FORMULATIONS OF MAZINDOL
Formulations of mazindol having superior stability and methods of administering same are provided. The formulations may be immediate, enhanced, or otherwise delayed release formulations of mazindol.
1 . A modified release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient, at least one release controlling polymer selected from pH-dependent polymers and pH-independent polymers, and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation.
2 . The formulation of claim 1 comprising: a first mazindol-containing component selected from an extended release component and a delayed release component and a second mazindol-containing component selected from an immediate release component, an extended release component and a delayed release component, wherein each delayed release component comprises from 5% to 99% by weight of the formulation of at least one pH-dependent polymer and said extended release component comprises from 5% to 99% by weight of the formulation of a pH-independent polymer.
3 . The formulation of claim 1 for once-a-day administration or twice-a-day administration.
4 . The formulation of claim 1 comprising from 0.1 mg to 20 mg of mazindol.
5 . The formulation of claim 1 , wherein said first component comprises a plurality of the delayed release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets, extended release pellets and delayed release pellets, wherein said delayed release pellets comprise an immediate release core or an extended release core coated with a delayed release coating, and said extended release pellet comprises an extended release core or an immediate release core coated with a layer of a pH-independent polymer.
6 . The formulation of claim 2 , wherein said first component comprises a plurality of the extended release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets and extended release pellets.
7 . The formulation of claim 2 , wherein said first component comprises a mazindol-containing core coated with a delayed release coating, and said second component comprises an immediate release drug layer or an extended release drug layer coated on top of the delayed release coating.
8 . The formulation of claim 7 , wherein said mazindol-containing core is an immediate release core or an extended release core.
9 . The formulation of claim 8 , wherein said extended release core comprises an immediate release core coated with a coating of the pH-independent polymer or mazindol admixed with at least one pH-independent polymer.
10 . The formulation of claim 7 , wherein said second component further comprises a coating of the pH-independent polymer on top of the immediate release drug layer.
11 . The formulation of claim 7 , wherein said extended release drug layer comprises mazindol admixed with at least one pH-independent polymer.
12 . The formulation of claim 1 comprising an osmotic core comprising mazindol and at least one pharmaceutically acceptable excipient, and a semipermeable rate-controlling membrane immediately surrounding said core.
13 . The formulation of claim 12 additionally comprising a mazindol-containing layer on top of the semipermeable rate-controlling membrane.
14 . The formulation of claim 13 , wherein said mazindol-containing layer is of an immediate release, extended release or delayed release.
15 . The formulation of claim 1 additionally comprising a stabilizer selected from an acidifying agent or a hydrophobizing agent.
16 . The formulation of claim 2 , wherein at least one excipient is a low-moisture excipient selected from bulking agents, fillers, lubricants, wetting and solubility enhancing agents and dispersants.
17 . The formulation of claim 1 , wherein said pH-dependent polymer is selected from a group consisting of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly(methacrylic acid-co-methyl methacrylate), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, shellac, and zein.
18 . The formulation of claim 1 , wherein said pH-independent polymer is selected from a group consisting of hydroxypropyl cellulose, hypromellose (hydroxypropyl methyl cellulose), methyl cellulose, polyethylene oxide, acacia, carbomer homopolymer type A NF; carbomer homopolymer type B NF, hydroxyethyl cellulose, carrageenan, tragacanth, xanthan gum, povidone, alginic acid and salts thereof, polyvinyl alcohol, carboxymethylcellulose; ethylcellulose, cellulose acetate, cellulose acetate butyrate, poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer, poly(ethyl acrylate-co-methyl methacrylate-cotrimethylammonioethyl methacrylate chloride), polyvinyl acetate, and cellulose acetate propionate.
19 . The formulation of claim 1 further comprising 2-(2-Aminoethyl)-3-(4-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one.
20 . An immediate release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation.
21 . The formulation of claim 1 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions.
22 . A method of treating ADHD comprising administering to a subject in need thereof an effective amount of a dosage form of claim 21 .
23 . The formulation of claim 20 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions.