FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATON
(See Section 10 and Rule 13)
Title of Invention:
MODIFIED RELEASE PHARMACEUTICAL PREPARATIONS
APPLICANT(S):
RUBICON RESEARCH PRIVATE LIMITED
A company incorporated in India,
having place of business at:
221, Annexe Building Goregaon Mulund Link Road,
Opposite Indira Container Yard, Off L.B.S. Marg,
Bhandup (West) Mumbai 400078,
Maharashtra, India.
The following specification particularly describes the invention and the manner in which it is to be performed.
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CLAIMS
We claim:
1. A modified release composition comprising multitude of modified release beads comprising a matrix of drug-ion exchange resin complex and at least one non-polymeric multifunctional excipient; substantially coated with at least one outer release rate modifying layer; wherein the non-polymeric multifunctional excipient is a fatty acid ester, wax, fatty acid, fatty alcohol, hydrogenated vegetable oil or any combination thereof and the drug-ion exchange resin complex comprises at least one active agent and at least one ion exchange resin.
2. The composition of claim 1 wherein the active agent is psychostimulant, antihistamine, expectorant or mucolytic, anti-tussive agent, serotonin and norepinephrine reuptake inhibitor, sympatholytic, antimuscarinic and urinary antispasmodic, PDE-5 inhibitor, anti-Alzheimer’s agent, analgesic, decongestant, analeptic agent; anesthetic agent; anti-asthmatic, anti-arthritic agent; anti-cancer agent; anti-cholinergic agent; anti-convulsant agent, anti-depressant agent; antidiabetic; anti-helminthic agent; anti-diarrheal agent; anti-epileptic, anti-hyperlipidemic agent; antihypertensive, antihypotensive, peripheral vasodilators or vasoconstrictors, respiratory agents, anti-infective agent; anti-inflammatory agent; non-steroidal anti-inflammatory agent, anti-emetic, anti-migraine agent; anti-neoplastic agent; anti-tubercular agent; antibiotic, antacid; antiulcer agent; anti-Parkinsonism drug; anti-pruritic agent; antipsychotic agent; anti-pyretic agent; anti-spasmodic, anti-viral agent; appetite suppressant; attention deficit hyperactivity disorder treating agent; cardiovascular agent, calcium channel blocker, antianginal agent; central nervous system agent; beta-blocker; antiarrhythmic agent; bronchodilator, central nervous system stimulant; diuretic, genetic material; hormonolytic; hypnotic; hypercalcemic; hypoglycemic agent; immunosuppressive agent; beta-agonist; narcotic antagonist; nicotine; nutritional agent; parasympatholytic; peptide drug; antihemorrhoidal; psychostimulant; psychotropic; mucolytic; sedative; laxative; vitamin; sialagogue, steroid; sympathomimetic; tranquilizer; vasodilator, antianxiety drug, antidepressant, antipyretic analgesic,
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hypnotic, drug for the treatment of respiratory system disorders, coronary dilator, calcium antagonist, chemotherapeutic drug, antiprotozoan drug and mixtures thereof.
3. The composition of claim 1 wherein the active agent is amphetamine, amphetaminil, atomoxetine, dexmethylphenidate, dextroamphetamine, dextromethamphetamine, fencamfamine, fenethylline, lisdexamfetamine, methylphenidate, mesocarb, pemoline, pipradrol, prolintane, dimenhydrinate, diphenhydramine, chlorpheniramine, brompheniramine, dexchlorpheniramine, hydroxyzine, dexbrompheniramine, fexofenadine, terfenadine, cetirizine, levocetirizine, fexofenadine hydrochloride or dl-chlorpheniramine maleate, ambroxol, bromhexine, carbocisteine, domiodol, guaifenesin, codeine, dextromethorphan, hydrocodone, dihydrocodeine phosphate, codeine phosphate, noscapine hydrochloride, phenylpropanolamine hydrochloride, potassium guaiacolsulfonate, cloperastine fendizoate, levocloperastine fendizoate, dextromethorphan hydrobromide, cloperastine hydrochloride, clovoxamine, desvenlafaxine, duloxetine, levomilnacipran, eclanamine, milnacipran, sibutramine, venlafaxine, alaproclate, citalopram, escitalopram, femoxetine, fluoxetine, fluvoxamine, indalpine, ifoxetine litoxetine, omiloxetine, panuramine, paroxetine, pirandamine, seproxetine, sertraline zimelidine, clonidine, guanfacine, methyldopa, iloperidone, ocaperidone, paliperidone, risperidone, lurasidone, perospirone, revospirone, tiospirone, ziprasidone, chlorpromazine hydrochloride, chlorprothexene hydrochloride, darifenacin, emepronium, fesoterodine, flavoxate, imidafenacin, meladrazine, mirabegron, oxybutynin, propiverine, solifenacin, terodiline, tolterodine, trospium chloride, acetildenafil, aildenafil, avanafil, icariin, lodenafil, mirodenafil, nitrosoprodenafil, sildenafil, sulfoaildenafil, tadalafil, udenafil, vardenafil, memantine, neramexane (1, 3, 3, 5, 5-pentamethylcyclohexan-1-amine), donepezil, tacrine, rivastigmine, galantamine, physostigmine, neostigmine, Huperzine A, icopezil (CP-118954, 5,7-dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo-[4,5-f]-1,2-benzisoxazol-6-one maleate), ER-127528 (4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(3-fluorobenzyl) piperidine hydrochloride), zanapezil (TAK-147;
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3-[1-(phenylmethyl)piperidin-4-yl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propane fumarate), metrifonate (T-588; (−)—R-α-[[2-(dimethylamino)ethoxy]methyl]benzo[b] thiophene-5-methanol hydrochloride), FK-960 (N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide-hydrate), TCH-346 (N-methyl-N-2-pyropinyldibenz[b,f] oxepine-10-methanamine), SDZ-220-581 ((S)-α-amino-5-(phosphonomethyl)-[1,1′-biphenyl]-3-propionic acid), tarenflurbil, tramiprosate, clioquinol, aspirin, morphine, dihydromorphine, oxycodone, selegiline, rasagiline, entacapone, tolcapone, alfentanil, allyprodine, alphaprodine, anileridne, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, cyclazocine, desmorphine, dextromoramide, dexocine, diampromide, dimexoxadol, dimepheptanol, dimethylthiambutene, dioxaphetly butyrate, dipipanone, eptazocine, ethotheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, hydromorphone, hydroxpethidine, isomethadone, ketobermidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol metazocine, methadone, metopon, morphine sulfate, myrophine, nalbuphine, narceine, cicomorphine, norlevorphanol, nomethadonel nalorphine, normophine, norpipanone, ixmymorphone, papavretum, pentazocine, phenadoxone, phenmorphan, phenazocine, phenoperidine, iminodine, piritamide, propheptazine, promedol, properidine, propiram, proposyphene, sufenanil, tramadol, tiline, phenylephrine, pseudoephedrine, theophylline, phenobarbital sodium, phenytoin sodium, valproate sodium barbiturates, amylobarbitone sodium, butabarbital sodium, secobarbital sodium, phenytoin, meprobamate, nitrezepam, captopril, propranolol, hydralazine hydrochloride, propranolol hydrochloride, clonidine hydrochloride, tolazoline hydrochloride, predinisolone, prednisolone sodium phosphate, albuterol, albuterol sulfate, terbutaline, naproxen, diclofenac, indomethacin, ibuprofen, sulindac, meclofenamate sodium, tolmetin sodium, metoclopramide, oleandomycin phosphate, tetracycline hydrochloride, fradiomycin, sulfate, amoxicillin, dicloxacillin sodium, pivmecillinam hydrochloride, carbenicillin indanyl sodium, atropine, scopolamine, scopolamine hydrobromide, metixene hydrochloride, dicyclomine hydrochloride, dl-methylephedrine hydrochloride, dl-methylephedrine
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saccharinate; ethacrynic acid, bendrofluazide, nifedipine, papaverine, diltiazem, nicardipine, chlordiazepoxide hydrochloride, diazepam, alprazolam, imipramine hydrochloride, riseridone, sertraline hydrochloride, paroxitene hydrochloride, venlafaxine hydrochloride, sodium salicylate, etafenone hydrochloride, verapamil hydrochloride, sulfisomidine sodium, kanamycin sulfate, amodiaquine hydrochloride, dl-methyl-ephedrine hydrochloride, dehydrocholic acid, diflunisal, fenoprofen, furosemide, gemfibrozil, progencid, sulindac, salicylic acid, acetylsalicylic acid, acetophenazine, amitriptyline, benztropine, biperiden, bromodiphenhydramine, carbinoxamine, chloperastine, chlorcyclizine, chorpheniramine, chlorphenoxamine, chlorpromazine, clemastine, clomiphene, cyclizine, cyclobenzaprine, cyproheptadine, desipramine, dicyclomine, diphemanil, doxepin, doxylamine, ergotamine, fluphenazine, haloperidol, hydroxychloroquine, hyoscyamine, levopropoxyphene, maprotiline, meclizine, mepenzolate, meperidine, mephentermine, mesoridazine, metformin, methylepherdine, methdilazine, methscopolamine, methysergide, metoprolol, nortriptylene, noscapine, nylindrin, oxymorphone, orphenadrine, phendimetrazine, phentermine, phenylpropanolamine, pyrilamine, tripelennamine, triprolidine, promazine, propoxyphene, propanolol, quinidine, aminocaproic acid, aminosalicylic acid, isoxurprine, melphalan, nalidixic acid, paraaminosaliclic acid, chloropheniramine, niacin, methylphenidate hydrochloride, dexmethylphenidate hydrochloride, oxymorphone hydrochloride, hydrocodone bitartrate, albuterol sulfate, albuterol phosphate, chlorpheniramine maleate, metformin hydrochloride, oxybutynin hydrochloride, saligenine hydrochloride, cetrizine hydrochloride, ranitidine hydrochloride or combinations thereof in the form of free base or acid or pharmaceutically acceptable salts, prodrugs, active metabolites, polymorphs, solvates, hydrates, enantiomers, optical isomers, tautomers or racemic mixtures thereof.
4. The composition of claim 1 wherein the ion exchange resin is a cation exchange resin or an anion exchange resin or any combination thereof; said cation exchange resin being a copolymer of methacrylic acid and
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divinylbenzene, a sodium polystyrene sulfonate resin, a sulfonated copolymer of styrene and divinylbenzene, a crosslinked polyacrylic acid resin, a polyacrylate resin, a crosslinked carboxylic acid resin, a crosslinked sulfonic acid resin, a crosslinked phosphonic acid resin, zeolite or any combination thereof.
5. The composition of claim 1 wherein the fatty acid ester is sucrose fatty acid ester, glyceryl fatty acid ester, fatty acid alkyl ester, propylene glycol ester of fatty acid, or any combination thereof.
6. The composition of claim 5 wherein the sucrose fatty acid ester is sucrose stearate, sucrose distearate, sucrose polystearate, sucrose palmitate, sucrose monopalmitate, sucrose dipalmitate, sucrose oleate, sucrose monooleate, sucrose dioleate, sucrose laurate, sucrose monolaurate, sucrose dilaurate, sucrose behenate, sucrose erucate, sucrose caprate, sucrose monocaprate, sucrose dicaprate, sucrose caprylate, sucrose monocaprylate, sucrose dicaprylate, sucrose myristate, sucrose monomyristate, sucrose dimyristate, sucrose linolenate, sucrose monolinolenate, sucrose dilinolenate, sucrose ester of mixed fatty acids, sucrose oligoester, or any mixture thereof.
7. The composition of claim 5 wherein the glyceryl fatty acid esters are mono-, di-and triglycerides, glyceryl behenate; glyceryl monostearate, glyceryl tripalmitate, glyceryl monopalmitate, glyceryl distearate, glyceryl tristearate glyceryl palmitostearate, glyceryl dipalmitate, glyceryl monoleate, glyceryl monolaurate, glyceryl dilaurate, glyceryl trilaurate, glyceryl didocosanoate glycrl tridocosanoate, glyceryl monodocosanoate, glyceryl monocaprote, glyceryl dicaproate, glyceryl tricaproate, glyceryl monomyristate, giyberyl dimyistate, glyceryl trimyristate, glyceryl monodecenoate, glyceryl didecenoate, glycery! tridecenoate; glycowax-932; lauroyl macrogol-32 glycerides; stearoyl macrogol-32 glyceride; fatty acid esters such as those having a fatty acid chain length of about C10 - C.40; glyceryl monoarachidonate, glyceryl monolinoleate, glyceryl monolinolenate, glyceryl monopalmitoleate, glyceryl monocaprylate, glyceryl monococoate,
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glyceryl monocollagenate, glyceryl monoerucate, glyceryl monohydroxystearate, glyceryl monoisopalmitate, glyceryl monolinoleate, glyceryl monolinolenate, glyceryl monomyristate, glyceryl monopentadecanoate, glyceryl monopolyacrylate, glyceryl monotallowate, glyceryl monothiopropionate, glyceryl monocundecylenate or any mixtures thereof.
8. The composition of claim 5 wherein the fatty acid alkyl esters are isopropyl monoarachidonate, isopropyl monolaurate, isopropyl monolinoleate, isopropyl monolinolenate, isopropyl monomyristate, isopropyl monopalmitoleate, isopropyl monooleate, and isopropyl monostearate; methyl monoarachidonate, methyl monolaurate, methyl monolinoleate, methyl monolinolenate, methyl monomyristate, methyl monopalmitoleate, methyl monooleate, methyl monostearate or any mixtures thereof.
9. The composition of claim 5 wherein the propylene glycol esters of fatty acid are propylene glycol monoarachidonate, propylene glycol monolaurate, propylene glycol monolinoleate, propylene glycol monolinolenate, propylene glycol monomyristate, propylene glycol monopalmitoleate, propylene glycol monooleate, propylene glycol monostearate or any combination thereof.
10. The composition of claim 1 wherein the non-polymeric multifunctional excipient is sucrose fatty acid ester or mixtures thereof.
11. The composition of claim 1 wherein the coating comprises at least one release modifier, said release modifier being a water-insoluble release modifier, a water-soluble release modifier or any combination thereof and said water-insoluble release modifier being a polymeric water-insoluble release modifier, a non-polymeric water-insoluble release modifier or any combination thereof.
12. The composition of claim 11 wherein the polymeric water-insoluble release modifier is polyvinyl acetate, polyvinyl chloride, polyvinyl carbonate, ethyl
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cellulose, nitrocellulose, vinylidene chloride-acrylonitrile copolymer,
acrylonitrile-styrene copolymer, ethylene vinyl acetate, cellulose acetate,
cellulose acetate phthalate, cellulose acetate butyrate, copolymer of vinyl
pyrrolidone, hydroxypropylmethylcellulose phthalate, methacrylic acid
copolymer, or methacrylate copolymer or any combination thereof; the nonpolymeric
water insoluble release modifier is a fatty acid, long chain
alcohol, fat, oil, wax, phospholipid, eicosnoid, terpene, steroid, resin or any
combination thereof; and the water-soluble release modifier is
polyvinylpyrrolidone, poloxamer, guar gum, xanthan gum, gum arabic,
tragacanthan, cellulose derivatives such as hydroxypropylmethylcellulose,
hydroxypropyl cellulose, methylcellulose, and hydroxyethyl cellulose,
carboxymethylethyl cellulose, hydroxyethylmethyl carboxymethyl cellulose,
hydroxyethyl methyl cellulose, carboxymethyl cellulose, methylhydroxyethyl
cellulose, or methylhydroxypropyl cellulose or any combination thereof.
13. The composition of claim 1 wherein the formulation is in the form of a
liquid, a solid or a semisolid preparation; said liquid preparation being
suspension and said solid preparation being capsule, tablet, caplet, orally
disintegrating tablet, dispersible tablet, dry suspension for reconstitution,
granule, wafer or bite-dispersion tablet.
14" The composition of claim 1 wherein the modified release composition
further comprises at least one additional active agent delivered in an
immediate release or modified release manner.
15. A modified release suspension comprising multitude of modified release
beads comprising a matrix of drug-ion exchange resin complex and at least
one sucrose fatty acid ester; substantially coated with at least one outer
release rate modifying layer.
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