Pharmaceutical dosage form for mucosal delivery

• US 20030235617A1
• Filed: 02/06/2003
• Published: 12/25/2003
• Est. Priority Date: 02/07/2002
• Status: Abandoned Application

• Current Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Original Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Inventors: Britten, Nancy J., Martino, Alice C., Noack, Robert M., Pierman, Steven A.
• Application Number:
  US10/360,167
• Publication Number:
  US 20030235617A1
• Time in Patent Office: Days
• US Class Current: 424/481
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61P 15/10 for impotence

Abstract

A pharmaceutical tablet is provided comprising an intraorally disintegratable core and an excipient coating adherent thereto, wherein the coating comprises gellan gum. The tablet is suitable for intraoral administration, for example for delivery of a drug contained in the core of the tablet to a subject, at least in part by absorption of the drug via oral mucosa of the subject.

Claims

1. A pharmaceutical tablet comprising an intraorally disintegratable core and an excipient coating adherent thereto, wherein the coating comprises gellan gum.

24. The tablet of claim 1 that is suitable for sublingual administration.

25. The tablet of claim 1 that is suitable for buccal administration.

26. The tablet of claim 1 wherein the coating is present in an amount representing a weight gain of about 0.1% to about 5%.

27. The tablet of claim 1 wherein the gellan gum constitutes about 25% to 100% by weight of the coating.

28. The tablet of claim 1 wherein the gellan gum constitutes about 50% to 100% by weight of the coating.

29. The tablet of claim 1 wherein the coating further comprises at least one additional excipient selected from the group consisting of buffering agents, plasticizers and dispersing and emulsifying agents.

2. A pharmaceutical tablet comprising a drug in a therapeutically and/or prophylactically effective amount, the tablet having an intraorally disintegratable core and a coating adherent thereto, wherein the coating comprises gellan gum, and wherein substantially all of the drug is located in the core and is not commingled with gellan gum.

3. The tablet of claim 2 wherein the drug is selected from the group consisting of ACE inhibitors;

α

-adrenergic agonists;

β

-adrenergic agonists;

α

-adrenergic blockers;

β

-adrenergic blockers;

alcohol deterrents;

aldose reductase inhibitors;

aldosterone antagonists;

amino acids;

anabolics;

analgesics (both narcotic and non-narcotic);

anesthetics;

anorexics;

antacids;

anthelmintics;

antiacne agents;

antiallergics;

antiandrogens;

antianginal agents;

antianxiety agents;

antiarrythmics;

antiasthmatics;

antibacterial agents and antibiotics;

antialopecia and antibaldness agents;

antiamebics;

antibodies;

anticholinergic drugs;

anticoagulants and blood thinners;

anticolitis drugs;

anticonvulsants;

anticystitis drugs;

antidepressants;

antidiabetic agents;

antidiarrheals;

antidiuretics;

antidotes;

antiemetics;

antiestrogens;

antiflatulents;

antifungal agents;

antigens;

antiglaucoma agents;

antihistaminics;

antihyperactives;

antihyperlipoproteinemics;

antihypertensives;

antihyperthyroid agents;

antihypotensives;

antihypothyroid agents;

anti-infectives;

anti-inflammatories (both steroidal and nonsteroidal);

antimalarial agents;

antimigraine agents;

antineoplastics;

antiobesity agents;

antiparkinsonian agents and antidyskinetics;

antipneumonia agents;

antiprotozoal agents;

antipruritics;

antipsoriatics;

antipsychotics;

antipyretics;

antirheumatics;

antisecretory agents;

anti-shock medications;

antispasmodics;

antithrombotics;

antitumor agents;

antitussives;

antiulceratives;

antiviral agents;

anxiolytics;

bactericidins;

bone densifiers;

bronchodilators;

calcium channel blockers;

carbonic anhydrase inhibitors;

cardiotonics and heart stimulants;

chemotherapeutics;

choleretics;

cholinergics;

chronic fatigue syndrome medications;

CNS stimulants;

coagulants;

contraceptives;

cystic fibrosis medications;

decongestants;

diuretics;

dopamine receptor agonists;

dopamine receptor antagonists;

enzymes;

estrogens;

expectorants;

gastric hyperactivity medications;

glucocorticoids;

hemostatics;

HMG CoA reductase inhibitors;

hormones;

hypnotics;

immunomodulators;

immunosuppressants;

laxatives;

medicaments for oral and periodontal diseases;

miotics;

monoamine oxidase inhibitors;

mucolytics;

multiple sclerosis medications;

muscle relaxants;

mydriatics;

narcotic antagonists;

NMDA receptor antagonists;

oligonucleotides;

ophthalmic drugs;

oxytocics;

peptides, polypeptides and proteins;

polysaccharides;

progestogens;

prostaglandins;

protease inhibitors;

respiratory stimulants;

sedatives;

serotonin uptake inhibitors;

sex hormones including androgens;

smoking cessation drugs;

smooth muscle relaxants;

smooth muscle stimulants;

thrombolytics;

tranquilizers;

urinary acidifiers;

urinary incontinence medications;

vasodilators;

vasoprotectants; and

combinations thereof.

4. The tablet of claim 2 wherein the drug is a smoking cessation drug.

5. The tablet of claim 4 wherein the smoking cessation drug is selected from the group consisting of bupropion, ibogaine, nicotine and metabolites thereof.

6. The tablet of claim 2 wherein the drug is an antibacterial drug.

7. The tablet of claim 6 wherein the antibacterial drug is an oxazolidinone.

8. The tablet of claim 7 wherein the oxazolidinone is selected from the group consisting of eperezolid, linezolid, N-[(5S)-3-[3-fluoro-4-[4-(2-fluoroethyl)-3-oxo-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]acetamide, (S)-N-[[3-[5-(3-pyridyl)thiophen-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide, and (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride.

9. The tablet of claim 2 wherein the drug is an antimigraine agent.

10. The tablet of claim 9 wherein the antimigraine agent is a 5-HT receptor agonist.

11. The tablet of claim 10 wherein the 5-HT receptor agonist is selected from the group consisting of almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan.

12. The tablet of claim 2 wherein the drug is useful in treating or preventing an ophthalmic disorder.

13. The tablet of claim 12 wherein the drug is an antiglaucoma or intraocular pressure lowering agent.

14. The tablet of claim 13 wherein the antiglaucoma or intraocular pressure lowering agent is selected from the group consisting of adrenolone, apraclonidine, brimonidine, dipivefrin, acebutolol, adaprolol, alprenolol, atenolol, betaxolol, bufetolol, bufuralol, bunitrolol, bunolol, bupranolol, carteolol, carvedilol, cetamolol, dexpropanolol, labetalol, levobunolol, metipranolol, metoprolol, nadolol, nifenalol, oxyprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, timolol, tolamolol, toliprolol, vaninolol, acetazolamide, dorzolamide, bimatoprost, latanoprost, travoprost, unoprostone isopropyl and combinations thereof.

15. The tablet of claim 2 wherein the drug is an analgesic, antipyretic or anti-inflammatory agent.

16. The tablet of claim 15 wherein the analgesic, antipyretic or anti-inflammatory agent is selected from the group consisting of aceclofenac, acemetacin, e-acetamidocaproic acid, acetaminophen, acetaminosalol, acetanilide, acetylsalicylic acid, S-adenosylmethionine, alclofenac, alclometasone, alfentanil, algestone, allylprodine, alminoprofen, aloxiprin, alphaprodine, aluminum bis(acetylsalicylate), amcinonide, amfenac, aminochlorthenoxazin, 3-amino-4-hydroxybutyric acid, 2-amino-4-picoline, aminopropylon, aminopyrine, amixetrine, ammonium salicylate, ampiroxicam, amtolmetin guacil, anileridine, antipyrine, antrafenine, apazone, beclomethasone, bendazac, benorylate, benoxaprofen, benzpiperylon, benzydamine, benzylmorphine, bermoprofen, betamethasone, bezitramide, α

-bisabolol, bromfenac, p-bromoacetanilide, 5-bromosalicylic acid acetate, bromosaligenin, bucetin, bucloxic acid, bucolome, budesonide, bufexamac, bumadizon, buprenorphine, butacetin, butibufen, butophanol, carbamazepine, carbiphene, carprofen, carsalam, celecoxib, chlorobutanol, chloroprednisone, chlorthenoxazin, choline salicylate, cinchophen, cinmetacin, ciramadol, clidanac, clobetasol, clocortolone, clometacin, clonitazene, clonixin, clopirac, cloprednol, clove, codeine, codeine methyl bromide, codeine phosphate, codeine sulfate, cortisone, cortivazol, cropropamide, crotethamide, deflazacort, desomorphine, desonide, desoximetasone, dexamethasone, dexoxadrol, dextromoramide, dezocine, diampromide, diclofenac, difenamizole, difenpiramide, diflorasone, diflucortolone, diflunisal, difluprednate, dihydrocodeine, dihydrocodeinone enol acetate, dihydromorphine, dihydroxyaluminum acetylsalicylate, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, diprocetyl, dipyrone, ditazol, droxicam, emorfazone, enfenamic acid, enoxolone, epirizole, eptazocine, etersalate, ethenzamide, ethoheptazine, ethoxazene, ethylmethylthiambutene, ethylmorphine, etodolac, etofenamate, etonitazene, etoricoxib, eugenol, felbinac, fenbufen, fenclozic acid, fendosal, fenoprofen, fentanyl, fentiazac, fepradinol, feprazone, floctafenine, fluazacort, flucloronide, flufenamic acid, flumethasone, flunisolide, flunixin, flunoxaprofen, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluoresone, fluorometholone, fluperolone, flupirtine, fluprednidene, fluprednisolone, fluproquazone, flurandrenolide, flurbiprofen, formocortal, fosfosal, gentisic acid, glafenine, glucametacin, glycol salicylate, guaiazulene, halcinonide, halometasone, haloprednone, hydrocodone, hydrocortamate, hydrocortisone, hydromorphone, hydroxypethidine, ibufenac, ibuprofen, ibuproxam, imidazole salicylate, indomethacin, indoprofen, isofezolac, isoladol, isomethadone, isonixin, isoxepac, isoxicam, ketobemidone, ketoprofen, ketorolac, p-lactophenetide, lefetamine, levorphanol, lofentanil, lonazolac, lornoxicam, loxoprofen, lysine acetylsalicylate, mazipredone, meclofenamic acid, medrysone, mefenamic acid, meperidine, meprednisone, meptazinol, mesalamine, metazocine, methadone, methotrimeprazine, methylprednisolone, metiazinic acid, metofoline, metopon, mofebutazone, mofezolac, morazone, morphine, morphine hydrochloride, morphine sulfate, morpholine salicylate, myrophine, nabumetone, nalbuphine, 1-naphthyl salicylate, naproxen, narceine, nefopam, nicomorphine, nifenazone, niflumic acid, nimesulide, 5′

-nitro-2′

-propoxyacetanilide, norlevorphanol, normethadone, normorphine, norpipanone, olsalazine, opium, oxaceprol, oxametacine, oxaprozin, oxycodone, oxymorphone, oxyphenbutazone, papaveretum, paramethasone, paranyline, parecoxib, parsalmide, pentazocine, perisoxal, phenacetin, phenadoxone, phenazocine, phenazopyridine hydrochloride, phenocoll, phenoperidine, phenopyrazone, phenyl acetylsalicylate, phenylbutazone, phenyl salicylate, phenyramidol, piketoprofen, piminodine, pipebuzone, piperylone, piprofen, pirazolac, piritramide, piroxicam, pranoprofen, prednicarbate, prednisolone, prednisone, prednival, prednylidene, proglumetacin, proheptazine, promedol, propacetamol, propiram, propoxyphene, propyphenazone, proquazone, protizinic acid, proxazole, ramifenazone, remifentanil, rimazolium metilsulfate, rofecoxib, salacetamide, salicin, salicylamide, salicylamide o-acetic acid, salicylic acid, salicylsulfuric acid, salsalate, salverine, simetride, sufentanil, sulfasalazine, sulindac, superoxide dismutase, suprofen, suxibuzone, talniflumate, tenidap, tenoxicam, terofenamate, tetrandrine, thiazolinobutazone, tiaprofenic acid, tiaramide, tilidine, tinoridine, tixocortol, tolfenamic acid, tolmetin, tramadol, triamcinolone, tropesin, valdecoxib, viminol, xenbucin, ximoprofen, zaltoprofen and zomepirac.

17. The tablet of claim 15 wherein the analgesic, antipyretic or anti-inflammatory agent is a selective COX-2 inhibitory drug.

18. The tablet of claim 17 wherein the selective COX-2 inhibitory drug is a compound having the formula

19. The tablet of claim 17 wherein the selective COX-2 inhibitor is selected from the group consisting of celecoxib, deracoxib, valdecoxib, parecoxib, rofecoxib, etoricoxib, 2-(3,5-difluorophenyl)-3-[4-(methylsulfonyl)phenyl]-2-cyclopenten-1-one, (S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methyl-1-butyoxy)-5-[4-(methylsulfonyl)phenyl]-3-(2H)-pyridazinone and salts thereof.

20. The tablet of claim 2 wherein the drug is an agent useful in treatment and/or prevention of sexual dysfunction.

21. The tablet of claim 20 wherein the agent is selected from the group consisting of PDE5 inhibitors, cyclic AMP activators, α

-adrenergic antagonists and dopaminergic agonists.

22. The tablet of claim 20 wherein the agent is a compound of formula

23. The tablet of claim 20 wherein the agent is a compound of formula