LOW-FRIABILITY, PATIENT-FRIENDLY ORALLY DISINTEGRATING FORMULATIONS

Abstract

The present invention relates to a rapidly disintegrating orally administratable solid dosage formulation that includes at least one active ingredient, at least one first disintegration agent that is at least one type-C methacrylic acid copolymer according to the U.S. Pharmacopoeia National Formulary US/NF, a second disintegration agent of crospovidone or a cross-linked povidone polymer derivative thereof, and a non-cariogenic diluent that does not increase glucose blood levels. The at least one first disintegration agent does not function as an enteric coating, insulation coating intended to protect active ingredient(s), or coating intended to mask taste or smell. The solid dosage form has a mass of about 50 to about 1000 mg, and the at least one first disintegration agent is present in the dosage form in an amount not exceeding 15%, with respect to the total weight of the dosage form. The second disintegration agent is present in the dosage form in an amount not exceeding 15% with respect to the total weight of the dosage form. The first and the second disintegration agent are present in total amounts that provide a weight ratio of about 1:1 to about 1:3, wherein the dosage form provides at least one of the in vitro or in vivo disintegration time that is less than 30 seconds, and has a friability of 1% or less according to the U.S. Pharmacopoeia test.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be further described in the following description with references to the drawings in which:

FIG. 1 is a graphic illustration of the effect of compression force on the disintegration time of disintegrating formulations including various diluents;

FIG. 2 is a graphic illustration of the dissolution profiles of a formulation prepared according to the present invention over a storage period of three months; and

FIGS. 3-4 are graphic illustrations of the effect of press rotation speed on friability, hardness, and in vitro disintegration time of formulations prepared according to the present invention.

Claims

1. A rapidly disintegrating orally administratable solid formulation comprising a matrix that includes: at least one first pH-dependent water-soluble disintegration agent that is at least one Type C methacrylic acid copolymer according to the U.S. Pharmacopoeia National Formulary US/NF;at least one second water-insoluble disintegration agent which is non-swelling in water; anda non-cariogenic diluent that does not increase glucose blood levels,wherein the solid dosage form has a mass of about 50 to about 1000 mg, the at least one first disintegration agent is present in the dosage form in an amount not exceeding 15%, with respect to the total weight of the dosage form, the at least second disintegration agent is present in the dosage form in an amount not exceeding 15% with respect to the total weight of the dosage form, and the at least first and second disintegration agents are present in total amounts that provide a weight ratio of about 1:1 to about 1:3, wherein the dosage form provides at least one of an in vitro or in vivo disintegration time that is less than 30 seconds, and has a friability of 1% or less according to the U.S. Pharmacopoeia test.

2. The formulation of claim 1 which further comprises at least one active ingredient.

3. The formulation of claim 1, wherein the non-cariogenic diluent consists substantially of mannitol and is present in an amount of between 25% and 85% by weight of the formulation.

4. The formulation of claim 1, wherein the formulation is substantially free of lactose or fructose responsible for intestinal discomfort in populations suffering from sugar intolerance or which is substantially free of precursors being metabolized in the human body into lactose or fructose.

5. The formulation of claim 1, which further comprises one or more diluents or fillers, sweeteners, binders, flavors and flavor enhancers, buffers, preservatives, antioxidants, lubricants, bioadhesive agents, colorants, flow agents, plasticizers, film forming agents, coating agents, polishing agents, shining agents, or mixtures thereof.

6. The formulation of claim 5, wherein the sweetener is not contraindicated in populations suffering from phenylketonury.

7. The formulation of claim 1, wherein the type-C methacrylic acid copolymer is a compound having the formula:

8. The formulation of claim 1, wherein the amount of water-insoluble, non-swelling inactive ingredients in the formulation does not exceed 20% by weight of the total formulation.

9. The formulation of claim 1, wherein the at least one active ingredient is used to treat cardiovascular disorders, respiratory disorders, gastrointestinal disorders, renal disorders, neurologic disorders, psychiatric disorders, endocrinologic disorders, gynecologic and obstetric disorders, urologic disorders, immunologic disorders, bone and joint disorders, disorders of the eyes, ears, nose and throat, dermatologic disorders, hematologic disorders, infectious diseases, oncologic disorders, nutritional disorders.

10. The formulation of claim 1, wherein the at least one active ingredient is selected from the class of hypnotics, analeptics, analgesics, local or general anaesthetics, muscle relaxants, antiepileptics, antiParkinsonian drugs, antiemetics, hormones, anti-hormones, lipid-lowering agents, phosphodiesterase inhibitors, antiarrhythmics, beta-receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, antimigraine agents, antiasthmatic drugs, antitussives drugs, antiacids, modulators of the gastrointestinal motility, antiulcer drugs, laxatives, antidiarrhea drugs, ulcerative colitis and Crohn's disease drugs, choleretic and cholekinetic drugs, diuretics, vitamins, anti-infectives drugs, mitotic inhibitors, cytostatics, narcotics, analgesics, anesthetics.

11. The formulation of claim 1, wherein the at least one active ingredient is selected for the group consisting of meloxicam, androgens, estrogens, progestins, clonazepam, zolpidem, buprenorphine, naloxone, atorvastatin, candesartan, glimepiride, rosiglitazone, domperidone, cetirizine, sildenafil, amlodipine, zafirlukast and combination thereof.

12. The formulation of claim 1, wherein the solid dosage form has a mass of 50 to 150 mg, with the active ingredient being present in the dosage form in an amount not exceeding 15 mg, the at least one first disintegration agent being present in the dosage form in an amount not exceeding 10%, with respect to the total weight of the dosage form, the second disintegration agent being present in the dosage form in an amount not exceeding 10% with respect to the total weight of the dosage form, and with the first and second disintegration agents being present in total amounts that provide a weight ratio of about 1:1 to about 1:2, wherein the dosage form provides at least one of the in vitro or in vivo disintegration time that is less than 10 seconds, and has a friability of 0.8% or less according to the U.S. Pharmacopoeia test when manufactured on rotary tableting machine operated at industrial speeds up to 60 rpm, and being obtained by direct compression.

13. The formulation of claim 1, wherein the solid dosage form has a mass of 150 to 300 mg, with the active ingredient being present in the dosage form in an amount not exceeding 50 mg, the at least one first disintegration agent being present in the dosage form in an amount not exceeding 15%, with respect to the total weight of the dosage form, the second disintegration agent being present in the dosage form in an amount not exceeding 15% with respect to the total weight of the dosage form, and with the first and second disintegration agents being present in total amounts that provide a weight ratio of about 1:1 to about 1:3, wherein the dosage form provides at least one of the in vitro or in vivo disintegration time that is less than 15 seconds, and has a friability of 0.8% or less according to the U.S. Pharmacopoeia test when manufactured on rotary tableting machine operated at industrial speeds up to 60 rpm, and being obtained by direct compression.

14. The formulation of claim 1, wherein the solid dosage form has a mass of 300 to 500 mg, with the active ingredient being present in the dosage form in an amount not exceeding 200 mg, the at least one first disintegration agent being present in the dosage form in an amount not exceeding 15%, with respect to the total weight of the dosage form, the second disintegration agent being present in the dosage form in an amount not exceeding 15% with respect to the total weight of the dosage form, and with the first and second disintegration agents being present in total amounts that provide a weight ratio of about 1:1 to about 1:3, wherein the dosage form provides at least one of the in vitro or in vivo disintegration time that is less than 20 seconds, and has a friability of 1% or less according to the U.S. Pharmacopeia test when manufactured on rotary tableting machine operated at industrial speeds up to 60 rpm, and being obtained by direct compression.

15. The formulation of claim 1, wherein the solid dosage form has a mass of 500 to about 1000 mg, with the active ingredient being present in the dosage form in an amount not exceeding 500 mg, the at least one first disintegration agent being present in the dosage form in an amount not exceeding 15%, with respect to the total weight of the dosage form, the second disintegration agent being present in the dosage form in an amount not exceeding 15% with respect to the total weight of the dosage form, and with the first and second disintegration agents being present in total amounts that provide a weight ratio of about 1:1 to about 1:3, wherein the dosage form provides at least one of the in vitro or in vivo disintegration time that is less than 30 seconds, and has a friability of 1% or less according to the U.S. Pharmacopoeia test when manufactured on rotary tableting machine operated at industrial speeds up to 60 rpm, and being obtained by direct compression.

16. A process for preparing the solid dosage formulation of claim 1, which comprises directly compressing the components to form the formulation.

17. A method of administering an active ingredient which comprises orally administering the formulation of claim 1 to a patient in need thereof so that the solid formulation rapidly disintegrates to administer the active ingredient.