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

Microparticulate oral pharmaceutical dosage form for the delayed and controlled release of at least one active principle (AP)—excluding perindopril—this active principle having an absorption window in vivo that is essentially limited to the upper parts of the gastrointestinal tract,

• wherein the dosage form comprises “reservoir” microcapsules of active principle, each coated with one single, composite coating film,
• wherein the single, composite coating film comprises at least one hydrophilic polymer A carrying groups that are ionized at neutral pH, and at least one hydrophobic compound B;
• wherein the at least one hydrophobic compound B is selected from the group consisting of hydrogenated vegetable oils, vegetable waxes, wax yellow, wax white, wax microcrystalline, lanolin, anhydrous milk fat, hard fat suppository base, lauroyl macrogolglycerides, cetyl alcohol, polyglyceryl diisostearate, diester or triester of glycerol with at least one fatty acid and mixtures thereof;
• wherein the microcapsules have a diameter of between 200 and 800 microns;
• wherein the weight ratio B/A is between 0.5 and 1.5;
• wherein the release of the active principle is governed by two different triggering mechanisms,
• wherein the first triggering mechanism releases the at least one active principle based on a variation in pH,
• wherein the second triggering mechanism releases the at least one active principle after a predetermined residence time in the stomach,
• wherein the dissolution behavior of the pharmaceutical dosage in vitro is such that:
• at a constant pH of 1.4, the dissolution profile includes a latency phase with a duration less than or equal to 5 hours, and a controlled release phase following the latency phase such that the release time for 50% of the active principle (t1/2) is between 0.5 hour and 35 hours, and
• the change from pH 1.4 to pH 6.8 results in a release phase that starts without a latency period.