Matrix compositions for controlled delivery of drug substances

Abstract

A novel matrix composition for pharmaceutical use. The matrix composition has been designed so that it is especially suitable in those situation where an improved bioavailability is desired and / or in those situation where a slightly or insoluble active substance is employed. Accordingly, a controlled release pharmaceutical composition for oral use is provided in the form of a coated matrix composition, the matrix composition comprising i) a mixture of a first and a second polymer that have plasticizing properties and which have melting points or melting intervals of a temperature of at the most 200° C., the first polymer being selected from the group consisting of polyethylene glycols and polyethylene oxides, and the second polymer being selected form block copolymer of ethylene oxide and propylene oxide including poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide-polypropylene oxide (PEO-PPO), ii) a therapeutically, prophylactically and / or diagnostically active substance, the matrix composition being provided with a coating having at least one opening exposing at one surface of said matrix, wherein the active substance is released with a substantially zero order release.

Description

FIELD OF THE INVENTION[0001]The present invention relates to novel matrix compositions that are suitable for use in the pharmaceutical field especially for delivery of one or more active substance after oral administration.BACKGROUND OF THE INVENTION[0002]During the last decades many different systems for modifying the release of an active drug substance from a pharmaceutical composition have been developed. Most of them aim at obtaining a zero of a first order release rate of the active substance from the composition. Zero order release rate (i.e. constant release of the active substance with time) seems to be very difficult to obtain from a pharmaceutical composition. The present invention is based on a polymeric matrix composition, which is construed to deliver the active substance in a zero order release manner. The present invention is a further development based on the Applicant's previously described drug delivery systems, see e.g. EP-B-0 406 315, EP-B-0 493 513, EP-B-0 740 3...

AI Technical Summary

Benefits of technology

[0004]For controlled release formulation solid dispersions or solid solutions offer an attractive means of increasing the solubility, and therefore, potentially, increasing the oral bioavailability of different compounds. There are several potential mechanisms by which a solid dispersion may lead to dissolution enhancement. These can be classified as a) reduction in the drug particle size, 2) changes in the surface characteristics of the drug particles to improve wet ability, and 3) formation of a higher energy solid state form (e.g. amorphous) of the active ingredient.

[0005]Accordingly, the primary reason to develop a solid molecular dispersion (amorphous form) is to enhance dissolution and improve the oral bioavailability of a poorly water-soluble drug. However, the re-crystallization of amorphous solids, their greater hygroscopicity, and their reactivity can cause difficulties in developing stable compositions. The increase in water uptake results from the ability of amorphous solids to absorb water into their internal structure, as opposed to the surface adsorption shown by denser crystalline compounds. Accordingly, in some circumstances it can be an advantage to be able to control the degree of amorphous material in the solid composition relative to the crystalline phase and at the same time obtain the desired release pattern of the formulation. With the desired release pattern according to the invention is meant controlled release such as zero order release, pulsatile or burst releases as well as immediate release.

[0006]According to the present invention a specific combination of PEO and a block copolymer such as poloxamer has shown to enable the control of amorphous and / or amorphous / crystalline phase and controlled release of an active substance from the polymer matrix system.

Problems solved by technology

Zero order release rate (i.e. constant release of the active substance with time) seems to be very difficult to obtain from a pharmaceutical composition.

However, one of the challenges that still need to be solved is to provide pharmaceutical compositions for e.g. slightly soluble drug substances, wherein the pharmaceutical composition after oral administration leads to an improved bioavailability compared to known compositions.

It is well known that changing a crystalline compound into its amorphous state will substantially increase the aqueous solubility of the compound.

However, the amorphous form is normally not a thermodynamically stable form and, accordingly, precipitation of the crystalline form may occur during storage.

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