Microparticles With Modified Release of At Least One Active Principle and Oral Pharmaceutical Form Comprising Same
First Claim
1. Coated “
- reservoir”
microparticles containing at least one active principle (AP) and being of the type;
constituted by AP particles each covered with at least two different coating films,with a mean diameter of less than 2000 microns, preferably between 50 and 800 microns and even more preferentially between 100 and 600 microns;
characterized in that, in combination, the coating films are capable;
of ensuring release of the AP governed by two different triggering mechanisms, one based on a variation in pH and the other allowing the release of the AP after a predetermined residence time in the stomach,of inducing in vitro dissolution behavior (performed in a paddle dissolutest in accordance with the European Pharmacopeia 5.2 or a device of type II in US Pharmacopeia 28-NF23, maintained at 37°
C. and rotated at 100 rpm) such that;
at constant pH 1.4, the dissolution profile comprises a lag phase of adjustable duration of less than or equal to 8 hours, preferably less than or equal to 5 hours and even more preferentially between 1 and 5 hours;
the passage from pH 1.4 to pH 7.1 leads to a sustained-release phase of adjustable duration, starting without a lag time and such that t½
is between 0.25 and 20 hours, preferably between 0.25 and 12 hours, more preferably between 0.25 and 8 hours and even more preferentially between 0.25 and 4 hours, in which t½
is the time required to release 50% of at least one of the active principles contained in the coated microparticles.
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Accused Products
Abstract
The invention concerns microparticulate systems with modified release of oral active principle(s). The invention aims at providing a novel pharmaceutical with time-dependent and pH-dependent release mechanism, enabling: a) the latent period preceding the release of the active principle in the stomach; b) the pH triggering the release of the active principle in the intestine; c) the release speed of the active principle. This is achieved through the use of coated microparticles made from particles of active principle each coated with two coating films A and B. A comprises: film-forming (co)polymer (A1) insoluble in fluids of the gastrointestinal tract; ethylcellulose (co)polymer (A2) soluble in fluids of the gastrointestinal tract; plasticizing polyvinylpyrrolidone (A3); castor oil/optionally a surfactant and/or magnesium stearate lubricant (A4). B comprises a hydrophilic polymer (B1) bearing ionized groups with neutral pH (EUDRAGIT® L100-55) and a hydrophobic compound (B2) (LUBRITAB®). The invention also concerns medicines based on said microparticles.
185 Citations
24 Claims
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1. Coated “
- reservoir”
microparticles containing at least one active principle (AP) and being of the type;constituted by AP particles each covered with at least two different coating films, with a mean diameter of less than 2000 microns, preferably between 50 and 800 microns and even more preferentially between 100 and 600 microns; characterized in that, in combination, the coating films are capable; of ensuring release of the AP governed by two different triggering mechanisms, one based on a variation in pH and the other allowing the release of the AP after a predetermined residence time in the stomach, of inducing in vitro dissolution behavior (performed in a paddle dissolutest in accordance with the European Pharmacopeia 5.2 or a device of type II in US Pharmacopeia 28-NF23, maintained at 37°
C. and rotated at 100 rpm) such that;at constant pH 1.4, the dissolution profile comprises a lag phase of adjustable duration of less than or equal to 8 hours, preferably less than or equal to 5 hours and even more preferentially between 1 and 5 hours; the passage from pH 1.4 to pH 7.1 leads to a sustained-release phase of adjustable duration, starting without a lag time and such that t½
is between 0.25 and 20 hours, preferably between 0.25 and 12 hours, more preferably between 0.25 and 8 hours and even more preferentially between 0.25 and 4 hours, in which t½
is the time required to release 50% of at least one of the active principles contained in the coated microparticles.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
- reservoir”
Specification