Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1998-06-30
2000-12-19
Spear, James M.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424451, 424462, 424464, 424469, 424470, 424489, 424490, 424497, A61K 920, A61K 926, A61K 954, A61K 958
Patent
active
061624659
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention broadly relates to the field of so called multiple unit systems, especially but not exclusively pharmaceutical formulations designed as multiple unit dosage forms. More specifically, the invention relates to a method for determining characteristics on dose-level of multiple unit systems, such as dose-level properties relating to the release rate or release profile of one or more active substances. Other aspects of the invention relates to an industrial process for the manufacture of multiple unit system formulations, including such a method, and to the use of the method in a process for designing a multiple unit system formulation product.
The present invention is especially useful in connection with in vitro dissolution tests on drug products where the therapeutic performance of drugs is highly dependent on the drug dissolution properties. Therefore, the technical background of the invention and objects and embodiments thereof, will be described with reference to such dissolution tests. However, the invention may also be applicable in connection with tests on other industrial products than pharmaceutical drugs, such as food industry products. The invention may also be implemented by the use of non-destructive tests.
BACKGROUND
Pharmaceutical formulations can be designed as Multiple Unit Systems, an example of which is the so called MUPS (Multiple Unit Pellet Systems), where a dose is administrated for example as a tablet (tableted dosage form) or as a capsule (capsulated dosage form), each dose comprising a plurality of individual pellets or granules, referred to as subunits in the following. Each subunit carries one or more active drug or substance. A typical number of subunits in one dose form is 50, 100, 1000 or more.
Prior art discloses many different types of units intended for MUPS, such as for instance those described in U.S. Pat. No. 5,085,868. Usually, this type of formulation is preferred for controlled or sustained release formulations as well as for enteric coated formulations. The dose of the active substance may be administrated in the form of a tablet or a capsule or a like which disintegrates to make available a multitude of coated subunits, which release the active substance during the dissolution. Other prior-art MUPS are disclosed in U.S. Pat. No. 4,957,745, U.S. Pat. No. 4,927,640, U.S. Pat. No. 4,994,260, and U.S. Pat. No. 5,085,868.
Today, the common test procedure for determining the content, the functionality and/or the quality, etc. of MUPS is to analyze the formulation on a dose-level, i.e. to perform the analysis on a whole tablet or capsule. In conventional methods for determining the dose-level release profile the dosage form is placed in a test solution (in vitro testing) under controlled conditions, whereupon the test solution containing the dissolved active substance is analysed, typically by determining a release profile by the use of an optical absorption measurement.
However, MUPS are characterised in that the dose is the summation of the individual subunits and, therefore, by such prior-art test methods for analysing properties on dose-level of MUPS one only obtains a measurement of the cumulative release property of the entire subunit population. Variations in structure and release property between the individual subunits are not detectable, such as variations in film thickness, film defects, uneven subunit surfaces, deviations from spherical form of some subunits, etc. As a result, with presently available MUPS test methods it is not possible to identify the exact causes leading to unintended or intended variations on dose-level, such as variations in the release profile. Thus, even if it is possible to identify an "error" in the test results obtained by the conventional dose-level test methods, these methods will limit the possibilities to measure the product quality in terms of process parameters, i.e. the possibility to achieve detailed information is limited.
Dissolution testing provides essential information for th
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Folestad Staffan
Gottfries Johan
Ostling Goran
Torstensson Arne
Zackrisson Gunnar
Astra Aktiebolag
Spear James M.
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