Solid form

• US 20080014228A1
• Filed: 05/16/2007
• Published: 01/17/2008
• Est. Priority Date: 07/14/2006
• Status: Abandoned Application

• Current Assignee: FMC Corporation
• Original Assignee: FMC Corporation
• Inventors: MacLeod, Graeme, Cengic, Dzenana, Darmuzey, Olivia, Stokes, Kevin M.
• Application Number:
  US11/803,795
• Publication Number:
  US 20080014228A1
• Time in Patent Office: Days
• US Class Current: 424/401
• CPC Class Codes: A61J 3/07 into the form of capsules or similar small containers for oral use
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An enrobed solid form comprising a film enrobing a compacted fill material having at least one active material, the solid form shows a weight loss that is less than 1% during a 30 minutes USP Friability Test, the fill material having a density of at least 0.5 g/ml based on the total solid volume of the solid form and a tensile strength less than 0.9 MPa, and the at least one active material within the solid form has an immediate release profile. The solid form is useful in effective delivery of high dose levels of active material.

Claims

1. A solid form comprising at least one film enrobing a compacted fill material wherein:

i) said compacted fill material comprises at least one active material and at least one of a disintegrant and a wetting agent;

ii) said solid form has a weight loss that is less than 1% during a 30 minute USP Friability Test USP 29 Test Number 1216; and

iii) said compacted fill material in said solid form has a density of at least 0.5 g/ml based on the total solid volume of the solid form and a tensile strength of less than 0.9 MPa; and

iv) the at least one active material within the solid form exhibits immediate release.

3. A solid form according to claim 1 or claim 2 wherein the active material in said solid form comprises at least one pharmaceutical active and said at least one pharmaceutical active has a mean dissolution which meets the USP dissolution specifications in the test specified in the USP Edition 29 Test Number 711 at page 2673 for said active material when said active material is placed in a dissolution medium as specified in the USP dissolution specification or selected from dissolution media specified in the USP according to the solubility properties of said active material.

4. A solid form according to claim 1 or claim 2 wherein said compacted fill material comprises a moderate to high amount of said at least one active material.

5. A solid form according to claim 4 wherein said compacted fill material comprises a high amount of said at least one active material.

6. A solid form according to claim 1 or claim 2 wherein the disintegrant comprises at least one super disintegrant and said fill material has a density of 0.5 to 1.1 g/ml, said at least one active material has a solubility of 1 g of active material in ≧

10 g of water, and wherein at least one of said active materials has a mean dissolution of at least 75% in 300 seconds when the active material is tested in the test specified in the USP Edition 29 Test Number 711 at page 2673 for said active material in a dissolution medium as specified in the USP dissolution specification or, if the medium is not specified in the said specification, the dissolution medium is selected according to the solubility properties of the active material from dissolution media specified in the USP or from;

(i) water, (ii) 0.1 M HCI or (iii) phosphate buffer having a pH between 5.8 and 8.0.

7. A solid form according to claim 6, wherein said super disintegrant comprises at least one of croscarmellose sodium, sodium starch glycolate, crosslinked polyvinyl pyrrolidone or low substituted hydroxypropyl cellulose.

8. A solid form according to claim 6 wherein said at least one active material has a mean dissolution of at least 85% in 300 seconds in any of said dissolution media.

9. A solid form according to claim 6 wherein said at least one active material has a mean dissolution of at least 95% in 300 seconds in any of said dissolution media.

10. A solid form according to claim 6, wherein said at least one active material has a solubility in water of 1 g active in 10 to 30 g water.

11. A solid form according to claim 6, wherein said at least one active material has a solubility in water selected from the range of 1 g active in 30 to 100 g water.

12. A solid form according to claim 6 wherein said at least one active material has a solubility in water of 1 g active in 100 to 1,000 g water.

13. A solid form according to claim 6, wherein said at least one active material has a solubility of 1 g active in 1,000 to 10,000 g water.

14. A solid form according to claim 6, wherein said at least one active material has a solubility in water of 1 g active in more than 10,000 g water.

15. A solid form according to claim 6 wherein said super disintegrant is present in an amount of 0.1 to 10% by weight of the compacted fill material.

16. A solid form according to claim 1 or claim 2 wherein the compacted fill material in said solid form has a density from 0.55 to 1.04 g/ml.

17. A solid form according claim 1 or claim 2 wherein the compacted fill material has a density from 0.75 to 1 g/ml.

18. A solid form according claim 1 or claim 2 wherein the solid form has a tensile strength of at least 1.3 MPa.

19. A solid form according claim 1 or claim 2 wherein said at least one active material is present in an amount of at least 30% by weight of the compacted fill material.

20. A solid form according to claim 1 or claim 2 further comprising a filler.

21. A solid form according to claim 20, wherein said filler comprises at least one of microcrystalline cellulose, dicalcium phosphate, lactose calcium carbonate, calcium phosphate dibasic anhydrous, calcium phosphate dibasic dehydrate, calcium phosphate tribasic, powdered cellulose, silicified microcrystalline cellulose, cellulose acetate, compressible sugar, confectioners sugar, dextrin, dextrose, ethylcellulose, fructose, lactitol, starch, pregelatinized starch, sucrose, talc, xylitol, maltodextrin, magnesium carbonate, maltose, mannitol, polydextrose, sodium alginate, sodium chloride, sorbitol, sucrose, sugar spheres, acacia, carrageenan, carbomer, chitosan, hydroxypropylmethylcellulose, carboxymethylcellulose sodium, gelatin, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, povidone, zein, citric acid, sodium bicarbonate, alginic acid, carboxymethylcellulose calcium, colloidal silicon dioxide, low substituted hydroxypropyl cellulose.

22. A solid form according to claim 20, wherein said filler is present in an amount less than 70% by weight of the compacted fill material.

23. A solid form according to claim 22, wherein said filler is present in an amount of 1 to 10% by weight of the compacted fill material.

24. A solid form according to claim 1 or claim 2, wherein said solid form does not contain a filler.

25. A solid form according to claim 1 or claim 2, wherein said active material comprises at least one of an analgesic, antiangina, antianaemia, antibiotic, antiarrhythmic, antidiarrheal, antidiuretic, antidepressant, antiemetic, antifungal, antirheumatic, antiviral, antiprotozoal, antihistamine, antihypertensive, anti-inflammatory, antimigraine, antinausea, antispasmodic, anxiolytic, beta blocker, calcium channel blocker, sedative, hypnotic, antipsychotic, bronchodilator, decongestant, cough expectorant, cough suppressant, antiasthma drug, corticosteroid, actives for treatment of cough or common cold, muscle relaxant, erectile dysfunction active or motion sickness active.

26. A solid form according to claim 1 or claim 2, comprising at least two active materials wherein the active materials are selected from:

i) an antibiotic in combination with a decongestant, an anti-inflammatory, a cough expectorant, a cough suppressant or an active for treatment of cough or common cold, a proton pump inhibitor;

ii) an anti-HIV, anti-malaria active material, an anti-hypertension and anti-cholesterol,

iii) two or more active materials from the same class of active materials, the class being selected from respiratory actives, gastronintestinal actives, cardiovascular actives, antidiabetes actives, central nervous system actives, anti-infection actives, anti-viral actives, analgesics, anti-inflammatory actives, antibiotics, cough suppressants, expectorants, mucolytics, and nasal decongestants.

27. A solid form according to claim 1 or claim 2, wherein the said at least one active material comprises at least one of paracetamol, pseudoephedrine, acravastine, lamivudine, abacavir, pravastatin, Roziglitazone, ezetimibe, Clavulanate, sulfamethoxazole, benazepril, Valsartan, Irbesartan, Losartan, Dutasteride, tamsolusin, Atazanavir, ritonavir, propoxyphene, Hydrocodone, Metocarbamol, Memantine, Donepezil, Glyburide, Pioglytazone, Glimepiride, Benazepril, Torcetrapib, Eprosartan, Telmisartan, Olmesartan, Lopinavir, Emtricitabine, Tenofovir, Amprenavir, Tipranavir, Atovaquone, Proguanil, 5-aminosalicylic acid, 4-aminophthalic acid, Bismuth citrate, Bismuth subsalicylate, Montelukast, pseudoephedrine, Guaifenesin, ibuprofen, nifedipine, betamethasone acetate, methylprednisolone, dextromethorphan, cinnarazine, simvastatin, ciprofloxacin, glipizide, risperidone, glibenclamide, fenofibrate, isosorbide mononitrate, isosorbide dinitrate, acetazolamide, levothyroxine sodium, omeprazole, aspirin, codeine, dihydroergotamine, diazepam, theophylline, sildenafil citrate, vardenafil hydrochloride, amlodipine besylate, zolpidem tartrate, acetaminophen, methocarbamol, ramipril, digoxin, enalapril maleate, fluoxetine hydrochloride, fexofenadine hydrochloride, olanzapine, methyldopa, hydrochlorothiazide, timolol maleate, alendronate sodium, thiabendazole, rofexocib, dicoflenac, bepridil hydrochloride, atorvastatin hydrochloride, sertraline hydrochloride, famciclovir monohydrate, nabumetone, cimetidine, ketoprofen, etodolac, amiodarone hydrochloride, indomethacin, cefaclor, diltiazem, verapamil, felodipine, isradipine, nicardipine, prazosin, disopyramide, pentoxifilline, venlafaxine, alfuzosin, doxazosin, famotidine, ranitidine, pirenzipine, lansoprazole, loperamide, sulfasalazine, prednisolone, furosemide, amiloride, triamterene, verapamil, atenolol, propranolol, captopril, glyceryl trinitrate, caffeine, aminophylline, cetirizine, loratadine, chlorpheniramine maleate, diphenhydramine, dothiepin, amitriptyline, pheneizine, paroxetine, fenfluramine, dimenhydrinate, ondansetron, domperidone, metoclopramide, tramadol, dihydrocodeine, pethidine, sumatriptan, amoxicillin, ampicillin, cefuroxime, cephalexin, tetracycline, erythromycin, co-trimoxazole, sulphadiazine, trimethoprim, nitrofurantoin, fluconazole, ketoconazole, acyclovir, zidovudine, chloroquine, mefloquin, metronidazole, metformin, chlorpropamide, ferrous sulphate, azapropazone, fenbufen, flurbiprofen, ketoprofen, naproxen, piroxicam, mefanamic acid, celecoxib, licofelone, tadalafil, mycophenolate, valgancyclovir, valacyclovir, sevelamer, metaxolone, nelfinavir, duranavir, tipranavir, levetiracetam, capecitabine, moxifloxacin, morphine, levofloxacin, clarithromycin, pregabalin, esomeprazole, quetiapine, efavirenz, oxcarbazepine, colesevelam, zileuton, nitazoxanide, clofibrate, praziquantel, sucralfate, cefprozil, indinavir, ganciclovir, oxaprozin, divalproex, cefadroxil, felbamate, potassium chloride, saquinavir, fosamprenavir, hydroxyurea, gabapentin, niacin, omega-3 acid ethyl esters, calcium acetate, progesterone, procainamide, delavirdine, ribavirin, propafenone, eprosartan, tocainide, tinidazole, choline magnesium trisalicylate, azithromycin, linezolid, lorazepam, oxazepam, lormetazepam, flunitrazepam, haloperidol, triptorelin, leuprorelin, lanreotide acetate, octreotide acetate, methylxanthin, tamsulosin, codeine hydrochloride, dextromoramide tartrate, ethymorphine hydrochloride, magnesium salicylate, methadone hydrochloride, oxycodone hydrochloride, sufentanil citrate, ephedrine, tramazoline hydrochloride, brompheniramine maleate, emedastine fumarate, and pharmaceuticaly or nutraceuticaly acceptable salts, acids, esters, isomers, and metabolites thereof.

28. A solid form according to claim 1 or claim 2, comprising at least two active materials wherein the active materials are selected from:

paracetamol and caffeine;

aspirin and paracetamol;

paracetamol and pseudoephedrine;

paracetamol and phenylephrine;

ibuprofen and codeine;

ibuprofen and pseudoephedrine;

paracetamol and diphenhydramine;

acravistine and pseudoephedrine;

paracetamol and dextromethorphan;

paracetamol and guaphenesin;

paracetamol, caffeine, aspirin;

aspirin and caffeine;

zidovudine, iamivudine and abacavir;

pravastatin and aspirin;

lamivudine and zidovudine;

roziglitazone and metformin;

ezetimibe and fenofibrate;

amoxicillin and clavulanate;

trimetoprim and sulfamethoxazole;

amlodipine and benazepril;

valsartan and hydrochlorothiazide;

irbesartan and hydrochlorothiazide;

losartan and hydrochlorothiazide;

fenofibrate and metformin;

abacavir and lamivudine;

dutasteride and tamsolusin;

atazanavir and ritonavir;

ritonavir and saquinavir;

propoxyphene and paracetamol;

hydrocodone and paracetamol;

tramadol and paracetamol;

metocarbamol and paracetamol;

memantine and donepezil;

glyburide and metformin;

pioglytazone and metformin;

rosiglitazone and glimepiride, benazepril and hydrochlorothiazide;

atorvastatin and torcetrapib;

eprosartan and hydrochlorothiazide;

amlodipine and atorvastatin;

ezetimibe and simvastatin;

telmisartan and hydrochlorothiazide;

olmesartan and hydrochlorothiazide;

lopinavir and ritonavir;

emtricitabine and tenofovir;

fosamprenavir and ritonavir;

amprenavir and ritonavir;

tipranavir and ritonavir;

atovaquone and proguanil;

lansoprazole, amoxicillin and clarithromycin;

lansoprazole and naproxen;

5-aminosalicylic acid and 4-aminophthalic acid acid;

clarithromycin, ranitidine and bismuth citrate;

bismuth subsalicylate, metronidazole and tetracycline;

montelukast and loratadine;

fexofenadine and pseudoephedrine;

Guaifenesin and pseudoephedrine.

29. A solid form according to claim 1 or claim 2 comprising a wetting agent selected from at least one of hypromellose, docusate sodium, sodium lauryl sulfate, polyoxyethylene sorbitan fatty acid esters, sorbitan esters, polyoxyethylene alkyl ethers, dioctyl calcium sulfosuccinate, povidone, cyclodextrins, poloxamers, glyceryl monostearate,

30. A solid form according to claim 1 or claim 2 comprising a wetting agent which is present in an amount of 0.01 to 10.0 wt % based on the total weight of the compacted fill material.

31. A solid form according to claim 1 or claim 2 in which the compacted fill material comprises a wetting agent and either a disintegrant or a super-disintegrant.

32. A solid form according to claim 1 or claim 2 wherein the compacted fill material has a tensile strength less than 0.2 MPa.

33. A solid form according to claim 1 or claim 2, wherein said disintegrant is present in an amount of 0.1 to 25% by weight of the compacted fill material.

34. A solid form according to claim 1 or claim 2 wherein said at least one active material has a solubility in water of 1 g active in 1-10 g water.

35. A solid form according to claim 1 or claim 2 wherein said at least one active material has a solubility in water of 1 g active in less than 1 g water.

36. A solid form according to claim 1 or claim 2, wherein said active material is a powder material comprising at least one of granules, micronized powders, spray-dried powders and freeze-dried powders and pellets.

37. A solid form according to claim 1 or claim 2, wherein said disintegrant comprises at least one of croscarmellose sodium, sodium starch glycolate, crosslinked polyvinyl pyrrolidone or low substituted hydroxypropyl cellulose, alginic acid, calcium phosphate, carboxymethylcelluloses, powdered cellulose, chitosan, colloidal silicon dioxide, guar gum, magnesium aluminium silicate, methylcellulose, microcrystalline cellulose, povidone, sodium alginate, starch, pregelatinised starch.

38. A solid form according to any claim 1 or claim 2, wherein the film enrobing the compacted fill material is a water-soluble film.

39. A solid form according to claim 1 or claim 2 for use in a method of treatment of the human or animal body by therapy.

40. A method of treatment of the human or animal body comprising administering a solid form according to claim 1 or claim 2 to the human or animal body.

2. A solid form comprising at least one film enrobing a compacted fill material wherein the compacted fill material comprises at least one active material and at least one of a disintegrant and a wetting agent and the compacted fill material is selected from a pharmaceutical product, food product, a veterinary product, a cosmetic, an appetite suppressant, a detergent product and a nutraceutical product, the said solid form shows a weight loss that is less than 1% during a 30 minutes United States Pharmacopeia Friability Test USP 29 Test Number 1216 (page 3046) and the said solid form dissolves with an immediate release profile.