Use of a mixture of two or more enteric materials to regulate drug release via membrane or matrix for systemic therapeutics
View Patent ↗Disclosed are pharmaceutical compositions, particularly oral dosage forms, which comprise two or more enteric coating materials, either as a coating or as part of a matrix dosage form, and methods of making and using the same. The compositions are characterized by having a sustained release profile at lower pH and an accelerated dissolution profile at higher pH.
1. A pharmaceutical composition, comprising:
(a) a core containing one or more pharmaceutically active ingredients selected from one or more of psychotropics, anti-depressants, anti-manics, antiparkinsonian substances, agents for the treatment of hyperactivity or attention deficit hyperactivity disorders, stimulants, sedatives, anticonvulsants, and antispasmodics, and
(b) a coating layer surrounding the core, said coating layer comprising a combination of three or more enteric coating materials selected from the group consisting of cellulose acetate phthalate; hydroxypropyl methylcellulose phthalate; polyvinyl acetate phthalate; hydroxypropyl methylcellulose acetate succinate; cellulose acetate trimellitate; copolymer of methylvinyl ether and maleic anhydride; zein; methacrylic acid copolymers; acrylate copolymers; hydroxypropyl methylcellulose phthalate/poly(methacrylic acid-co-methyl methacrylate 1:1/poly(methacrylic acid-co-methyl methacrylate) 1:2; hydroxypropyl methylcellulose phthalate/cellulose acetate phthalate/poly(methacrylic acid-co-methyl methacrylate) 1:2; hydroxypropyl methylcellulose phthalate/cellulose acetate phthalate/poly(methacrylic acid-co-methyl methacrylate 1:1/poly(methacrylic acid-co-methyl methacrylate) 1:2; polyvinyl acetate phthalate/cellulose acetate trimellitate/zein/poly(methacrylic acid-co-methyl methacrylate) 1:2, at least two of which enteric coating materials dissolve at a different pH in the small intestine,
wherein the active ingredient(s) has a release profile that is pH-dependent,
wherein the release profile is at first sustained while the composition is in a part of the small intestine of a first pH and then accelerated when the composition is in a part of the small intestine of a second pH, and wherein said first pH is lower than said second pH, and
wherein more than 70% of the active ingredient(s) is dissolved prior to entering the large intestine.
2. The pharmaceutical composition of claim 1 , wherein the coating layer comprises three or more enteric coating materials each of which dissolves at a different pH.
3. The pharmaceutical composition of claim 1 , wherein the coating layer also comprises a plasticizer and/or a colorant.
4. The formulation of claim 1 , wherein said coating layer additionally comprises a sustained release coating material.
5. The pharmaceutical composition of claim 1 , wherein the oral dosage form is a tablet, a capsule, beads, beadlets or sachet.
6. The pharmaceutical composition of claim 1 , wherein the active pharmaceutical ingredient is one or more of morphine sulfate, oxycodone, amphetamine, methylphenidate, guanfacine, alprazolam, carbamazepine, and levodopa/carbidopa.
7. A method of treating a CNS condition in a mammal, comprising administering to a mammal in need thereof an oral dosage form according to claim 1 .
8. The method of claim 7 , wherein the mammal is a human.
9. A pharmaceutical composition, comprising:
(a) a core containing one or more pharmaceutically active ingredients selected from one or more of psychotropics, anti-depressants, anti-manics, antiparkinsonian substances, agents for the treatment of hyperactivity or attention deficit hyperactivity disorders, stimulants, sedatives, anticonvulsants, and antispasmodics, and
(b) a coating layer surrounding the core, said coating layer comprising:
(i) a combination of two or more enteric coating materials selected from the group consisting of cellulose acetate phthalate; hydroxypropyl methylcellulose phthalate; polyvinyl acetate phthalate; hydroxypropyl methylcellulose acetate succinate; cellulose acetate trimellitate; copolymer of methylvinyl ether and maleic anhydride; zein; methacrylic acid copolymers; acrylate copolymers; hydroxypropyl methylcellulose phthalate/poly(methacrylic acid-co-methyl methacrylate 1:1/poly(methacrylic acid-co-methyl methacrylate) 1:2; hydroxypropyl methylcellulose phthalate/cellulose acetate phthalate/poly(methacrylic acid-co-methyl methacrylate) 1:2; hydroxypropyl methylcellulose phthalate/cellulose acetate phthalate/poly(methacrylic acid-co-methyl methacrylate 1:1/poly(methacrylic acid-co-methyl methacrylate) 1:2; polyvinyl acetate phthalate/cellulose acetate trimellitate/zein/poly(methacrylic acid-co-methyl methacrylate) 1:2, at least two of which enteric coating materials dissolve at a different pH, and
(ii) a sustained release coating material,
wherein the active ingredient(s) has a release profile that is pH-dependent,
wherein the release profile is at first sustained while the composition is in a part of the small intestine of a first pH and then accelerated when the composition is in a part of the small intestine of a second pH, and wherein said first pH is lower than said second pH, and
wherein more than 70% of the active ingredient(s) is dissolved prior to entering the large intestine.
10. A method of treating a CNS condition in a mammal, comprising administering to a mammal in need thereof an oral dosage form according to claim 9 .
11. The method of claim 10 , wherein the mammal is a human.
12. The pharmaceutical composition of claim 1 , wherein the first pH is between 5.0-6.5.
13. The pharmaceutical composition of claim 1 , wherein the second pH is between 6.0-7.5.