Solid, Oral Drug Form Which Has Been Designed to Prevent Misuse

• US 20080193540A1
• Filed: 11/21/2005
• Published: 08/14/2008
• Est. Priority Date: 11/23/2004
• Status: Abandoned Application

• Current Assignee: Flamel Technologies SA (Avadel Pharmaceuticals Plc)
• Original Assignee: Flamel Technologies SA (Avadel Pharmaceuticals Plc)
• Inventors: Soula, Gerard, Dargelas, Frederic
• Application Number:
  US11/791,336
• Publication Number:
  US 20080193540A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention relates to the field of solid medicaments that are intended for the oral administration of active ingredients. The aim of the invention is to prevent the improper use of solid, oral medicaments for any user other than the therapeutic use(s) officially approved by the appropriate public health authorities. More specifically, the invention relates to a solid, oral drug form which is characturised in that it comprises: A) at least one caking agent; and B) at least one viscosifying agent, such as to prevent the misuse thereof.

Claims

1. A solid oral drug form, characterized in that it comprises:

C) at least one caking agent,

and

D) at least one viscosifying agent;

so as to prevent misuse.

2. The drug form as claimed in claim 1, characterized in that all or part of the AI of this drug form is contained in microparticles.

3. The drug form in particular as claimed in claim 1 or 2, characterized in that it comprises inert insoluble beads which have an average diameter of greater than or equal to 1.25 times, preferably 1.5 times, and even more preferably twice, the average diameter of the microparticles of AI.

4. The drug form as claimed in one of the preceding claims, characterized in that the caking agent A) is chosen from those capable of ensuring, in the event of crushing of the drug form, that the latter is converted into a nonpulverulent product.

5. The drug form as claimed in claim 1 or 4, characterized in that the caking agent A) is chosen from the class of hydrophobic compounds that act as a dry binder, preferably:

from the group comprising cottonseed oils, soybean oils, palm oils, castor oils and mixtures of all or some of these oils; and

/or

from the group of waxes, and even more preferably from the subgroup of waxes comprising hydrogenated cottonseed oils, hydrogenated soybean oils, hydrogenated palm oils, glyceryl behenates, hydrogenated castor oils, tristearins, tripalmitins, trimyristins, yellow waxes, hard fats, anhydrous dairy fats, lanolins, glyceryl palmitostearates, glyceryl stearates, lauric acid macrogolglycerides, cetyl alcohols, polyglyceryl diisostearates, diethylene glycol monostearates, ethylene monostearates, omegas 3 and mixtures of all or some of these waxes; and

/or

from the group of fatty bases for suppositories comprising glycerol, triglycerides, theobroma oils, cacao butters and mixtures of all or some of these products.

6. The drug form as claimed in any one of the preceding claims, characterized in that it cannot be converted into a dry form that can be administered by nasal aspiration.

7. The drug form as claimed in any one of the preceding claims, characterized in that the viscosifying agent B) is chosen from those capable of rendering noninjectable the AI contained in the drug form.

8. The drug form as claimed in any one of the preceding claims, characterized in that the viscosifying agent B) is chosen from the following group of polymers:

polyacrylic acids and derivatives thereof, and/or

polyalkylene glycols (e.g. polyethylene glycol), and/or

polyvinylpyrrolidones, and/or

gelatins, and/or

polysaccharides, preferably from the subgroup comprising;

sodium alginate, pectins, guars, xanthans, carrageenans, gellans and cellulose derivatives (e.g. hydroxypropylmethylcellulose, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose),

and mixtures thereof.

9. The drug form as claimed in any one of the preceding claims, characterized in that it cannot be converted into an injectable form.

10. The drug form as claimed in claim 3, characterized in that the insoluble neutral beads are chosen from the group of following substances:

celluloses and insoluble derivatives thereof, polymethacrylic resins and derivatives thereof, silicas, talc, semolina, bentonite and mixtures thereof.

11. The drug form as claimed in any one of the preceding claims, characterized in that it comprises immediate-release AI and/or modified-release AI.

12. The drug form as claimed in claims 3 and 11, characterized in that at least some of the microparticles are microcapsules for modified release of AI.

13. The drug form as claimed in claim 2 or 12, characterized in that the microparticles or the microcapsules have an average diameter of less than or equal to 1000 μ

m, preferably less than or equal to 500 μ

m, and more preferably a diameter of less than or equal to 300 μ

m.

14. The drug form as claimed in any one of the preceding claims, characterized in that the extraction of the AI by chewing and/or crushing is not effective.

15. The drug form as claimed in any one of the preceding claims, characterized in that the AI used belongs to at least one of the following families of active substances:

amphetamines, analgesics, appetite suppressants, antidepressants, antiepileptics, antimigraine agents, antiparkinsonian agents, antitussives, anxiolytics, barbiturates, benzodiazepines, hypnotics, laxatives, neuroleptics, opiates, psychostimulants, psychotropic agents, sedatives and stimulants.

16. The drug form as claimed in one of the preceding claims, characterized in that the AI used is chosen from the following compounds:

methylphenidate, Fentanyl, Alfentanyl, Pentazocine, Pethidine, Phenoperidine, Remifentanil, Sufentanil, Acetorphine, Acetylalphamethylfentanyl, Acetylmethadol, Alfentanil, Allylprodine, Alphacetylmethadol, Alphameprodine, Alphamethadol, Alphamethylfentanyl, Alpha-methylthiofentanyl, Alphaprodine, Anileridine, atropine, Benzethidine, Benzylmorphine, Beta-hydroxyfentanyl, Beta-hydroxymethyl-3-fentanyl, Betacetylmethadol, Betameprodine, Betamethadol, Betaprodine, Bezitramide, buprenorphine, Dioxaphentyl butyrate, Cannabis, Ketobemidone, Clonitazene, codeine, Coca, Cocaine, Codoxime, Concentrate of poppy straw, Desomorphine, Dextromoramide, Diampromide, Diethylthiambutene, Difenoxine, Dihydroetorphine, Dihydromorphine, Dimenoxadol, Dimepheptanol, Dimethylthiambutene, Diphenoxylate, Dipipanone, Drotebanol, Ecgonine, ephedrine, Ethylmethylthiambutene, Etonitazene, Etorphine, Etoxeridine, Fentanyl, Furethidine, Heroin, Hydrocodone, Hydromorphinol, Hydromorphone, Hydroxypethidine, . Isomethadone, Levomethorphane, Levomoramide, Levophenacylmorphane, Levorphanol, meperidine, Metazocine, Methadone, Methyldesorphine, Methyldihydromorphine, Methyl-3-thiofentanyl, Methyl-3-fentanyl, Metopon, Moramide, Morpheridine, morphine, MPPP, Myrophine, Nicomorphine, Noracymethadol, Norlevorphanol, Normethadone, Normorphine, Norpipanone, Opium, Oxycodone, Oxymorphone, Para-fluorofentanyl, PEPAP, Pethidine, Phenampromide, Phenazocine, Phenomorphane, Phenbperidine, Piminodine, Piritramide, Proheptazine, propanolol, Properidine, Racemethorphane, Racemoramide, Racemorphane, Remifentanil, Sufentanil, Thebacone, Thebaine, Thiofentanyl, Tilidine, Trimeperidine, Acetyldihydrocodeine, Codeine, Dextropropoxyphene, Dihydrocodeine, Ethylmorphine, Nicocodine, Nicodicodine, Norcodeine, Pholcodine, Propiram,

and mixtures thereof.