Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active component

Abstract

The invention relates to a microparticulate system for the delayed and controlled release of active principles (AP) whose absorption window in vivo is essentially limited to the upper parts of the gastrointestinal tract, this system being intended for oral administration. The object of the invention is to provide a system ensuring that the AP is released with certainty by means of a dual mechanism of 'time-dependent' and 'pHdependent' release. To achieve this object, the invention proposes a multimicrocapsular oral galenical form which is designed so as to guarantee therapeutic efficacy, and in which the release of the AP is governed by a dual release triggering mechanism that is 'timetriggering' and 'pH-triggering'. This system comprises of microcapsules (200 to 600 mu m) comprising a core of AP coated with a film (maximum 40% by weight) comprising a hydrophilic polymer A (Eudragit<(R)> L) and a hydrophobic compound B (vegetable wax, melting point = 40-90 DEG C), B / A being between 0.2 and 1.5. These microcapsules have a dissolution behavior in vitro such that, at a constant pH of 1.4, a latency phase of between 1 and 5 hours is observed, followed by a release of the AP, and such that the change from pH 1.4 to pH 6.8 results in a release of the AP without a latency period in vitro.

Description

This application is a continuation-in-part of Application No. 10 / 492,129, the national phase of International Application No. PCT / FR02 / 03443 filed on October 9, 2002, and claiming the October 2001 Application No. FR01 / 12999 filed on 9th, the above applications are incorporated by reference. technical field The present invention relates to the field of microparticle systems for delayed and controlled release of one or more active ingredients AP, intended for oral administration. Background technique The active ingredients referred to in the present invention are those whose absorption is substantially limited to the upper part of the gastrointestinal tract upstream of the colon (upstream of the ileal junction) and which represent the majority of pharmaceutical activity. More precisely, the present invention relates to microparticulate galenic formulations for delayed and controlled release, wherein the controlled release phase is unmistakably triggered by a double mechanis...

AI Technical Summary

Problems solved by technology

Finally, the formulation of EP-A-1 101 490 does not resolve inter- or intra-individual ambiguities in gastric residence time

Thus, the prior art does not include galenic systems which delay and ensure the release of the active ingredient preferably absorbed in the upper part of the gastrointestinal tract by means of a dual release mechanism as follows:

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