JP2009537456A5

JP2009537456A5 -

Info

Publication number: JP2009537456A5
Application number: JP2008539368A
Authority: JP
Filing date: 2006-05-24
Publication date: 2009-12-10
Anticipated expiration: 2026-05-24

Claims

Including means to avoid misuse,
At least a portion of the active ingredient (AI) included in the pharmaceutical form is included in the coated microparticles for modified release of AI,
AI coated fine particles
At least one film-forming (co) polymer (A1) that is insoluble in the fluid of the gastrointestinal tract;
At least one (co) polymer (A2) that is soluble in the fluid of the gastrointestinal tract;
At least one plasticizer (A3);
Any at least one surfactant and / or lubricant and / or mineral and / or organic filler (A4)
Comprising at least one coating layer (Ra) comprising
Oral and solid pharmaceutical forms, characterized in that the layer enables modified release of AI and at the same time imparts crush resistance to the coated microparticles to avoid misuse.

The pharmaceutical form according to claim 1, characterized in that the coating layer (Ra) represents a mass concentration Tp expressed as a dry weight% relative to the total mass of the coated microparticles such that Tp ≧ 15.

The pharmaceutical form according to claim 1 or 2, wherein the AI-coated microparticles have an average diameter of 1000 µm or less.

In order to avoid misuse, characterized in that it contains at least one thickener (Vb) suitable for preventing the extraction of AI contained in AI coated microparticles for modified release of AI, The pharmaceutical form according to any one of claims 1 to 3.

Pharmaceutical form according to any one of claims 1 to 4, characterized in that it comprises at least one sequestering agent (Q) suitable for complexing with AI in solution.

In the case of milling, the coating layer (Ra) is designed to make it possible to maintain a modified release of AI for at least some of the coated particles, preferably at least 40% of the particles. The pharmaceutical form according to any one of claims 1 to 5.

The coating layer (Ra) is the following (expressed in% by weight relative to the total mass of the coating):
10 ≦ A1 ≦ 90;
5 ≦ A2 ≦ 50;
1 ≦ A3 ≦ 30;
0 ≦ A4 ≦ 40
The pharmaceutical form according to any one of claims 1 to 6, characterized in that

(A1) is
Water-insoluble cellulose derivatives, such as ethyl cellulose, and / or cellulose acetate,
Acrylic polymers, such as copolymers of (meth) acrylic acid and alkyl (e.g. methyl) esters, copolymers of acrylic acid and methacrylic acid esters having at least one quaternary ammonium group,
Polyvinyl acetate,
As well as selected from the group of mixtures thereof;
(A2) is
Nitrogen-containing (co) polymers,
Water-soluble cellulose derivatives ,
Polyvinyl alcohol (PVA),
Alkylene polyoxide,
Polyethylene glycol (PEG),
As well as selected from the group of mixtures thereof;
(A3) is
Cetyl alcohol ester,
Glycerol, and its esters,
Phthalates,
Citrate,
Sebacate,
Adipate,
Azelate,
Benzoate,
Vegetable oil,
Fumarate,
Malate,
Oxalate,
Succinate,
Butyrate,
Cetyl alcohol ester,
Triacetin,
Malonate,
Castor oil,
As well as selected from the group comprising mixtures thereof;
(A4) is
Anionic surfactants,
And / or preferably the following subgroups:
Polyoxyethylenated oil, preferably polyoxyethylenated hydrogenated castor oil,
Polyoxyethylene / polyoxypropylene copolymer,
Polyoxyethylenated sorbitan ester,
Polyoxyethylenated castor oil derivative,
Nonionic surfactant stearates from, preferably calcium, magnesium, aluminum or zinc stearate,
Stearyl fumarate, preferably sodium stearyl fumarate,
Glycerol behenate,
Talc powder,
Colloidal silica,
Titanium oxide, magnesium oxide,
Bentonite,
Microcrystalline cellulose,
Kaolin,
Aluminum silicate,
As well as selected from the group of mixtures thereof,
The pharmaceutical form according to any one of claims 1 to 7.

The thickener (Vb) is a polyoxyethylene having a high molecular weight of 1 to 8 million g / mol, which is suitable for increasing the viscosity of the extract and preventing misuse especially by injection. The pharmaceutical form according to claim 4.

Thickener (Vb) is the next group of polymers:
Polyacrylic acid, and derivatives thereof, and / or polyalkylene glycol (e.g. polyethylene glycol), and / or polyalkylene oxide (e.g. polyethylene oxide), and / or polyvinyl pyrrolidone, and / or gelatin, and / or polysaccharide, e.g. Sodium alginate, pectin, guar, xanthan, carrageenan, gellan, and cellulose derivatives,
And the pharmaceutical form according to claim 4, characterized in that it is selected from the group of polymers of as well as mixtures thereof.

11. The pharmaceutical form according to any one of claims 5 to 10, characterized in that it comprises AI salt microparticles and different sequestering agent (Q) microparticles.

The pharmaceutical form according to claim 11, characterized in that the microparticles have a close size distribution, close density and cannot be separated from each other by sieving.

Sequestering agent (Q)
Anionic organic salts such as sodium dodecyl sulfate or sodium docusate;
(Meth) acrylic copolymers (e.g. Eudragit® S and Eudragit® L), cross-linked polyacrylic acid (e.g. Carbopol), carboxymethyl cellulose and its derivatives, cross-linked carboxymethyl cellulose and its derivatives, and other polysaccharides (e.g. Anionic polymers such as alginate, xanthan gum, or gum arabic), and propylene glycol alginate (sulfonate);
Monovalent or polyvalent salts such as glucuronate, citrate, acetate, carbonate, gluconate, succinate, phosphate, glycerophosphate, lactate, trisilicate, fumarate, adipate, benzoate, salicylate, tartrate, sulfonamide, acesulfame;
Saponified fatty acids such as acetate, succinate, citrate, stearate, palmitate and self-emulsifying glyceryl monooleate;
Polyamino acids, proteins or peptides such as albumin, casein, globulin, and enzymes;
A pharmaceutical form according to any one of claims 5 to 12, characterized in that it comprises a salt selected from the group of mixtures thereof.

Sequestering agent (Q)
For example, acesulfame, acetate, adipate, benzoate, carbonate, chloride, citrate, fluoride, fumarate, gluconate, glucuronate, glycerophosphate, hydroxide, iododate, iodide, lactate, oxide, phosphate, trisilicate, salicylate, succinate, sulfone Cationic salt of metal Ca, Fe, Mg or Zn in the form of amide or tartrate;
An organic cation salt, such as a quaternary ammonium salt, such as tetradecyltrimethylammonium bromide or benzethonium chloride;
Cationic polymers such as chitosan and (meth) acrylic copolymers (e.g. Eudragit® RS, Eudragit® RL or Eudragit® E);
Polyamino acids, proteins or peptides;
A pharmaceutical form according to any one of claims 5 to 12, characterized in that it comprises a salt selected from the group of mixtures thereof.

Sequestering agent (Q)
Anionic organic salts such as sodium dodecyl sulfate or sodium docusate;
Cationic organic salts such as quaternary ammonium salts;
The pharmaceutical form according to any one of claims 5 to 12, characterized in that it is selected from strong acid cation exchange resins or strong base anion exchange resins depending on the polarity of AI.

Sequestering agent (Q)
Strongly acidic cation exchange resins and mixtures thereof when AI is cationic;
The pharmaceutical form according to claim 5, characterized in that when AI is anionic, it is selected from strongly basic anion exchange resins and mixtures thereof.

The sequestering agent (Q) is in the form of fine particles that cannot be separated from the fine particles of AI, whether coated or uncoated. A pharmaceutical form according to 1.

Thickener (Vb) fine particles, or metal ion sequestering agent (Q) fine particles, or thickener (Vb) fine particles, and metal ion sequestering agent (Q) fine particles, and thickener (Vb) fine particles The pharmaceutical form according to any one of claims 3 to 16, wherein the fine particles and the fine particles of the sequestering agent (Q) are different from the fine particles of AI.

AI fine particles and thickener (Vb) fine particles, or
AI fine particles and sequestering agent (Q) fine particles, or
Including fine particles of AI, fine particles of thickener (Vb), and fine particles of sequestering agent (Q), the fine particles have a close size distribution and close density, and cannot be separated from each other by sieving A pharmaceutical form according to any one of claims 5 to 17.

The AI used is characterized in that it is selected from the group consisting of oxycodone hydrochloride, morphine sulfate, oxymorphone hydrochloride, hydromorphone hydrochloride, hydrocodone hydrochloride, and tramadol hydrochloride. Pharmaceutical form as described in any one of these.

21. A pharmaceutical form according to any one of the preceding claims, characterized in that it has no AI antagonist agent.

Use of the microparticles as defined in claims 1 to 20 for the manufacture of a pharmaceutical form.

21. Use of microparticles as defined in claims 1 to 20 which provide a pharmaceutical form comprising AI properties and avoids misuse of said AI.