Solid form

• US 20080286344A1
• Filed: 05/16/2007
• Published: 11/20/2008
• Est. Priority Date: 05/16/2007
• Status: Abandoned Application

• Current Assignee: FMC Corporation
• Original Assignee: FMC Corporation
• Inventors: MacLeod, Graeme, Cengic, Dzenana, Darmuzey, Olivia, Stokes, Kevin M.
• Application Number:
  US11/804,005
• Publication Number:
  US 20080286344A1
• Time in Patent Office: Days
• US Class Current: 424/443
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

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

• • i) the compacted fill material comprises at least one active material;
  • ii) the solid form shows a weight loss that is less than 1% during a 30 minutes USP friability test United States Pharmacopeia (USP) 29 Test Number 1216 (page 3046);
  • iii) the compacted fill material 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 compacted fill material is present in the solid form in at least a first zone and a second zone and the active material is present in at least one of the zones.

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;

ii) said solid form shows a weight loss that is less than 1% during a 30 minutes

USP friability test USP 29 Test Number 1216;

iii) said compacted fill material 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) said compacted fill material comprises at least a first zone and a second zone and said active material is present in at least one of said zones.

3. A solid form according to claim 1 or claim 2 in which the at least one active material has a mean dissolution of at least 75% in 300 seconds in the test specified in the USP Edition 29 Test Number 711 at page 2673 for said active material when the 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 the active material or as selected by the skilled person for example selected from:

(i) the USP for the at least one active material, (ii) water, (iii) 0.1 M HCl or (iv) phosphate buffer having a pH between 5.8 and 8.0.

4. A solid form according to claim 1 or claim 2 wherein the active material is in a form selected from at least one of granules, micronized powders, spray-dried powders, freeze-dried powders or pellets.

5. A solid form according to claim 1 or claim 2 in which at least one of zone comprises a first active material and a second zone comprises a second active material and wherein the said active materials independently exhibit a release characteristic selected from immediate release, fast release, sustained release, delayed release, controlled release and pulsatile release.

6. A solid form according claim 1 or claim 2 in which at least one of the first zone or second zone of said compacted fill material is in the form of a layer.

7. A solid form according to claim 6 wherein at least one of said layers is a processing aid layer.

8. A solid form according to claim 6 wherein at least one of said layers is selected from an anti-sticking layer, a cushioning layer and a bulking layer.

9. A solid form according to claim 6 wherein at least one of said layers comprises said at least one active material and said layer is an immediate release layer, a fast release layer, a sustained release layer, a controlled release layer, a delayed release layer or a pulsatile release layer.

10. A solid form according to claim 6 wherein at least one of said layers is selected from a separating layer, disintegrant layer, aesthetic layer or a stability enhancing layer.

11. A solid form according to claim 6 wherein at least one of said layers comprises a low dose active material.

12. A solid form according to claim 11 comprising a bulking layer in intimate contact with the low dose active layer.

13. A solid form according to claim 11 wherein said low dose active layer is entrapped between two bulking layers.

14. A solid form according to claim 6, wherein said active material is present in at least two layers.

15. A solid form according to claim 6, wherein said compacted fill material is present in said solid form in at least three layers.

16. A solid form according to claim 6, wherein each layer comprises an active material.

17. A solid form according to claim 1 or claim 2 wherein said at least one active material is a pharmaceutical active.

18. A solid form according to claim 17, 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.

19. A solid form according to claim 17 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.

20. A solid form according to claim 17 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, phenelzine, 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, tocamide, 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.

21. A solid form according to claim 17, 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, 4-aminophthalic acid;

clarithromycin, ranitidine and bismuth citrate;

bismuth subsalicylate, metronidazole and tetracycline;

montelukast and loratadine;

fexofenadine and pseudoephedrine;

Guaifenesin and pseudoephedrine.

22. A solid form according to claim 1 or claim 2 wherein the dose form contains at least one active material in an amount greater than 100 mg.

23. A solid form according to claim 1 or claim 2 wherein the dose form contains at least one active material in an amount less than 100 mg.

24. A solid form according to claim 1 or claim 2 wherein the tensile strength of the compacted fill material is less than 0.2 MPa.

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

26. A solid form according to claim 1 or claim 2, comprising a non-compacted fill material in a non-compacted zone interposed between the first and second zone whereby the compacted fill material within the first zone is physically separated from the compacted fill material of the second zone.

27. A solid form according to claim 26, wherein the non-compacted fill material is selected from at least one of polyethylene glycol, polyethylene oxide, polymethacrylates, polyvinyl alcohol, stearic acid, cetyl alcohol, hydrogenated oils, glyceryl behenate, glyceryl palmitostarate, glyceryl monostearate, waxes, or heat stable sugar alcohols.

28. A method of making a solid form according to claim 1 or claim 2 comprising at least one film enrobing a compacted fill material comprising:

i) providing a first film shaped to define an interior volume for holding said compacted fill material and having an open end;

ii) depositing via the open end a first zone of fill material to be compacted in the interior volume and optionally applying pressure to the fill material so as to compact the first zone of fill material;

iii) depositing a second zone of fill material to be compacted in the interior volume such that the interior volume comprises two zones of fill material wherein at least one of the fill material in the first or second zone comprises an active material;

iv) applying pressure to the fill material so as to compact the at least second zone of fill material so forming the said compacted fill material;

v) applying a second film over the said open end to close the said open end; and

vi) sealing the first and second film together to enrobe the compacted fill material and provide the solid form.

29. A method according to claim 28 wherein each zone is in the form of a layer.

30. A method according to claim 28 wherein at least two zones are deposited in a single step.

31. A method according to claim 28 wherein each zone is deposited sequentially and compacted after each deposition.

32. A method according to claim 28 wherein each zone is deposited sequentially and the zones are compacted in a single compaction step.

33. A method according to claim 28 comprising the step of forming a non-compacted zone between the first zone of fill material and the second zone of fill material.

34. A method according to claim 33 comprising the step of applying a non-compacted fill material to the surface of the fill material in the first zone and depositing the second zone of fill material onto the non-compacted fill material whereby the non-compacted fill material provides a physical barrier separating the fill material of the first and second zones.

35. A method according to claim 28, wherein at least one of the layers are deposited using a volumetric or a vacuum system.

36. 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.

37. A method of treatment of the human or animal body by 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 said compacted fill material is selected from a pharmaceutical product, a food product, a veterinary product, a cosmetic, an appetite suppressant, a detergent product and a nutraceutical product and comprises at least one active material, the said compacted fill material comprises at least a first zone and a second zone and the said solid form shows a weight loss that is less than 1% during a 30 minutes USP friability test USP 29 Test Number 1216.