed release of active substance usually occurs for at least several hours, which does not rule out any type of release profile, such as linear and non-linear and also complex profiles with an initial dose and maintenance , etc. The layered tablet according to the invention and the main claim is distinguished from the layered tablets known in the state of the art, by the fact that they have an inflatable matrix with a content of transversely crosslinked amides. The preferential contents of cross-linked amylose cross-linked in the matrix layer oscillate between 30 and 99.5%. While the very low dosage active substances allow a high cross-linked amylose content, the higher doses of active substance require, taking into account the maximum size of the tablet, a more or less significant reduction in the content of the auxiliary substance. In order that the described positive effects of cross-linked amylose can be developed, a content of at least 20% is generally to be used. Lower quantities are not so appreciated, although they also correspond -to the invention, since due to the choice of technical-pharmaceutical measures- additional special, such as the use of special forms of particles and granulometric distributions, special conditions of compression, of agglomeration etc. can also be achieved by compressing them in layers according to the invention. The essential advantage of a preparation according to the invention therefore lies in the fact that a layered tablet produced in this way maintains its content in the gastrointestinal tract independently of the mechanical running force and thus allows a delayed and uniform release of the content of its active substance until exhaustion. It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims (6)

  1. CLAIMS Having described the invention ^ as. The property contained in the following claims is claimed as property: 1.- Oral preparation containing, in an inflatable matrix in aqueous medium, at least one pharmaceutical active substance that is released - in a delayed manner in the aqueous medium, from the matrix, when swelling it, while said matrix remains largely resistant to disintegration during the release process, which is characterized by the fact that it is a tablet in layers, with layers adhered to each other, one of the - which at least is the inflatable matrix layer and at least one other auxiliary layer and / or support, and the inflatable matrix layer contains a certain proportion of transversely cross-linked amylose.
  2. 2. Preparation according to claim 1, characterized in that the proportion of cross-linked amylose cross-linked in the matrix layer ranges from 20 to 99.5% by weight.
  3. 3. Preparation according to claim 1, characterized by the fact that the rate of release remains practically constant during most of the period of release.
  4. 4. Preparation according to claim 1, characterized in that it contains more than one active substance.
  5. 5. Preparation according to one of claims 1 to 4, characterized in that the layer or layers adjacent to the inflatable matrix layer is / are largely resistant to disintegration during the treatment of the active substance.
  6. 6. Preparation according to one or more of claims 1 to 5, characterized in that it has been configured as a core of a sheet or coated tablet.
MXPA/A/1999/002918A 1996-09-28 1999-03-26 Oral preparation containing at least one active pharmaceutical substance in a matrix capable of swelling in an aqueous medium MXPA99002918A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19640062.7 1996-09-28

Publications (1)

Publication Number Publication Date
MXPA99002918A true MXPA99002918A (en) 2000-05-01

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