QUICK DISSOLVE COMPOSITIONS AND TABLETS BASED THEREON
The invention provides a composition useful for making oral dosage forms capable of dissolving in the mouth in less than 40 seconds without the need for a conventional super disintegrant and having a friability of less than 1%; wherein the composition includes liquiflash particles and an excipient mass. A preferred excipient mass according to the invention contains a directly compressible inorganic salt; a cellulose derivative or a combination of a directly compressible inorganic salt and a cellulose derivative. Preferably, the liquiflash particles and the excipient mass are combined in proportions such that the active ingredient remains substantially within the microspheres when the composition is compressed to obtain a dosage form having a hardness of 20 to 50 N. The compositions of the invention allow for the fabrication of oral dosages having improved hardness and friability.
1 . A direct compression quick dissolve oral dosage form comprising:
(a) a drug-containing microparticle, and
(b) an excipient mass comprising:
(i) at least one of a directly compressible inorganic salt, a cellulose derivative, and a mixture thereof and
(ii) at least one directly compressible filler;
wherein said oral dosage form is a fast dissolving oral dosage form that dissolves in the mouth in less than about 40 seconds, has a friability of less than about 1%, and is manufactured by direct compression processing.
2 . The oral dosage form of claim 1 , wherein the drug-containing microparticle comprises at least one drug, and a combination of at least one solubilizer and at least one spheronization aid.
3 . The oral dosage form of claim 1 , wherein the excipient mass is comprised of about 50% directly compressible inorganic salt and about 50% cellulose derivative.
4 . The oral dosage form of claim 1 , wherein the excipient mass comprises at least one directly compressible inorganic salt selected from the group consisting of directly compressible dibasic calcium phosphate dihydrate, magnesium aluminum silicate NF, and mixtures thereof.
5 . The oral dosage form of claim 1 , wherein the excipient mass comprises a linear polyol.
6 . The oral dosage form of claim 1 , wherein the excipient mass comprises a directly compressible polyol.
7 . The oral dosage form of claim 1 , wherein the excipient mass further comprises mannitol; xylitol or a mixture thereof.
8 . The oral dosage form of claim 1 , wherein the excipient mass further comprises lactose, maltose, sucrose or a mixture thereof.
9 . The oral dosage form of claim 1 , wherein the drug-containing microparticles are liquiflash particles, and the drug-containing microparticles and the excipient mass are combined in proportions selected such that the drug remains within the liquiflash particles when the composition is compressed to obtain a dosage form having a hardness of from about 20 N to about 50 N.
10 . The oral dosage form of claim 1 , wherein the drug-containing microparticles particles are coated.
11 . The oral dosage form of claim 1 , wherein the drug-containing microparticles particles are coated with at least one taste-masking coating.
12 . The oral dosage form of claim 10 , wherein the coating contains at least one cellulosic polymer.
13 . The oral dosage form of claim 10 , wherein the coating comprises a polymethacrylate polymer.
14 . The oral dosage form of claim 1 , which dissolves in the mouth in less than about 30 seconds.
15 . The oral dosage form of claim 1 , wherein the excipient mass comprises a super disintegrant.
16 . The oral dosage form of claim 1 , wherein the excipient mass comprises from 0% to about 3% by weight of a super disintegrant.
17 . The oral dosage form of claim 1 , wherein said oral dosage form dissolves in the mouth in less than about 30 seconds and comprises from about 5% to about 45% by weight of drug-containing microparticles, and from about 25% to about 85% by weight of an excipient mass, wherein the excipient mass contains less than about 2.5% by weight of a super disintegrant.
18 . The oral dosage form of claim 1 , comprising from about 5% to about 20% by weight of microcrystalline cellulose.
19 . The oral dosage form of claim 1 , wherein the drug-containing microparticles comprise a drug selected from the group consisting of fluoxetine; paroxetine; zolpidem; tevenen; Cox-2 inhibitor; Ace inhibitor; a calcium channel blocker, and mixtures thereof.
20 . The oral dosage form of claim 1 , wherein the drug-containing microparticles comprise a drug selected from the group consisting of antitussives, antihistamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, antacids, ion exchange resins, anti-cholesterolemics, anti-lipid agents, antiarrhythmics, antipyretics, analgesics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, anti-infectives, psycho-tropics, antimanics, stimulants, gastrointestinal agents, sedatives, antidiarrheal preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, antitumor drugs, anticoagulants, antithrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypoglycemic agents, thyroid and antithyroid preparations, diuretics, antispasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic drugs, erythropoietic drugs, antiasthmatics, cough suppressants, mucolytics, H 2 -antagonists, anti-uricemic drugs and mixtures thereof.
21 . The oral dosage form of claim 1 , wherein the drug-containing microparticles comprise glyceryl stearate.
22 . The oral dosage form of claim 1 , wherein the drug-containing microparticle comprises hydroxypropylmethylcellulose.
23 . The oral dosage form of claim 1 , wherein the excipient mass comprises low substituted hydroxypropyl cellulose.
24 . The oral dosage form of claim 1 , wherein the excipient mass comprises microcrystalline cellulose.
25 . The oral dosage form of claim 1 , wherein the excipient mass comprises crospovidone.
26 . The oral dosage form of claim 1 , wherein the excipient mass comprises microcrystalline cellulose, crospovidone, and low substituted hydroxypropyl cellulose.
27 . The oral dosage form of claim 1 , wherein the excipient mass comprises mannitol.
28 . The oral dosage form of claim 1 , wherein the excipient mass comprises a sweetener.
29 . The oral dosage form of claim 1 , wherein the directly compressible filler comprises a directly compressible polyol.
30 . The oral dosage form of claim 29 , wherein the directly compressible polyol comprises at least one of mannitol, sorbitol, xylitol, or a mixture thereof.
31 . The oral dosage form of claim 1 , wherein the directly compressible filler comprises at least one of lactose, maltose, sucrose, dextrose, or a mixture thereof.