Method for releasing nanosized particles of an active substance from a diffusion-controlled pharmaceutical composition for oral use

A method according to any of the preceding claims, wherein the water-insoluble active substance or the nanosized particles carrying the active substance have a water-solubility of at the most about 10 mg/ml in water at 37° C. such as, e.g., at the most about 7.5 mg/ml, at the most about 5 mg/ml, at the most about 3 mg/ml, at the most about 1 mg/ml, at the most about 0.5 mg/ml, at the most about 0.25 mg/ml, at the most about 0.1 mg/ml or at the most about 0.05 mg/ml.

A method according to any of the preceding claims, wherein the active substance is a therapeutically, prophylactically and/or a diagnostically active substance or a pharmaceutically acceptable salt, solvate or complex thereof.

A method according to any of the preceding claims, wherein the active substance is selected from the group consisting of nifedipine, felodipine, amiodipine, nisoldipine isradipine, amilodipine, nicardipine;

• most steroid hormones such as, e.g., estrogen, progesterone, testosterone and derivatives and analogues thereof such as desogestrel, mesterolon, ebnylestradiol, nandronlon;
• hormone antagonists such as tamoxifene, toremifene, flutamide, nilutamide;
• glucocorticoids such as, e.g., cortisone, hydrocortisone, fludrocortisone, fludocortisone, betametasone, prednisolone, budesonide, and neurological drugs such as carbamazepine. carisoprodol, prmidone, zonisamide, perphanazin, antidiabetic drugs such as glibenclamide, glimepiride, glipizide, and miscellaneous low soluble drugs such as sucralfate, padlitaxel, and acyclovir.

A method according to any of the preceding claims, wherein the active substance or the nano particles employed in the composition has a volume weighted median particle size of at most about 2000 nm such as, e.g., at the most about 1500 nm, at the most about 1000 nm, such as, e.g., from about 1 nm to about 1000 nm, from about 2 nm to about 750 nm, from about 5 nm to about 500 nm or from about 7.5 nm to about 500 nm, from about 10 nm to about 500 nm, from about 50 nm to about 500 nm, from about 75 nm to about 400 nm, or from about 100 nm to about 300 nm as measured by static light scattering/diffraction or dynamic light scattering.

A method according to any of the preceding claims, wherein the composition comprises one or more pharmaceutically acceptable excipients.

A method according to any of the preceding claims further comprising at least one pharmaceutically acceptable excipient selected from the group consisting of fillers, diluents, disintegrants, binding agents and lubricants.

A method according to any of the preceding claims further comprising one or more wetting agents, pH adjusting agents, surface active agents, stabilizing agents, preservatives, colouring agents and/or taste-masking agents.

A method according to any of the preceding claims, wherein the pharmaceutical composition is a solid dosage form for oral use.

A method according to any of the preceding claims, wherein the diffusion-controlled membrane comprises a substantially water-insoluble polymer selected from the group consisting of

• i) cellulose derivatives including cellulose esters such as, e.g. ethylcellulose, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, cellulose propionate, cellulose butyrate, cellulose valerate, nitrocellulose, ii) acrylic polymers such as, e.g., polymethyl methacrylate, poly(ethacrylate, methylmethacrylate, trimethylammonioethylmethacrylate chloride), poly(ethylacryiate, methylmethacrylate), iii)vinyl polymers such as e.g. polyvinyl polymers such as, e.g polyvinyl acetate, polyvinyl formal, polyvinylbutryl, vinyl chloride-vinyl acetate copolymer, ethylenevinyl acetate copolymer, vinyl chloride-propylene-vinyl acetate copolymer, polyvinyl chloride, polyvinyl chloride terpolymers, iv) other polymers such as e.g. polyethylenes, polypropylenes, polylsobutylenes, polycarbonates, polybutadienes, polyesters and other high molecular synthetic polymers and block- or copolymers and combinations thereof.

A method according to any of the preceding claims, wherein the diffusion-controlled membrane is applied on the composition in the form of a coating dispersion.

A method according to any of the preceding claims, wherein the diffusion controlled membrane comprises potassium hydrogen tartrate as a pore-forming substance.

A method according to any of the preceding claims for controlling the release of the active substance from the pharmaceutical composition.

A method for designing a pharmaceutical composition coated with a diffusion membrane, said composition releasing particles comprising the active substance at a predetermined rate, the method comprising determination of a suitable retardation factor (R), a suitable hydrodynamic coupling factor (H), a suitable thickness for the diffusion membrane (L) and suitable diffusion coefficients for the ingredients in tie composition and water by means of Equations I, II, III

A method for designing a pharmaceutical composition coated with a diffusion membrane, said composition releasing particles comprising the active substance at a predetermined rate, the method comprising simulating the release rate by varying retardation factor (R), hydrodynamic coupling factor (H), thickness of the membrane (L) and surface area of the composition (A) by means of equations I and III in order to determine which concentration of a pore-forming substance in the membrane and which concentration of a gradient former in the composition will give the predetermined rate.