Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2001-01-04
2003-10-21
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S469000, C424S490000
Reexamination Certificate
active
06635276
ABSTRACT:
This application is a 371 of PCT/EP99/03110 filed May 6, 1999.
BACKGROUND OF THE INVENTION
The invention relates to an active ingredient-containing oral or mucosal preparation with controllable active ingredient release rate and its use.
Oral dosage forms ordinarily deliver their active ingredient by diffusion or disintegration, resulting in nonlinear release kinetics. A frequent requirement for oral pharmaceutical systems is that there be linear zero order active ingredient release from the administration form. It may additionally be desirable to be able to modulate as desired the release profile appropriate for specific requirements. Systems which achieve the desired effect are normally complicated and costly to produce.
Description of the Prior Art
The document U.S. Pat. No. 4,606,909 describes a pharmaceutical preparation for oral administration having a homogeneous core in an internal covering which is insoluble at pH below 7.5 but is soluble in the small bowel region, the material of the covering being selected from a group of acrylic polymers and each core consisting of a multiparticulate system of particles with an average size between 1 and 10 &mgr;m and the particles containing an active substance of low solubility.
WO 89/03437 describes a diffusion-controlled, multiparticulate oral formulation with active ingredient-containing individual units which are provided with a water-insoluble but water-diffusible covering comprising a combination of a water-dispersible film former and a polymeric substance to prevent adhesion of the units at elevated temperature, which imparts a certain flowability to the units. The covering has adequate plastic deformability which prevents a significant change in the release behaviour of the active ingredient from compressed or noncompressed units.
SUMMARY OF THE INVENTION
DE 39 18 801 A1 describes a product with controlled active ingredient delivery, which consists of multiparticulate articles having at least one active ingredient and at least one inactive component which controls the rate of active ingredient release and which comprises two to four layers. The invention in this case consists of the facts that
a) the innermost layer consists of an inactive core or is identical to the outwardly following one,
b) the outwardly following layer consists of active ingredient and possibly additionally of inactive component which is unsuitable in terms of nature or quantity for significantly controlling active ingredient release,
c) the following layer contains the highest proportion of inactive component which controls the rate of release, and additionally solid ingredients of the nature of a matrix, and controls the rate, and
d) possibly a further layer follows and controls rapid release of the active ingredient at the start but has a negligible effect on the rate of release.
The invention is based on the object of indicating an administration form for an active ingredient-containing oral or mucosal preparation which is less complicated and displays, using simple and cost-effective means, release kinetics which can be modulated as desired.
The object is achieved with an active ingredient-containing oral or mucosal preparation having a controllable active ingredient release rate of the type specified in the preamble of claim
1
by a configuration corresponding to the features indicated in claim
1
.
The following definitions serve to explain the invention:
Preparation: A composition containing a first group of particles and at least one further group of particles which is not identical to the first group of particles.
Particles: By this are meant spherical and nonspherical particles with a size in the region above 10 &mgr;m. The upper limit of particle size is in principle not fixed, but for the intended purpose of use in the pharmaceutical or veterinary sector upper limits of 3 mm are preferred. The particles comprise a core and a covering which completely envelopes the core and which may also be referred to as coating layer. In a particular embodiment, the core of the particles may also be coated with more than one coating layer.
Core: The core is a spherical or nonspherical particle with a size in the region above 1 &mgr;m. The upper limit of the size of the core is in principle not fixed, but for the intended purpose of use in the pharmaceutical or veterinary sector an upper limit of 2 mm is preferred. Cores with sizes between 10 and 50 &mgr;m are preferred. The core contains a core substance and at least one active ingredient.
Coating layer: The coating layer covers the core of the particles completely. In the case of spherical cores, the coating layer has the shape of a hollow sphere. The coating layer or coating layers may likewise in principle be of any thickness. The thickness of the coating layer corresponds to the size of the particles minus the size of the core divided by 2. In the case of spherical particles with spherical cores, the thickness of the coating layer(s) corresponds to the radius of the particles minus the radius of the core. There is in principle no restriction on the thickness of the coating layer, that is to say there is in principle no upper limit. However, the thickness of the coating layer for a specific core is always essentially constant. For the intended pharmaceutical purposes, however, covering thicknesses between 10 and 1000 &mgr;m are preferred. Covering thicknesses between 10 and 100 &mgr;m are particularly preferred. The coating layer contains a coating substance and is essentially free of the active ingredient which is present in the core.
Group: A plurality of identical particles forms a group of particles. This means that all the particles in this group have the same uniform size of the core and the same uniform coating layer. Moreover, all the other properties of the particles which belong to a group of particles are essentially the same. The consequence of this is that a single group of particles accordingly shows in a particular medium a characteristic release behaviour for the active ingredient(s).
It is advantageous in the case of particles with identical core substance and identical covering substance, these necessarily being assigned to different groups according to the relative proportions by weight of core substance and covering substance, and identical groups displaying identical erosion and release behaviour, to make use of the possibility resulting therefrom for controlling the release kinetics of the active ingredient. This control is exerted via the mixing ratio of different groups of particles. For example, it is possible to select individual groups which differ from one another by a stepwise delay in the start of release. When groups of this type are combined in such a way that, for example, they start to release active ingredient sequentially at equal time intervals it is possible to control any desired course of active ingredient release or modulate as desired the time profile of release in accordance with specific requirements. This means that the composition according to the invention with controllable active ingredient release rate complies with the requirement that it is able to have release kinetics which can be modulated as desired using simple and cost-effective means. This is achieved without difficulty by any desired mixing ratio of the different groups of particles
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Embodiments of the invention are provided in accordance with the dependent claims. Different particles may contain different active ingredients. However, it is also possible for different particles to contain active ingredients in different concentrations. A further possibility is for cores of different particles to differ in size or mass and/or composition of their active ingredient-containing substance. In addition to this, it may be particularly advantageous that the active ingredient-containing cores are soluble or insoluble, erodable or substantially non-erodable in the gastrointestinal tract.
Carrier substrate: By this is meant a substance which is able to take up
Hochberg D. Peter
KTS Kignabb Therapie-Systeme AG
Mellino Sean
Spear James M.
Vieyra Katherine R.
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