Modified starch derivative-based matrix for colon targeting

摘要

A controlled-release oral pharmaceutical composition of at least an active agent, including: a) a lipophilic matrix consisting of lipophilic compounds and/or amphiphilic compounds; and b) an hydrophilic matrix, wherein the hydrophilic matrix includes at least an indigestible polysaccharide, the active ingredient being dispersed in the lipophilic and/or the hydrophilic matrix.;The present invention also relates to a process for the preparation of such a pharmaceutical composition.

主权项

1. An oral pharmaceutical composition of at least an active agent for controlled release in the colon of a subject suffering from an inflammatory bowel disease, comprising:
a compressed mixture of: a lipophilic matrix consisting of lipophilic compounds and/or amphiphilic compounds, an hydrophilic matrix comprising at least a branched maltodextrin or dextrin having between 15 and 50% of 1→6 glucoside linkages, a reducing sugar content of less than 20%, a polymolecularity index of less than 5, and a number-average molecular mass Mn at most equal to 4500 g/mol, and an active ingredient, said active ingredient being dispersed in the lipophilic matrix, the hydrophilic matrix, and throughout said compressed mixture, wherein the compressed mixture is prepared by a process that embeds said active ingredient, at least in part, in the lipophilic matrix and is selected from the group consisting of:
(i) a direct compression process comprising blending the active ingredient, the hydrophilic matrix and lipophilic matrix to form a mixture, compressing the mixture, and curing the mixture,(ii) a partial melt granulation and compression process comprising forming a melt granulation from the active ingredient, the hydrophilic matrix and a part of the lipophilic matrix, blending the melt granulation with a remaining part of the lipophilic matrix to form a mixture, and compressing the mixture, and, optionally, curing the compressed mixture,(iii) a separate melt granulation and compression comprising forming a first melt granulation from the hydrophilic matrix and part of the lipophilic matrix, forming a second melt granulation from the active and a remaining part of the lipophilic matrix, blending the first melt granulation and second melt granulation to form a mixture, and compressing the mixture, and, optionally, curing the mixture, and(iv) a melt granulation and compression process comprising forming a mixture from a melt granulation of the active ingredient, the hydrophilic matrix, and the lipophilic matrix, and compressing the mixture, and, optionally, curing the compressed mixture, and wherein the composition is coated or uncoated, and the combination of the lipophilic matrix and the hydrophilic matrix provides a controlled release of the active ingredient into the colon of the subject.