Pharmaceutical composition at delayed release of pharmaceutically active substance and method for releasing pharmaceutically active substance

FIELD: pharmaceutics.

SUBSTANCE: the suggested pharmaceutical composition at delayed release contains fluvastatin or its pharmaceutically acceptable salt hydroxypropylmethylcellulose and nonionic hydrophilic polymer. The latter is being hydroxyethylcellulose at average molecular weight ranged 90000-1300000 or hydroxypropylcellulose at average molecular weight ranged 370000-1500000 or polyethylenoxide at average molecular weight ranged 100000-500000. The suggested pharmaceutical composition is necessary to obtain peroral medicinal remedy for decreasing cholesterol level in plasma, it, also, provides the supply of fluvastatin into the body during prolonged period of time, for example, for more than 6 h and enables to minimize the possibility for premature release or "discharge" of considerable fluvastatin quantities.

EFFECT: higher efficiency.

21 cl, 6 dwg, 5 ex, 5 tbl

 

The technical field to which the invention relates.

The present invention relates to intended for oral administration of pharmaceutical compositions with delayed release of pharmaceutically active substances.

Background of invention

Normal intended for oral administration the pharmaceutical composition with delayed release of pharmaceutically active substances are used for a number of reasons. Such compositions provide the intake of pharmaceutically active substances for a long period of time in contrast to the compositions with the unregulated release or immediate release of pharmaceutically active substances which, when used pharmaceutically active substance enters the body within a short time interval immediately after taking the drug. Therefore, the immediate release of the active substance, its concentration in the patient's body quickly reaches a maximum value and then falls below therapeutically effective values, and therefore the composition with the unregulated release is usually taken several times a separate doses during the day. Conventional pharmaceutical composition with delayed release of pharmaceutically active substances have on the certain advantages over compositions with the unregulated release, because they allow you to reduce the frequency of taking the drug in a given period of time, for example to take the drug at once, and not repeated dosing, which in turn may improve compliance in patients prescribed regime and regimen, as well as maintain a more stable concentration of active substance in the blood for a longer period of time.

Although pharmaceutical composition with delayed release of pharmaceutically active substances are generally limited to a single introduction of such dose of the active substance, which is necessary to ensure its entry into the body within a specified period of time, for example a single reception daily dose, their application may result in a sudden release of significant quantities of active substances. For a number of reasons such premature release or "release" pharmaceutically active substances can reduce the overall therapeutic efficacy of the active substance entering the body. One of these problems occurs when the body, which receives the active substance, processes it with constant speed. Accordingly, in the premature release of the active substance exceeds that which the body of the method is to process within a specified period of time, i.e. the body "overloaded" active substance. Consequently, a large portion of the active substances may enter the body and not interacting with him, essentially lost to the body of the patient without the target therapeutic effect.

In the patent US 5376383 in example 8 described matrix delivery system containing lovastatin as terapevticheskogo agent, hydroxypropylcellulose (KLUCEL® LF) and hypromellose (METHOCEL® ES and METHOCEL® K15M). According to the producers molecular weight KLUCEL® LF is approximately 95,000. If this is not known, does KLUCEL® LF at such a low value of the molecular weight of any effect on the release profile of matrix delivery system. In the mentioned patent says nothing about the release profile immediately after drug administration.

Based on the foregoing, there is a need to develop such a composition, which, while maintaining all of the advantages inherent in conventional pharmaceutical compositions with delayed release of pharmaceutically active substances, would at the same time to minimize the possibility of premature release of significant quantities of the active substance.

Brief description of drawings

Attached to the description of the drawings shows:

figure 1 - graph showing the dependence is the cost of dissolving the composition in water from time to time with different content of hydroxypropylmethylcellulose in the song,

figure 2 - graph showing the dependence of dissolution of the composition in acetate buffer with pH 4.0 from time to time,

figure 3 is a graph showing the dependence of dissolution of the composition in phosphate buffer pH 6.8 from time to time,

figure 4 is a graph showing the dependence of dissolution of the composition in water from time to time,

figure 5 - graph showing the time dependence of dissolution in phosphate buffer with pH 6.8 pharmaceutical compositions containing as hypromellose and hydroxypropylcellulose, and

figure 6 - graph showing the time dependence of dissolution in phosphate buffer with pH 6.8 compositions containing hypromellose, but not containing hydroxypropylcellulose.

Brief description of the invention

The object of the invention is a pharmaceutical composition comprising a pharmaceutically active substance, hypromellose and non-ionic hydrophilic polymer selected from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of 90000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 370000 to 1,500,000 and polyethylene oxide with srednekamennogo molecular weight of from 100000 to 500000.

Another object of the invention is a method of release of the pharmaceutically active substance in the body of a mammal, comprising errorline introduction into the organism of a mammal pharmaceutically active ingredients of the pharmaceutical composition, containing a pharmaceutically active substance, hypromellose and non-ionic hydrophilic polymer selected from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of 90000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 370000 to 1,500,000 and polyethylene oxide with srednekamennogo molecular weight of 370000 to 500,000.

Detailed description of the invention

It has been unexpectedly found that compositions which along with hypromellose (hereinafter GPMC) contain at least one non-ionic hydrophilic polymer, prevents premature release of the pharmaceutically active substance of this composition. The concept of "premature release" in the context of the present description means the release of significant amounts of pharmaceutically active substances for a short period of time after administration of the composition, for example, in the form of "release", when the number of the active substance is transformed into a bioavailable form, exceeds the amount of active substance that can be effectively processed by the target organ. Prematurely released active substance passes during this past target organ, not interacting with him. In therapeutic efficacy of the pharmaceutical composition can reduce the Xia.

Non-ionic hydrophilic polymers used in pharmaceutical compositions, which are selected from the group comprising hydroxyethyl cellulose (hereinafter SCE) with srednekamennogo molecular weight of 90000 to 1300000, preferably from about to about 1000000 1300000, hydroxypropylcellulose (hereinafter GPC) with srednekamennogo molecular weight of 370000 to 1,500,000, preferably from 850000 to 1,500,000, more preferably from 1200000 1000000 to, and polyethylene oxide (PEO) with srednekamennogo molecular weight of from 100000 to 500000, preferably from 150,000 to 300,000, more preferably 200000.

As examples of commercially available SCE-polymers can be called polymers manufactured by Hercules Incorporated, Aqualon Division, under the trademark NATROSOL® 250H or NATROSOL® 250L. As examples of commercially available MPC-polymers can be called polymers, which are also available from Hercules Incorporated. Aqualon Division, under the trademark KLUCEL® or KLUCEL® HXF, and as examples of commercially available PEO-polymers can be called polymers manufactured by Union Carbide Corporation under the trademark POLYOX®. Methods of obtaining non-ionic hydrophilic polymers suitable for use in the proposed in the invention compositions is well known to specialists in this field.

The content of non-ionic hydrophilic polymer in pharmaceutical is some of the composition may be from about 1 to about 20 wt.%, preferably from about 3 to about 12 wt.%, most preferably from about 4 to about 7 wt.%. Non-ionic hydrophilic polymer should be present in the pharmaceutical composition in a quantity sufficient to prevent premature release of pharmaceutically active substances.

As mentioned above, the pharmaceutical compositions according to the invention also contain HPMC in a quantity sufficient to provide slow release of the pharmaceutically active substance when it is received. The concept of "slow release" in the context of the present description means that the pharmaceutically active substance is released from the dosage form over an extended period of time, for example more than six hours. Preferably, during the first eight hours after administration of the pharmaceutical composition would be released approximately less than 80 wt.% the active substance is released from all of his number. In the preferred compositions for the first 0.5 hour after administration released approximately less than 15 wt.% pharmaceutically active substances, for about 2 hours after administration released from about 10 to about 50 wt.%, and for about 6 hours after administration released from about 40 to about 60 wt.% the pharmaceutical is if the active substance.

Content GPMC in the pharmaceutical compositions is from about 15 to about 50 wt.%, preferably from about 20 to about 40 wt.%, in terms of the total weight of the composition. The preferred mass ratio within the composition GPMC and non-ionic hydrophilic polymer is from about 10:1 to about 3:1, more preferably from about 7:1 to about 5:1 and most preferably about 6:1.

One of HPMC-polymers, which can be used in the proposed pharmaceutical composition is a polymer manufactured by Dow Chemical company under the trademark METHOCEL®. Preferably, in GPMC the degree of substitution by hydroxypropyl (SE) amounted to approximately 12, i.e. to the share of SOEs accounted for approximately 12% of the total number of functional groups in GPMC. Preferably, the SE content of functional groups in GPMC ranged from about 7 to about 12%, more preferably from about 7 to about 9%. The preferred viscosity values GPMC under normal conditions (2% HPMC in water) range from approximately 100 to approximately 100,000 CPS (at srednekamennogo molecular weight of from about 20,000 to about 170000. The most preferred SE the C is METHOCEL® K100LV with srednekamennogo molecular weight of from about 20,000 to about 30000. Methods of obtaining such GPMC-polymers are well known to specialists in this field.

After administration of the pharmaceutical composition non-ionic hydrophilic polymer and HPMC form a gel matrix in which the active substance. Pharmaceutically active substance is then gradually released from this gel matrix, resulting in slow release of the active substance, allowing a significant amount of the released active substance can efficiently interact with the target organ and recycled them. Gel matrix preferably should have sufficient stability to avoid significant premature destruction. The gel matrix must also be formed in such a period of time to effectively eliminate premature release of the active substance to its formation. For example, in order to avoid the "release" of the active substance to gel formation preferably, the gel matrix was formed within about 5 minutes after administration of the composition. I believe that non-ionic hydrophilic polymers reduces the rate of gel formation to an acceptable level.

As typical examples of pharmaceutically active among the STV, you can enter into the body with the use of the proposed invention in solutions include pharmaceutically active substance (but not limited to): (a) means acting on the Central nervous system (CNS), such as antipsychotics, anticonvulsants, including carbamazepine and oxcarbazepine, antidepressants, ANTIEPILEPTICS tools, tranquilizers and sleeping pills; b) means acting on the cardiovascular system, such as antiarrhythmic agent, reducing lipids in blood or tissue means antianginalnye tools, anticoagulants, antihypertensive, antiplatelet tools, diuretics and electrolytes (CA, K, Mg); C) anti-inflammatory agents, anti-asthma drugs, anti-arthritis funds reduce the glucose content in the blood means for oral administration and aromatase inhibitors.

For pharmaceutically active substances which can be entered through the provided compositions include organic and inorganic compounds, including (but not limited to) drugs acting on the peripheral nervous system, adrenergic receptors, cholinergic receptors, nervous system, skeletal muscles, cardiovascular system is the system, smooth muscles, the blood circulatory system, neuromuscular synapses, neuroeffector synapses, endocrine and hormonal system, immune system, reproductive system, skeletal system, digestive and excretory systems, inhibitors hormonal system and histamines systems, drugs acting on the Central nervous system, such as antidepressants, including amiflamine, amitriptyline, alaproclate, protriptyline, doxepin, imipramine, trazodon, Aprotinin, zimelidine, fluvoxamine, antipsychotic (neuroleptic) agents such as chlorpromazine, haloperidol, thioridazine, trifluoperazine, MK-0212, remoxipride, anti-convulsants such as carbamazepine oxcarbamazepine, phenytoin, phenobarbital, a sedative-hypnotics means, such as triazolam, chlordiazepoxide, temazepam, lorazepam, alprazolam, diazepam, flurazepam, lorazepam, oxazepam, and hydroxyzine, diazepam, meprobamate, butalbital, orphenadrine, chlorzoxazone, cyclobenzaprine, for the treatment of Parkinson's disease, such as benztropine, carbidopa, levodopa, L 647, 339, analgesics, such as acetaminophen, oxycodone, hydrocodone, codeine and propoksifen. Also may be used, acting on the respiratory system, including sympathomimetic agents, bronchodilators and antihistamines and asthma among the STV, as diethylpropion, ephedrine, epinephrine, isoproterenol, metaproterenol, terbutaline, cyproheptadine at, azatadine, diphenhydramine, promethazine, chlorpheniramine, brompheniramine, aminophylline. theophylline, albuterol, tranilast, enprofylline and budesonide. In addition, means can be used, acting on the cardiovascular system, and antihypertensives, including coronary vasodilator, cardiac glycosides, beta blockers, slow calcium channel blockers, antiarrhythmic agent, expanding peripheral vessels tools, such as the isosorbide dinitrate treatment, nitroglycerin, dipyridamole. digoxin, nadolol, propranolol, metoprolol, atenol, timolol, disopyramide, procainamide, nifedipine, quinidine, lidocaine, diltiazem, verapamil, prazosin, clonidin, hydralazine, hydrochlorothiazide methyldopa, captopril, metresin, enalapril, lisinopril, felodipine, tocainide. In addition, you can also use diuretics, such as amiloride, spironolactone, hydrochlorothiazide, chlorothiazide, acetazolamide, chlorthalidone, metolazone, furosemide, triamterene, methyclothiazide, ethacrynic acid, endocrine, antiatherosclerotic agents, such as conjugated estrogens, estradiol, ethinyl estradiol and diethylstilbestrol, progestins, such as progesterone, hydroxyprogesterone, medroxyprogesterone, norethindrone is, glucocorticoids and mineralcorticoids, such as hydrocortisone, betamethasone, dexamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone and MK-0621. In addition, can be used further non-steroidal anti-inflammatory drugs, anti-arthritis and protivopodagricakih tools, such as allopurinol, aspirin, fenoprofen, ibuprofen, indomethacin, naproxen, phenylbutazone, sulindac, tolmetin, diflunisal, piroxicam, meclofenamate, penicillamine, probenecid and colchicine, means acting on the gastrointestinal tract, including anticholinergic agents, antispasmodic remedies and anti-diarrhea and anti-ulcer antagonists histamine H2such as bethanechol, clidinium, dicyclomine, meclizine, prochlorperazine, trimethobenzamide, loperamide, cimetidine, ranitidine, Diphenoxylate, famotidine and omeprazole, oral agents to reduce the level of glucose in the blood, such as chlorpropamide, tolazamide and tolbutamide, anticoagulants, such as warfarin, phenindione and anisindione, disinfectant means, including antibiotics, antimicrobial agents, antiviral agents, protivodiabeticheskie tools and antifungal drugs, such as cefoxitin, thiabendazol, cephalexin, tetracycline, ampicillin, amoxicillin, sulfamethoxazole, cefaclor, erythromycin, pencil is in, nitrofurantoin, minocycline, doxycycline, cephalo-Smoking, miconazole, phenazopyridine, norfloxacin, clorsulon, flutolanil, pestiside, cilastin, phosphonomycin, ivermectin, imipenem, arprinocid and foscarnet, nutritional supplements, including vitamins, such as isotretinoin (vitamin a), vitamin D, tocopherol (vitamin E) and phytonadione (vitamin K), amino acids such as L-tryptophan and L-lysine, and lipids, such as corn oil and triglycerides medium chain length fatty acids. Another class of pharmaceuticals that can be used in the proposed compositions are tools that help to lower cholesterol levels in the body.

The content of the pharmaceutically active compounds of the above pharmaceutical compositions may comprise from about 0.1 to about 80 wt.%, preferably from about 10 to about 50 wt.%, more preferably from about 20 to about 40 wt.%.

To more effectively reduce cholesterol in the body is known to use in certain pharmaceutical compositions of the class of pharmaceutically active substances, known as inhibitors of HMG-CoA-reductase. Methods of obtaining inhibitors of HMG-CoA-reductase is well known to specialists in this field, and such tools include, for example, the R, such commercially available products, such as fluvastatin (manufactured by Novartis Pharmaceuticals, Inc., under the trademark LESCOL®), simvastatin (manufactured by Merck & Co., Inc., under the trademark ZOCOR®), atorvastatin (manufactured by Warner - Lambert under the trademark LIPITOR®), pravastatin (manufactured by Bristol-Myer Squibb under the brand name PRAVACHOL®), cerivastatin (manufactured by BASF under the trademark LIPOVAY®), lovastatin (manufactured by Merck & Co., Inc., under the brand name MEVACOR®) and mevastatin. Inhibitors of HMG-CoA reductase inhibitor can be used in the form of free acids, in the form of their esters or pharmaceutically acceptable salts. Such pharmaceutically acceptable salts include salts of sodium, calcium and salts of esters.

Inhibitors of HMG-CoA reductase inhibitor may be used as racemic mixtures or optionally in the form of more active stereoisomer. For example, you can use the racemic mixture of 3-R-5-S-fluvastatin sodium and 3-S-5-R-fluvastatin sodium, although it is found that the isomer 3-R-5-S-fluvastatin is more active.

Inhibitors of HMG-CoA reductase inhibitor may be present in an amount sufficient for inhibition of the biosynthesis of cholesterol in humans. In one embodiment, the content of such inhibitors HMG-CoA reductase inhibitor in the pharmaceutical composition may be from approx the flax 5 to about 50 wt.% in terms of the total weight of the composition. More preferable content of inhibitors of HMG-CoA reductase inhibitor in the composition is from about 20 to about 40 wt.% in terms of the total weight of the composition.

Other components that can be included in the composition to facilitate its processability and/or improve its properties are well known binders used in the manufacture of the tablets (such as gelatin, sugars, natural and synthetic gums, polyvinylpyrrolidone), disintegrating agents (such as crosscarmellose, crosspovidone, sodium salt starch glycolate), lubricants (such as magnesium stearate, hydrogenated vegetable oil, Carnauba wax), agents that increase the fluidity (such as silicon dioxide), agents for preventing adhesion, and lubrication (such as talc), as well as sweeteners, colorants such as iron oxide, aluminum in the form of flakes), fillers (such as lactose and other carbohydrates, pre-gelatinizing starch, sodium bicarbonate), flavouring agents and antioxidants. Specifically used for purposes other ingredients or their combination, and their number can be easily identified based on known standard procedures and on the basis of experience in the manufacture of a tablet, capsule or other dosage forms.

Example 1

Calculate the required mass of the portion of sodium salt of fluvastatin. Portions of sodium bicarbonate, microcrystalline cellulose, povidone, SMC and HPMC certain mass, placed in individually labeled containers. Then in the labeled container is placed also OPADRY® yellow, YS-1-6347-G, taken in 20%excess of the estimated quantity. Microcrystalline cellulose, sodium salt of fluvastatin, povidone, GOC and HPMC transferred in the order specified in the collet granulator (demand include Collette gral) and stirred for 5 minutes at low speed divider and switch off the shredder. The resulting mixture is sieved through a sieve with mesh size 0.033 inch using a vortex mill type "tornado"with blades facing in the direction of rotation, and running at low speed. The sifted material is then stirred into the collet granulator at low speed divider and switch off the shredder.

Sodium bicarbonate is dissolved in purified water to obtain a transparent homogeneous solution. Then a solution of sodium bicarbonate combined with the sifted material and the resulting mixture g is void in collet granulator at a high speed divider and a low speed shredder. After adding the above solution granulation continued for 30 seconds at high speed divider and a low speed shredder, and then for 30 seconds at high speed divider and a high speed grinder. The granulated mixture is then dried in a fluidized bed dryer at a temperature at the inlet 50°to a residual moisture content (LOD) 2-3 percent.

The dried granules are then sift through a sieve with mesh size 1/16 inch using a vortex mill type "tornado"with blades facing in the direction of rotation, and running at low speed. On the basis of the ratio between the amount of granular material, which was actually obtained by sieving through a sieve with mesh size of 1/16 inch, and theoretically calculated for this same stage a quantity of granulated material determine the amount of magnesium stearate. After this portion of stearate calculated mass of sieved through a sieve with a mesh size of 60 mesh and mixed with the dried granules in a free fall mixer, after which the resulting mixture is discharged in a bulleted drum with plastic inner lining. Further, from this granulated mixture through the extrusion is formed into tablets, which are then after removing dust and verification n the presence of metallic impurities stored in labeled plastic drum.

For coating tablets OPADRY® yellow mixed with purified water in an amount necessary to obtain a 10 wt.%-Noah suspension. The tablet is placed on a pallet for coating and heated to a temperature of 40-45°C. After that, the pill, spray applied coating of a suspension of OPADRY® yellow up until the coating weight will not reach 3% of the dry weight of the tablet. Then spray off and the tablet cool off the heated pan by shaking the last within 5 minutes.

Example 2

To obtain a dosage form containing a single dose, 84,24 mg of sodium salt of fluvastatin mixed in accordance with the procedure described in example 1 with the following ingredients shown in table 1.

Table 1
Sodium salt of fluvastatin84,24 mg
The potassium bicarbonate, USP8,42 mg
Microcrystalline cellulose, NF, PH101 (AVICEL®)111,26 mg
Povidone, USP4,88 mg
GOC, NF(KLUCEL® HXF)16,25 mg
GPMC, USP (METHOCEL®K 100LV)97,50 mg
Magnesium stearate2,44 mg
OPADRY® yellowof 9.75 mg

Example 3

To obtain a dosage form containing a single dose, 84,25 mg of sodium salt of fluvastatin mixed in accordance with the procedure described in example 1 with the following ingredients shown in table 2.

Table 2
Sodium salt of fluvastatin84,25 mg
The potassium bicarbonate, USP8,42 mg
Microcrystalline cellulose, NF, PH101 (AVICEL®)of 111.2 mg
Povidone, USP4,88 mg
GOC, HF(KLUCEL® HXF)16,25 mg
GPMC, USP (METHOCEL®K 100LV)32.50 to mg
GPMC, USP (METHOCEL®K15M)32.50 to mg
GPMC, USP (METHOCEL®KM)32.50 to mg
Magnesium stearate, NF2,44 mg
OPADRY® Yellow, YS-1-6347-Gof 9.75 mg

Example 4

To obtain a dosage form containing a single dose, 168,48 mg of sodium salt of fluvastatin mixed in accordance with the procedure described in example 1 with the following ingredients shown in table 3.

Table 3
Sodium salt of fluvastatin168,MH
The potassium bicarbonate, USP8,42 mg
Microcrystalline cellulose, NF, PH101 (AVICEL®)65,0 mg
Povidone, USP20,5 mg
GOC, NF(KLUCEL® HXF)20,5 mg
GPMC, USP (METHOCEL®K 100LV)to 110.7 mg
GPMC, USP (METHOCEL®)12,3 mg
Magnesium stearate, NF (1%)4,1 mg
OPADRY® red12,3 mg

Example 5

Of the pharmaceutical composition described in example 2 to prepare a number of dosage forms in which the mass percentage content GPMC speed was reduced to 30 wt.% up to 10 wt.% in increments of 5 wt.%. Then, for each of the dosage forms were determined by their solubility in water under stirring at a rotation speed of the blades of the stirrer at 50 rpm and a temperature of 37°C.

The results of each experiment are shown graphically in figure 1 where the solubility in percent is shown depending on the time.

Comparative example 1

In accordance with the procedure described in example 1 were prepared dosage form, the composition of which is given below in table 4.

Table 4
Sodium salt of fluvastatin42,12 mg
Sodium bicarbonate4,21 mg
Microcrystalline cellulose, NF (PH101)146,17 mg
Povidone6.25 mg
GOC, NF(KLUCEL® HXF)50,00 mg
Magnesium stearate NF1.25 mg
OPADRY® yellow10,00 mg

Comparative example 2

In accordance with the procedure described in example 1 were prepared dosage form, the composition of which is given below in table 5.

Table 5
Sodium salt of fluvastatin42,12 mg
Sodium bicarbonate4,21 mg
Microcrystalline cellulose, NF (PH101)118,67 mg
Povidone6.25 mg
GPMC, NF (METHOCEL® HXF)77,50 mg
Magnesium stearate1.25 mg
OPADRY® yellow10,00 mg

Comparative example 3

The dosage form of example 2, comparative example 1 and comparative example 2 were investigated on their solubility at a temperature of 37°placing each of them in 100 mm acetate buffer and stirring at a speed of rotation of the blades of the stirrer at 50 rpm

For the preparation of acetate buffet is and 4 grams of sodium hydroxide was dissolved in approximately 450 ml of water. the pH was brought to 4.0 by the addition of acetic acid and the solution was diluted with distilled water, bringing the volume up to one liter.

The obtained solubility data given in the graph in figure 2, which shows the dependence of the dissolution in the percent of the time. As shown in this drawing graphics, the composition of comparative example 1 containing fluvastatin MPC but not containing HPMC has undesirable high dissolution rate in comparison with the composition of example 2.

Comparative example 4

The dosage form of example 2, comparative example 1 and comparative example 2 were investigated on their solubility at a temperature of 37°placing each of them in 50 mm phosphate buffer with pH 6.8, and stirring at a speed of rotation of the blades of the mixer 50 and 100 rpm

For preparation of phosphate buffer 3,312 grams of nonoonono monohydrate of sodium phosphate and 3,692 grams dibasic anhydrous sodium phosphate was dissolved in approximately 500 ml of water. The resulting solution was diluted with distilled water, bringing the volume up to one liter.

The obtained solubility data given in the graph in figure 3, which shows the dependence of the dissolution in the percent of the time. As shown in this drawing, chart, profile release of the active substance to the composition is from example 2, containing fluvastatin, comparable with the stirring speed of 50 rpm with compositions containing fluvastatin and only GPMC or only the GOC.

Comparative example 5

The dosage form of example 2, comparative example 1 and comparative example 2 were investigated on their solubility at a temperature of 37°placing each of them in distilled water and stirring at a speed of rotation of the blades of the stirrer at 50 rpm

The obtained solubility data for each dosage form is shown in the graph in figure 4, which shows the dependence of the dissolution in the percent of the time. As shown in this drawing, chart, profile release of the active substance for the composition of example 2 containing fluvastatin compared with compositions containing fluvastatin and only GPMC or only the GOC.

Comparative example 6

The dosage form of example 2 and comparative example 2 re-examined on their solubility at a temperature of 37°placing each of them in 50 mm phosphate buffer with pH 6.8, and stirring at a speed of rotation of the blades of the stirrer at 50 rpm

For preparation of phosphate buffer 3,312 grams of nonoonono monohydrate of sodium phosphate and 3,692 grams dibasic anhydrous sodium phosphate was dissolved in approximately 500 ml of water. The resulting solution was diluted with di is fillerbunny water, bringing the volume up to one liter.

The obtained solubility data for formulations of example 2 and comparative example 2 are shown in the graphs in figure 5 and 6 respectively, showing the dependence of the dissolution in the percent of the time. As follows from the comparison shown in figure 5 and 6 charts, reproducible results that characterize the dissolution profile for the composition of example 2 containing and HPMC, and the GOC, higher than for the composition of comparative example 2 containing only HPMC.

1. Pharmaceutical composition with delayed release, to avoid the effect of "release"containing fluvastatin or its pharmaceutically acceptable salt, hypromellose and non-ionic hydrophilic polymer selected from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of 90000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 370000 to 1,500,000 and polyethylene oxide with srednekamennogo molecular weight of from 100000 to 500000.

2. The pharmaceutical composition according to claim 1, in which the non-ionic hydrophilic polymer selected from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of from 1000000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 850000 to 1,500,000, and poly is telenokia with srednekamennogo molecular weight of from 150,000 to 300,000.

3. The pharmaceutical composition according to claim 1, in which the non-ionic hydrophilic polymer is hydroxypropylcellulose with srednekamennogo molecular weight of about 1150000.

4. The pharmaceutical composition according to claim 1, containing from about 5 to about 50 wt.% of fluvastatin or its pharmaceutically acceptable salt, calculated on the total weight of the composition.

5. The pharmaceutical composition according to claim 1, containing from about 20 to about 40 wt.% of fluvastatin or its pharmaceutically acceptable salt, calculated on the total weight of the composition.

6. The pharmaceutical composition according to claim 1, containing from about 15 to about 50 wt.% specified hydroxypropylmethylcellulose in terms of the total weight of the composition.

7. The pharmaceutical composition according to claim 1, containing from about 20 to about 40 wt.% specified hydroxypropylmethylcellulose in terms of the total weight of the composition.

8. The pharmaceutical composition according to claim 1, containing from about 3 to about 12 wt.% specified non-ionic hydrophilic polymer, calculated on the total weight of the composition.

9. The pharmaceutical composition according to claim 1, containing from about 4 to about 7 wt.% specified non-ionic hydrophilic polymer, calculated on the total weight of the composition.

10. Pharmaceutical companies who stand according to claim 1, in which the mass ratio between the specified hypromellose and specified non-ionic hydrophilic polymer is from about 10:1 to about 3:1.

11. The pharmaceutical composition according to claim 1, in which the mass ratio between the specified hypromellose and specified non-ionic hydrophilic polymer is from about 7:1 to about 5:1.

12. The method of release of fluvastatin in the body of a mammal, comprising oral administration of fluvastatin to the mammal in a pharmaceutical composition comprising fluvastatin or its pharmaceutically acceptable salt, hypromellose and non-ionic hydrophilic polymer selected from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of 90000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 370000 to 1,500,000 and polyethylene oxide with srednekamennogo molecular weight of from 100000 to 500000.

13. The method according to item 12, where the non-ionic hydrophilic polymer is chosen from the group comprising hydroxyethyl cellulose with srednekamennogo molecular weight of from 1000000 to 1300000, hydroxypropylcellulose with srednekamennogo molecular weight of 850000 to 1,500,000 and polyethylene oxide with srednekamennogo molecular weight of from 150,000 to 300,000.

14. The method according to item 12, where it is config hydrophilic polymer is hydroxypropylcellulose with srednekamennogo molecular weight of about 1150000.

15. The method according to item 12, where the pharmaceutical composition contains from about 5 to about 50 wt.% of fluvastatin or its pharmaceutically acceptable salt, calculated on the total weight of the composition.

16. The method according to item 12, where the pharmaceutical composition comprises from about 15 to about 50 wt.% specified hydroxypropylmethylcellulose in terms of the total weight of the specified composition.

17. The method according to item 12, where the pharmaceutical composition contains from about 3 to about 12 wt.% specified non-ionic hydrophilic polymer, calculated on the total weight of the specified composition.

18. The pharmaceutical composition according to claims 1 to 11, in which the degree of substitution by hydroxypropyl in the hypromellose is approximately 7 to 9% of hydroxypropyl.

19. The pharmaceutical composition according p containing 84,24 mg of sodium salt of fluvastatin, 8,42 mg of potassium bicarbonate, of 11.26 mg microcrystalline cellulose, NF, PH101, AVICEL®, 4,88 mg povidone, 16,25 mg hydroxypropylcellulose NF, KLUGEL®HXF, 97,50 mg hydroxypropylmethylcellulose METHOCEL®To 100LV, 2,44 mg stearate and 9.75 mg coating OPADRY®yellow.

20. The pharmaceutical composition according p containing 84,25 mg of sodium salt of fluvastatin, 8,42 mg of potassium bicarbonate, 111,2 mg microcrystalline cellulose, NF, PH101, AVICEL® , 4,88 mg povidone, 16,25 mg hydroxypropylcellulose NF, KLUGEL®HXF, 32.50 to mg hydroxypropylmethylcellulose METHOCEL®To 100LV, 32.50 to mg hydroxypropylmethylcellulose METHOCEL®To 15M, 32.50 to mg hydroxypropylmethylcellulose METHOCEL®To 4M, 2,44 mg of magnesium stearate, NF, and 9.75 mg coating OPADRY®yellow, YS-1-6347-G.

21. The pharmaceutical composition according p containing 168,48 mg of sodium salt of fluvastatin, 8,42 mg of potassium bicarbonate, 65 mg of microcrystalline cellulose, NF, PH101, AVICEL®, 20,5 mg povidone, 20,5 mg hydroxypropylcellulose NF, KLUGEL®HXF, to 110.7 mg hydroxypropylmethylcellulose METHOCEL®To 100LV, 12,3 mg hydroxypropylmethylcellulose METHOCEL®, 4,1 mg of magnesium stearate, NF(1%), and 12.3 mg coating OPADRY®red.

22. The pharmaceutical composition according to claims 1-11, designed to produce medicines to lower cholesterol in plasma.



 

Same patents:

FIELD: medicine.

SUBSTANCE: means has lipid fraction obtained from Berryteuthis Magister Comandor squid liver containing 10% of polyunsaturated fatty acids and 50% of alkyl-diacylglycerides showing marked lipid-correcting and immunomodulating properties.

EFFECT: enhanced effectiveness in treating lipid metabolism disorders and immunity system disorders.

4 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a prophylactic or therapeutic agent used against hyperlipidemia and comprising as an active component the heterocyclic compound of the formula [1]:

or its pharmaceutically acceptable salt wherein R1 represents aryl optionally substituted with similar or different one-three groups taken among alkyl, halogenalkyl, trihalogen alkyl, alkoxy-group and halogen atom; Het represents bivalent aromatic heterocyclic group of the formula [5]:

wherein X represents oxygen, sulfur atom or NR6 wherein R6 represents hydrogen atom or alkyl; R2 represents hydrogen atom, alkyl or trihalogenalkyl; D represents alkylene and alkenylene; E represents group of the formulae [3] or [4] wherein Y represents oxygen or sulfur atom; R3 and R4 are similar or different and each represents hydrogen atom or alkyl; p = 1; Z represents carboxy-group, alkoxycarbonyl, cyano-group or 1H-5-tetrazolyl. Also, invention relates to new compounds belonging to group of above enumerated heterocyclic compounds of the formula [1] that show effect reducing blood triglycerides level, low density lipoprotein cholesterol, glucose and insulin or effect enhancing high density lipoprotein cholesterol and effect reducing the atherogenic effect. Therefore, these compounds can be used in prophylaxis or treatment of hyperlipidemia, arteriosclerosis, heart ischemic disease, brain infarction, rheocclusion after percutaneous intraluminal coronary angioplasty, diabetes mellitus and obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

29 cl, 1 tbl, 170 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to methods for treatment of diseases or syndromes associated with metabolism of fatty acids and glucose and to new compounds and their pharmaceutically acceptable salts. Invention relates to applying new compounds and pharmaceutical compositions for treatment of cardiovascular diseases, diabetes mellitus, cancer diseases, acidosis and obesity by inhibition of activity of enzyme malonyl-CoA-decarboxylase. Indicated compounds correspond to formulae (I) and (II) wherein Y, C, R1, R2, R6 and R7 have values given in the invention claim.

EFFECT: valuable medicinal and biochemical properties of azoles.

27 cl, 8 tbl

FIELD: biopharmacology, medicine.

SUBSTANCE: the suggested biotransplant contains an active component: the culture of genetically unmodified neuronal stem cells (NSC) obtained out of anterior cerebral tissue of human embryos of the 1st trimester of pregnancy or periventricular cerebral area of 15-20 wk gestation and selectively multiplied under cultivating conditions up to the quantity of 10 (7) - 10 (9) pluripotent undifferentiated cells in composition of neurospheres, at the content of NSC being 50-500 mln., and 2 ml physiological solution. The method for treating ischemic insult deals with introduction of 50-500 mln. NSC in 2 ml physiological solution. The suggested biotransplant and method for treating ischemic insult enable to quickly restore and improve cerebral functions.

EFFECT: shortened terms of therapy.

5 cl, 2 ex, 1 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted 1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines of the general formula (1)

that are effective inhibitors if caspase-3 that can be used for preparing medicinal agents and for experimental (in vitro, in vivo) investigation of apoptosis processes as "pharmacological tools". Also, invention proposes pharmaceutical composition and a method for their preparing and applying. In the general formula (1) radicals R1, R2, R3 and R8 represent independently of one another hydrogen atom, halogen atom, CF3, CN, inert substitute, optionally substituted hydroxyl group, optionally substituted carboxy-(C1-C6)-alkyl group, optionally substituted carbamoyl group; R4 represents hydrogen atom, halogen atom, inert substitute, optionally substituted amino-group, substituted hydroxyl group; R5 represents hydrogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; R6 and R7 represent independently of one another hydrogen atom, inert substitute, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; or R6 and R7 in common with nitrogen atom to which they are bound represent optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur, 3-10-membered cycle; or R6 and R7 in common with nitrogen atom to which they are bound represent condensed heterocycle being optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur.

EFFECT: improved preparing method and treatment.

9 cl, 19 sch, 7 tbl, 25 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes diazepane derivative of the general formula (I)

or its pharmaceutically acceptable salt wherein ring B means phenyl; ring A means pyridyl substituted with halogen atom optionally, or phenyl substituted optionally with lower alkyl, lower alkoxy-group or halogen atom; X1 represents -C(=O)-NR2- or -NR2-C(=O)- wherein R2 means hydrogen atom; X2 represents -C(=O)-NR3- or NR3-C(=O)- wherein R3 means hydrogen atom; R represents hydrogen atom or halogen atom; R1 means lower alkyl. Also, invention relates to a pharmaceutical composition and inhibitor of blood coagulation activated factor X that can be used for prophylaxis and treatment of patients suffering with thrombosis or embolism.

EFFECT: valuable medicinal properties of compound.

5 cl, 5 tbl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes applying the known 2-imidazolyl-substituted carbinols as inhibitor of Na+/H+ exchange in treatment or prophylaxis of diseases caused by ischemia (myocardium infarction, stenocardia, heart ischemic state, ischemic state of peripheral and central nervous system, insult, shock state, hypoxic states of donor organs in removing, storage and transplantation in the recipient body). Also, compounds can be used as anti-arrhythmic agents with cardioprotective effect and for prophylaxis of high blood pressure genesis in essential hypertension.

EFFECT: valuable medicinal properties of compounds.

10 cl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of tetrahydroisoquinoline of the formula [I] wherein R1 represents hydrogen atom or lower alkyl; R2 represents alkyl having optionally a substitute taken among alkoxycarbonyl and carboxy-group, cycloalkyl, cycloalkylalkyl, aryl having optionally a substitute taken among lower alkyl, arylalkyl having optionally a substitute taken among lower alkyl, lower alkoxy-group, halogen atom and acyl, alkenyl, alkynyl, or monocyclic heterocyclylalkyl wherein indicated heterocycle comprises 5- or 6-membered ring comprising nitrogen atom and having optionally a substitute taken among lower alkyl; R3 represents hydrogen atom or lower alkoxy-group; A represents a direct bond or >N-R5 wherein R5 represents lower alkyl; B represents lower alkylene; Y represents aryl or monocyclic or condensed heterocyclyl comprising at least one heteroatom taken among oxygen atom and nitrogen atom and having optionally a substitute taken among lower alkyl, carboxy-group, aryl, alkenyl, cycloalkyl and thienyl, or to its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition eliciting hypoglycaemic and hypolipidemic effect based on these derivatives. Invention provides preparing new compounds and pharmaceutical agents based on thereof, namely, hypoglycaemic agent, hypolipidemic agent, an agent enhancing resistance to insulin, therapeutic agent used for treatment of diabetes mellitus, therapeutic agent against diabetic complication, agent enhancing the tolerance to glucose, agent against atherosclerosis, agent against obesity, an anti-inflammatory agent, agent for prophylaxis and treatment of PPAR-mediated diseases and agent used for prophylaxis and treatment of X-syndrome.

EFFECT: valuable medicinal properties of compounds and composition.

13 cl, 7 tbl, 75 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compound of the formula (I) or its pharmaceutically acceptable salt or solvate wherein X represents CH or nitrogen atom (N); Z represents CH; R1 represents hydrogen atom; R2 and R3 can be similar or different and represent (C1-C6)-alkoxy-group that is optionally substituted with halogen atom, hydroxyl, (C1-C4)-alkoxycarbonyl, amino-group wherein one or two hydrogen atom are optionally replaced for (C1-C4)-alkyl that is optionally substituted with hydroxyl or (C1-C4)-alkoxy-group, the group R12R13N-C(=O)-O- wherein R12 and R13 can be similar or different and represent hydrogen atom or (C1-C4)-alkyl substituted optionally with (C1-C4)-alkoxy-group or the group R14-(S)m- wherein R14 represents phenyl or saturated or unsaturated 5-7-membered heterocyclic group substituted optionally with (C1-C4)-alkyl; m = 0 or 1; R4 represents hydrogen atom; R5, R6, R7 and R8 can be similar or different and represent hydrogen atom, halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy-group or nitro-group under condition that R5, R6, R7 and R don't represent hydrogen atom simultaneously; R9 represents hydrogen atom, (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl wherein alkyl fragment of indicated (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl is optionally substituted with (C1-C4)-alkoxy-group; R10 represents hydrogen atom or (C1-C6)-alkyl; R11 represents (C1-C6)-alkyl, (C2-C6)-alkenyl or (C2-C6)-alkynyl (wherein each (C1-C6)-alkyl, (C2-C6)-alkenyl and (C2-C6)-alkynyl is substituted optionally with halogen atom or (C1-C6)-alkoxy-group), or R15-(CH2)n- wherein n is a whole number from 0 to 3; R15 represents naphthyl or 6-membered saturated or unsaturated carbocyclic or saturated or unsaturated 5-7-membered heterocyclic group that are substituted optionally with halogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group. Also, invention relates to variants of compounds of the formula (I). Compounds elicit antitumor activity and don't effect on cytomorphosis. Also, invention relates to pharmaceutical composition based on above described compounds, to a method for treatment of such diseases as malignant tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, Kaposi's sarcoma, and to a method for inhibition of vascular vessels angiogenesis.

EFFECT: valuable medicinal properties of compounds and composition.

22 cl, 4 tbl, 186 ex

FIELD: pharmaceutical industry.

SUBSTANCE: invention discloses solid oral dozed pharmaceutical form of hydrocodon with controlled release. Pharmaceutical form comprises analgetically effective amount of hydrocodon or pharmaceutically acceptable salt thereof and controlled-release material. Pharmaceutical forms of hydrocodon are suitable to be administered once a day and provides early commencement of therapeutical effect, which lasts at least about 24 h.

EFFECT: enhanced analgetic action.

44 cl, 3 tbl, 3 ex

FIELD: pharmaceutics, medicine.

SUBSTANCE: the present innovation deals with cardiotherapy for treating and preventing coronary deficiency. The preparation is designed as a plate (film) consisted of three layers, each of them is manufactured out of co-polymer of vinyl pyrrolidone, acrylamide and nitroglycerin-containing ethylacrylate; moreover, internal layer additionally contains solid fat - cacao oil, and weight ratio for the sum of external layers to internal corresponds to 1 : 1. The suggested preparation could additionally contain brilliant green dyestuff. The preparation should be manufactured out of pre-obtained mixture of nitroglycerin and copolymer in solution of alcohol and water followed by layer-by-layer forming three-layer film due to spreading the mixture onto solid bottom plate and drying at 30-50 C. The innovation provides higher adhesion to gingival mucosal surface, decreased side action, improved bioavailability and stability of therapeutic effect.

EFFECT: higher efficiency of therapy.

3 cl, 3 ex

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to human insulin drug of durable action. Drug contains human insulin substance of high purity, protamine sulfate, zinc chloride, glycerol, m-cresol, phenol, sodium dihydrogenphosphate dihydrate or disodium hydrogenphosphate heptahydrate, sodium chloride, and water and has residual proteolysis activity not more than 0.005 adsorption units.

EFFECT: human insulin drug of durable action with increased physiological activity and physical and chemical storage stability.

4 ex, 1 tbl

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to human insulin drug with activity of 100 IU/ml, including cartridge forms. Drug contains active ingredient, glycerol as isotonic agent, conserving agent and water, wherein it contains human insulin substance of high purity with residual proteolysis activity not more than 0.005 adsorption units, sodium chloride as additional isotonic agent, m-cresol as conserving agent, and additionally sodium dihydrogenphosphate dihydrate or disodium hydrogenphosphate heptahydrate as substance with buffer capacity and pH 6.9-7.8.

EFFECT: human insulin drug of short action with increased physiological activity and physical and chemical storage stability.

6 ex, 1 tbl

FIELD: pharmaceutics.

SUBSTANCE: the present innovation deals with pharmaceutical composition of bactericidal action. The composition suggested contains ciprofloxacin in the form of hydrochloride monohydrate, maltodextrin as a binding substance, sodium carboxymethyl starch as a disintegrating agent, silica gel, a lubricant at quantities mentioned in its formula. Ciprofloxacin tablets should be obtained due to pressing technique by applying the stage of moisture granulation. If necessary, the surface of tablets should be covered with a hydroxypropylmethylcellulose-based water-soluble membrane. Simultaneous application of maltodextrin as a binding substance and sodium carboxymethyl starch as a disintegrating agent enables to obtain ciprofloxacin-containing tablets of sufficient strength and quick release of active ingredient.

EFFECT: higher efficiency of application.

6 cl, 6 ex, 9 tbl

FIELD: pharmaceutical industry.

SUBSTANCE: invention provides oral-administration beta-histin-based controlled-release solid preparation prepared by granulating active ingredient from melt with fat component added followed by mixing thus obtained granulate with hydrophilic polymer and conventional excipients. Invention enables preparation of pharmaceutical dosage form with appropriate beta-histin release profile allowing reduction of daily drug intake to single dose, whereas concentration of active ingredient is kept constant within therapeutical dose limits.

EFFECT: facilitated therapeutical treatment.

4 cl, 14 ex

FIELD: medicine, cardiology, pharmacy.

SUBSTANCE: invention relates to carvedilol-containing pharmaceutical composition that is used for treatment and/or prophylaxis of hypertension, cardiac insufficiency or stenocardia. The composition comprises carvedilol or its pharmaceutically acceptable salt and one or some adjuvants. Carvedilol is distributed in adjuvants as a molecular dispersion. Adjuvants are not surface-active substance and/or non-ionogenic surface-active substance. The concentration of adjuvants exceeds 5 wt.-%. Also, invention describes a method for preparing the composition and pharmaceutically acceptable solid formulation for oral administration. Compositions of the present invention provide the enhancing solubility of carvedilol and level of its absorption in lower regions of intestine.

EFFECT: improved and valuable pharmaceutical properties of composition.

17 cl, 9 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a medicinal formulation with the constant rate for releasing a medicinal substance, core of medicinal formulation and to a method for providing relieved release of medicinal substance. Medicinal formulation comprises medicinal substance-containing layer and semi-permeable wall and expanding layer. A layer promoting to moving forward is placed between semi-permeable wall and medicinal substance-containing layer and the content of medicinal substance is at least 20% of the total layer mass containing a medicinal substance. Invention provides releasing practically all amount of medicinal substance from medicinal formulation to medium for it applying.

EFFECT: improved and valuable medicinal and pharmaceutical properties of medicinal formulation.

12 cl, 13 dwg, 8 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition that comprises internal lipophilic matrix and external hydrophilic matrix in the mass ratio of lipophilic and hydrophilic matrices from 100:0.5 to 100:20. The internal lipophilic matrix consists of substances with melting point below 90oC and comprises at least partially an active component as globules. As an active component the composition comprises mesalazine - 5-aminosalicylic acid in the concentration up to 95 wt.-%. Lipophilic matrix is dispersed in external hydrophilic matrix. The composition can comprise optionally other excipients. Also, invention describes a method for preparing the composition. Invention provides sustained-release of mesalazine from first phases after administration and more homogenous pattern of release as compared with conventional systems.

EFFECT: improved properties of composition.

11 cl, 5 ex

FIELD: medicine, in particular composition for quick-disposable in buccal cavern tablets.

SUBSTANCE: claimed composition contains granulated product of fine dispersed long releasing particles, comprising drug and fillers selected from group including sugars and sugar alcohols together with binder, wherein content of non-granulated fine dispersed long releasing particles is 0-15 %. Method for production of such tablets is also disclosed.

EFFECT: pharmaceutical composition with accelerated degradation.

24 cl, 9 ex, 3 dwg

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to peroral immediate-released drug in solid form, containing low molecular thrombin inhibitor based on peptide with pH-depending solubility. Claimed drug has size particle less than 300 mum and contains combination of microcrystal cellulose and sodium glycolate starch in amount of more than 35 mass % (calculates as preparation mass).

EFFECT: drug with reduced dependence of thrombin inhibitor dissolution from pH and increased releasing rate from tablet.

17 cl, 3 ex, 3 dwg

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