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WO2009105049A1 - Compositions de comprimés oraux contenant du natéglinide et un système agent tensioactif-agent de réglage du ph - Google Patents

Compositions de comprimés oraux contenant du natéglinide et un système agent tensioactif-agent de réglage du ph Download PDF

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Publication number
WO2009105049A1
WO2009105049A1 PCT/TR2009/000029 TR2009000029W WO2009105049A1 WO 2009105049 A1 WO2009105049 A1 WO 2009105049A1 TR 2009000029 W TR2009000029 W TR 2009000029W WO 2009105049 A1 WO2009105049 A1 WO 2009105049A1
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WO
WIPO (PCT)
Prior art keywords
solid composition
oral solid
nateglinide
cellulose
mixtures
Prior art date
Application number
PCT/TR2009/000029
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English (en)
Inventor
Inan Sahin
Serap Odabasi
Nur Tasar
Pelin Sari
Selda Koluman
Original Assignee
Bilim Ilac Sanayi Ve Ticaret A.S.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Bilim Ilac Sanayi Ve Ticaret A.S. filed Critical Bilim Ilac Sanayi Ve Ticaret A.S.
Priority to EP09712103A priority Critical patent/EP2257278A1/fr
Publication of WO2009105049A1 publication Critical patent/WO2009105049A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]

Definitions

  • the present invention relates to pharmaceutical compositions comprising nateglinide in combination with a surfactant-pH adjusting agent system, and process for their preparation.
  • Nateglinide is indicated as monotherapy to lower blood glucose in patients with Type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM) whose hyperglycemia cannot be adequately controlled by diet and physical exercise and who. have not been chronically treated with other anti-diabetic agents.
  • Type 2 diabetes non-insulin dependent diabetes mellitus, NIDDM
  • Nateglinide is an amino acid (phenylalanine) derivative, which is chemically and pharmacologically distinct from other antidiabetic agents. Nateglinide is a rapid, short-acting oral insulin secretagogue.
  • pancreas islets Nateglinide-induced insulin secretion by pancreatic beta cells is glucose-sensitive, such that less insulin is secreted as glucose levels fall. Conversely, the coadministration of food or a glucose infusion results in an enhancement of insulin secretion.
  • nateglinide oral tablets ara available in 60mg, 120mg and 180mg strengths are marketed by Novartis under the trand name Starlix®.
  • Starlix® is also indicated for use in combination with metformin. In patients whose hyperglycemia is inadequately controlled with metformin, Starlix may be added to, but not substituted for, metformin.
  • Nateglinide is a white powder with a molecular weight of 317.43. It is freely soluble in methanol, ethanol, and chloroform, soluble in ether, sparingly soluble in acetonitrile and octanol, and practically insoluble in water.
  • Antidiabetics are decreasing either a post prandial blood glucose level or fasting blood glucose level to make it close to normal level.
  • nateglinide has been developed, and it is discribed in, for example, Japanese Patent Publication No. 15,221/1992 or Japanese Patent Laid-Open No.194,696/1998.
  • antidiabetics for decreasing a fasting blood glucose level to make it close to a normal level are dicribed in, for example, Kondo Nobuo, Nippon Rinsho, vol. 55,1997, extra ed., p.159 and the like.
  • the various crystalline forms are related to each other in that drying of one form may result in a transformation to another form, namely nateglinide Form A, B, D, E, F, G, H, I, J, K, L, M 1 N, Q, S, T, V, Z, ⁇ , ⁇ , ⁇ , ⁇ , Y and ⁇ .
  • Nateglinide is disclosed in Japanese Patent Application Laid Open No. 63-54321 (equivalent to EP-A-196222 and US 4,816,484) and in J.Med.Chem.32,1436.
  • the Japanese application describes how the compound may be crystalized from aqueous methanol to yield crystals having a melting point of 129 0 C to 13O 0 C. These crystals are in a crystalline form known as ⁇ B-Type' crystals.
  • the known B-Type crystals suffer from problems of instability, especially when subjected to pulvarization.
  • the insatability results in conversion of the B- Type crystals into other forms.
  • US 5,463,116 discloses a method of producing a crystalline form of nateglinide having improved stability ( H-Type) to pulverization, and is thus said to be more suitable for use in doage forms than those of the B-Type.
  • Teva patent application ( WO2004067496) provides for a novel crystalline forms of nateglinide, denominated pure Form-U.
  • Crystalline Form-U does not have any significant amounts of bound solvents, and is an anhydrate.
  • the term 'anhydrate' refers to having a a bound solvate level of less than about 2 % is measured by LOD (Loss on drying). The characterization of this anhydrate shows that it is stable towards grinding.
  • Torm U' is utilised interchangeable with ⁇ pure Form U' both referring to the novel form lacking a XRPD peak.
  • the Form U described in crystallization examples of the priority applications is pure Form U despite Figure 1 showing the XRPD of the impure form.
  • Form U polymorphically stable when stored for a period of at least about 6 months 40 0 C / 75 % RH, or about 25°C / 60 % RH.
  • Form U is polymorphically stable at least 6 months when stored at a temperature of about 55°C.
  • Nateglinide-containing preparations can not show the fast-acting short duration effect in decreasing blood glucose level ( fast-acting hypoglycemic agent), which is characteristic of nateglinide.
  • this drug should be of immediate-release property.
  • nateglinide The pharmacokinetic features of nateglinide may be attributable to its rapid intestinal absorbtion. Because nateglinide is an anionic compound with pKa 3.1, it exists predominantly in ionized form at the intestinal physiological pH of 6.5. Moreover, its chloroform/water partition coefficient is reported to be 0.2 at pH 6.8 (British Journal of Pharmacology, 137(3), 391-399,2002) indicating that it is scarcely lipophilic. These physicochemical features are incompatible with rapid absorbtion by passive diffusion, suggesting that nateglinide absorbed via a specific transport system(s) in the intestine.
  • nateglinide transport of nateglinide from the mucosal to serosal side of the Caco-2 Cell monolayer appears to be a passive difussion process and that there appears to be an 'absorbtion window' when the pH is the range of 5.5 to 7.0.
  • the relatively poor solubility of nateglinide in acidic pH and considerably higher solubility at higher pH. e.g., pH 6.8 phosphate buffer
  • surfactants are added to acidic media.
  • micronized drug particles exhibit enhanced solubility and consequently an improved bioavability.
  • Highly micronized drug particles possess poor flow properties and increased chances of re-agglomeration during processing.
  • re- agglomeration of micronized drug particles may be so problematic that the essential concept of enhancing solubility by increasing the effective surface area is defeated.
  • the most common approach is micronizing the particles to a few microns.
  • Nateglinide is poorly water soluble subtances and therefore capsules filled with nateglinide drug subtances powder of its low disintegrating ability.
  • nateglinide-containing preparations cannot show the fast-acting and short duration effect in decreasing blood glucose level (fast-acting hypoglycemic agent), which is characteristic of nateglinide.
  • the drug needs to be released rapidly from preparations and so improvement on a preparation has been required. Rapid disintegration may be of paramount significance in eliminating the erratic absorbtion behavior releated to co-administration with food, and may help eliciting a more benificial therapeutic effect.
  • nateglinide create unpredictable dissolution rates and lead to absorption problems.
  • the use of surfactants in pharmaceutical formulations to assist in disintegration and dissolution of drug material is well known.
  • Lachman et al. in Theory and Practice of Industrial Pharmacy, second edition, page 108-9 discloses the use of surface active agents or surfactants in almost every dosage form including liquids, semi-solids and solids.
  • the surfactants play an important role in the absorption and efficacy of certain drugs. It leads to a surprising and unexpected discovery of use of surfactants to enhance the solubility and dissolution of solid dose oral formulations of poorly soluble drugs like nateglinide.
  • nateglinide-containing preparations show the fast-acting short duration effect in decreasing blood glucose level ( fast-acting hypoglycemic agent), which is characteristic of nateglinide.
  • the present invention relates to a tablet composition containing nateglinide as the active ingredient and a surfactant-pH adjusting agent system.
  • composition may further include one or more pharmaceutically acceptable excipients including filler, binder, disintegrant, surfactant, pH adjusting agent, lubricant, glidant coloring agent and film forming agents.
  • pharmaceutically acceptable excipients including filler, binder, disintegrant, surfactant, pH adjusting agent, lubricant, glidant coloring agent and film forming agents.
  • the filler may be one or more of corn starch, lactose, mannitol, maltodextrin, sucrose, sugar compressible, sorbitol, calcium carbonate, magnesium carbonate, calcium phosphate- dibasic, calcium phosphate-tribasic, calcium sulphate, microcrystalline cellulose, silificied microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose, fructose and mixtures thereof.
  • the binder may be one or more of polyvinylpyrrolidone, methyl cellulose, hydroxypropyl cellulose, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pregelatinezed starch, agar, tragacanth, sodium alginate, propylene glycol, and mixtures thereof.
  • the disintegrant may be one or more of crospovidone, copovidone, sodium starch glycolate, croscarmellose sodium, polacrilin potassium, starch derivates, hydroxypropyl cellulose and mixtures thereof.
  • the surfactant may be one or more of sodium lauryl sulphate, potassium dodecyl sulphonate, sodium dodecyl benzene sulphonate, sodium salt of lauryl polyoxyethylene sulphate, lauryl polyoxyethylene oxide sulphate, lauryl polyethylene oxide sulphonate, dioctyl ester of sodium sulphosuccinic acid or sodium lauryl sulphonate, polysorbate derivates, nonyl phenol polyoxyethylene ether, tridecyl alcohol poyoxyethylene ether, dodecyl mercaptane polyoxyethylene thioether, the lauric ester of polyetylene glycol, the lauric ester of sorbitan polyoxyethylene ether or tertiary alkyl amine oxide, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, stearyl trimethyl ammonium chloride, cetyl pry
  • the pH adjusting agent may be one or more of acetic acid, ammonia solution, monoethanole amine, diethanoleamine, triethanoleamine meglumine, sodium citrate, citric acid, hhdrochloric acid, lactic acid, phospharic acid, propionic acid, sulphiric acid, tartaric acid, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium bicarbonate, sodium borate, sodium hydroxide and mixtures thereof.
  • the lubricant may be one or more of, calcium stearate, glycerin mono stearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, magnesium lauryl sulphate, magnesium stearate, medium-chain triglycerides, myristic acid, sodium stearyl fumarate, stearic acid, talc, zinc stearate and mixtures thereof.
  • the glidant may be one or more of calcium silicate, collidal silicon dioxide, silicon dioxide, magnesium silicate, magnesium trisilicate, talc and mixtures thereof.
  • the film forming agents may be one or more of ethyl cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxymetyhl cellulose, hyroxyethyl cellulose, hydroxypropylmethyl phthalate, cellulose acetate, cellulose acetate trimelliatate, cellulose acetate phthalate; waxes such as polyethylene glycol; methacrylic acid polymers marketed such as trade names Eudragit® E and S; and the like and mixture thereof.
  • coomercial available coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry® may also be used for coating.
  • Eudragit® E is the trade name of dimethylamino methacrylate-notralized methacrylate copolymer.
  • Eudragit® S is the trade name of methacrylicacid copolymer ( Type A, USP/NF)
  • Opadry® is generally containing film forming agents such as; hydroxypropylmethyl cellulose, propylene glycol, polyvinyl alcohol, ethyl cellulose, methyl cellulose and additionaly color pigments, plasticizer and antiadherent materials.
  • Suitable coloring agents include on or more FDA approved colors for oral use.
  • the compositions of nateglinide may be prepared by processes known in the prior art including mixing, granulation, melting, sieving, filling, dryig, molding, immersing, coating, compressing, extrusion-spheronization, etc.
  • the oral solid composition of nateglinide may be prepared by processes, for example, wet granulation, dry granulation or direct compression and may be in the form of tablets or capsules.
  • the processes of direct compression may include preparing a blend of nateglinide, surfactant, filler, disintegrant, binder, lubricant and glidant; and compressing the blend into a tablet.
  • the process of dry granulation may be carried out by slugging or roller compaction.
  • the composition of nateglinide may be prepared by the process of blending nateglinide, surfactant, filler, disintegrant and binder; compacting or slugging the blend; breaking the slugs to make granules; lubricating and compressing the lubricated granules.
  • the process of wet granulation may be carried out by blending nateglinide, surfactant, pH adjusting agent, filler and disintegrant; and granulating the blend with a solution/dispersion of the binder.
  • nateglinide, filler, disintegrant, binder and glidant; and the granulating the blend wtih a solution/disoersion of the surfactant and pH adjusting agent.
  • the granules are dried and may be mixed with other excipients like disintegrant, lubricant, glidants, extra-granular filler and coloring agents and compressed with a suitable punches into tablets.
  • the granulation may also be carried out in a fluidized bed-dryer and siezing may be done by milling or pulverizing.
  • the tablets prepared by the present invention may be considered may be coated one or more additional layers of film forming agents and/or pharmaceutically acceptable excipients.
  • the coating layers over the tablet may be applied as solution/dispersion of coating ingredients using any conventional technique known in the prior art such as spray- coating in a conventional coating pan or fluidized pan processor; and dip coating.
  • Suitable solvents used for preparing a solution/dispersion of the coating ingredients includes methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, water and mixtures thereof.
  • 'nateglinide' as used herein includes nateglinide in a free or pharmaceutically salt form, in crystalline or amorphous form.
  • the nateglinide may be the-U type crystal modification.
  • the active ingredients or a pharmaceutically acceptable salt thereof may also be used in form of a hydrate or solvates thereof.
  • the amount of nateglinide to be used may vary from about 5% to 70% (w/w), and in particular, from about 15% to about 40% (w/w) of the total pharmaceutical composition.
  • filler or is a bulking agent, providing a quantity of material which can accurately be formed into a tablet. Fillers fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. By increasing the bulk volume, the final product has the proper volume for patient handling.
  • the amount of filler to be used may vary from about %15-%90 (w/w).
  • binder' are used in pharmaceutical solid formulations to add cohesiveness to poisers, thereby providing the necessary bonding to form granules, which under compaction form a cohesive mass or compact referred to as a tablet.
  • the formation of granules aids in the conversion of powders-of widely varying particle sizes-to granules, which may more uniformly flow from the hopper to the feed system, and uniformly fill the die cavity.
  • the amount of binder to be used may vary from about % 0,5 to about %10 (w/w). And in particular from about 0,5 % to about 5 % (w/w), of the total pharmaceutical composition.
  • disintegrants' as used herein includes a substance that facilitate the breakup of a tablet after administration. Disintegrating agents may be added prior to granulation or during the lubrication step prior to compression or at borh processing steps. The amount of disintegrant to be used may vary from about % 0,5 to about %10 (w/w).
  • surfactans' as used herein includes a substance that lowers the surface tension of the medium in which it is dissolved, and/or the interfacial tension with other phases, and, accordingly, is positively adsorbed at the liquid/vapor and/or at other interfaces.
  • Suitable surfactans include one or more of anionic, noionic, cationic and mixtures thereof.
  • the nonionic surfactans have a hydrophobic/hydrophilic balance wherein there is neither a negative nor a positive charge in either part of the molecule, thus giving it the nonionic terminology.
  • the amount of surfactant to be used may vary from about % 0,5 to about %10 (w/w). And in particular from about 0,5 % to about 3 % (w/w), of the total pharmaceutical composition.
  • ⁇ pH adjusting agent' as used herein includes a substance that adjust the pH of pharmaceutical forms to intended use. Also they have the function of solubility enhancing activity by increasing or decreasing the pH of the medium which can be site of action and/or buffer solutions.
  • 'lubricants' as used herein includes a substance that reduce the friction arising at the interface of tablet and the die wall during compression and ejection.
  • the amount of lubricant to be used may vary from about % 0,25 to about %5 (w/w). And in particular from about 0,25 % to about 2 % (w/w), of the total pharmaceutical composition.
  • v glidants' as used herein includes a substance that improves flow characteristics of the granulation, Gidants can improve the flow of granulations from hoppers into feed mechanism and ultimately into the die cavity.
  • the amount of disintegrant to be used may vary from about % 0,25 to about %8 (w/w). And in particular from about 0,25 % to about %5 (w/w), of the total pharmaceutical composition.
  • the absorbtion window of nateglinide ( pH 5.5 to 7.0) and the ionization of the drug in the intestinal phsiological pH 6.5 make the dissolution behavior of nateglinide in alkaline pH, more important for the in-vivo bioavability.
  • nateglinide when used with a combination of surfactant-pH adjusting system in a tablet formulation, the dissolution propeties of nateglinide in alkaline pH improve, and there is no lack of discrimination between samples manufactured with varying process parameters and also the dissolution of tablets apperars to be disintegration based on visiual inspection.
  • micronized nateglinide particles exhibit enhanced solubility by increasing the effective surface area. Highly micronized nateglinide particles possess poor flow properties and increased chances of re-agglomeration during processing. We have found the optimal particle size distrubition of micronized nateglinide that does not have any negative effect on solubility and process.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (d 9 o ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (d 90 ⁇ 150 ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (dgo ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (dg O ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the- bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (dg 0 ⁇ 150 ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture,
  • Step 2 Deionized water ,polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (dg O ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (dg O ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Concentration may be adjusted to maintain constant tablet weight based on the quantity of nateglinide potency.
  • Nateglinide (d 9 o ⁇ 15O ⁇ m), lactose, polyvinylpyrrolidone, croscarmellose sodium, colloidal silicon dioxide are passed through a screen and than mixed in a high shear blender to give a uniform dry mixture.
  • Step 2 Deionized water, polysorbate 80 and meglumine are added slowly to the dry mixture of Step 1 under fast mixing in a high shear mixer granulator and the bulk is then granulated.
  • the wet granules are dried in a drying oven/fludized bed dryer, passed through a screen.
  • Dissolution media 0.01N HCI (including 0.5 % SLS)
  • Dissolution media pH 4.5 acetate buffer (including 0.25 % SLS)
  • Dissolution media pH 6.8 phosphate buffer (including 0.1 % SLS)
  • Mobil Phase 450.0 mL pH 2.3 buffer and 550.0 mL Acetonitril R are mixed and degased by filtering through 0.20 ⁇ m filter.
  • Dissolution profiles is compared using the above similarity factor.
  • R t and T t is the % dissolved drug in a time point of the Reference Product and the Test Product.
  • the dissolution profile can be expected as similar when the ⁇ f 2 ) result is between 50 to 100.
  • Dissolution profile of Example 5 and referance product in 0.01N HCI dissoluion media is given in Figure 2.
  • Dissolution profile of Example 5 and referance product in pH 4.5 dissoluion media is given in Figure 3.
  • Dissolution profile of Example 5 and referance product in pH 6,8 dissoluion media is given in Figure 4.

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Abstract

La présente invention concerne des préparations pharmaceutiques qui contiennent du natéglinide et un système agent tensioactif:agent de réglage du pH et leurs procédés de préparation. Une composition solide orale comprend : a) du natéglinide ou des sels pharmaceutiquement acceptables de celui-ci ; et b) au moins un système d’agent tensioactif-agent de réglage du pH pharmaceutiquement acceptable qui est produit par les étapes de mélange du natéglinide, d’une ou plusieurs charges, d’un délitant, d’un liant et d’un glissant, de granulation avec le système d’agent tensioactif:agent de réglage du pH, de séchage, de broyage, de lubrification, de mise en comprimé et de revêtement de film.
PCT/TR2009/000029 2008-02-22 2009-02-20 Compositions de comprimés oraux contenant du natéglinide et un système agent tensioactif-agent de réglage du ph WO2009105049A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09712103A EP2257278A1 (fr) 2008-02-22 2009-02-20 Compositions de comprimés oraux contenant du natéglinide et un système agent tensioactif-agent de réglage du ph

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2008/01178A TR200801178A2 (tr) 2008-02-22 2008-02-22 Nateglinid ve surfaktan-ph ayarlayıcı sistemi içeren oral tablet kompozisyonları
TR2008/01178 2008-02-22

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WO2009105049A1 true WO2009105049A1 (fr) 2009-08-27

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2633857B1 (fr) 2009-12-23 2015-08-12 ratiopharm GmbH Forme de dosage solide pharmaceutique de ticagrelor et de l'acide acétylsalicylique

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334720A1 (fr) * 2000-10-24 2003-08-13 Ajinomoto Co., Inc. Preparations contenant du nateglinide
WO2004067496A1 (fr) * 2003-01-23 2004-08-12 Teva Pharmaceutical Industries Ltd. Forme cristalline de nateglinide
WO2005051360A1 (fr) * 2003-11-28 2005-06-09 Ranbaxy Laboratories Limited Compositions pharmaceutiques comprenant de la nateglinide et un agent tensioactif
WO2005092319A1 (fr) * 2004-03-29 2005-10-06 Ranbaxy Laboratories Limited Compositions pharmaceutiques a desintegration rapide, comprenant du nateglinide et un delitant
US20060127475A1 (en) * 2003-08-08 2006-06-15 Ajinomoto Co., Inc. Nateglinide-containing preparation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334720A1 (fr) * 2000-10-24 2003-08-13 Ajinomoto Co., Inc. Preparations contenant du nateglinide
WO2004067496A1 (fr) * 2003-01-23 2004-08-12 Teva Pharmaceutical Industries Ltd. Forme cristalline de nateglinide
US20060127475A1 (en) * 2003-08-08 2006-06-15 Ajinomoto Co., Inc. Nateglinide-containing preparation
WO2005051360A1 (fr) * 2003-11-28 2005-06-09 Ranbaxy Laboratories Limited Compositions pharmaceutiques comprenant de la nateglinide et un agent tensioactif
WO2005092319A1 (fr) * 2004-03-29 2005-10-06 Ranbaxy Laboratories Limited Compositions pharmaceutiques a desintegration rapide, comprenant du nateglinide et un delitant

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2633857B1 (fr) 2009-12-23 2015-08-12 ratiopharm GmbH Forme de dosage solide pharmaceutique de ticagrelor et de l'acide acétylsalicylique
EP2515871B1 (fr) 2009-12-23 2015-09-23 ratiopharm GmbH Forme de dosage solide pharmaceutique de ticagrlor

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TR200801178A2 (tr) 2009-09-23

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