UA81279C2 - Pharmaceutical dosage form - Google Patents

Abstract

The invention relates to medicine, in particular to pharmacy, and is intended for administering medicinal preparations and use them as hygiene remedy. A pharmaceutical dosage form has a form of a capsule filled with pharmaceutically active ingredient in liguid or jellylike state. The capsule cover is made of elastic polymer insoluble in water, saliva and digestive juice such as liquid rubber, rubber or polyurethane and has stress concentrators.

Description

Description of the invention

The invention relates to medicine, pharmacology and pharmacotherapy, in particular, it is intended to ensure 2 administration of medicinal products and use as a means of hygiene.

The known method of manufacturing the dosage form is described in the international application MoUUO 00/13663 published on 16.03.2000, IPC 7 Ab1KOU/22, and in the Russian Federation the application was published on 20.01.2003 under

Mo2001107030Y. The essence is that an osmotic hydrogel and an osmotic effective solute are mixed to obtain a composition that expands in volume in the presence of an aqueous liquid, 70 tihydroxyalkyl cellulose and water are mixed to obtain a granulation solution, the composition that expands in volume is sprayed with a granulation solution, with by obtaining granules, then mix a medicinal substance, a surface-active substance and a component selected from the group that includes mono- and diglyceride with obtaining a composition of a medicinal substance and introduce the composition of the medicinal substance into a capsule, then sprinkle granules of the composition are introduced into the capsule, cover the capsule with a semi-permeable composition with the formation of a membrane that 79 contains cellulose acetate and polyethylene glycol or a composition of a thermoplastic polymer having a softening temperature of 40-180 C, permeable to an aqueous liquid, and an exit hole is made in the obtained membrane for the delivery of the medicinal substance from the obtained dosage form with delayed release and control at a constant rate for a long time. Moreover, first a solution for granulation is obtained, and then a composition that expands in volume in the presence of an aqueous liquid is obtained, first the sprayed composition is introduced into the capsule, and then the composition of the medicinal substance. The composition of the medicinal substance contains polyoxyl C5 castor oil and acegylated monoglyceride.

To obtain a composition of a medicinal substance, a medicinal substance containing a component selected from the group consisting of a peptide, protein, protein anabolic hormone, growth-stimulating hormone, hormone of the endocrine system, porcine growth-stimulating hormone, bovine growth-stimulating hormone, c 29 equine growth-stimulating hormone, human growth-stimulating hormone, hormone isolated from the pituitary gland, (U hormone isolated from the hypothalamus, recombinant DNA, somatotropin, gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, and H-KN (luteinizing hormone-releasing hormone), insulin, colchicine, chorionic gonadotropin, oxytocin, vasopressin, desmopressin, adrenocorticotropic hormone, prolactin, bipressin, thyroid-stimulating hormone, secretin, pancreozymin, enkephalin and F 30 glucagon. -

The composition of the medicinal substance includes a two-phase emulsion and contains an agent that contributes to the emulsification of the composition of the medicinal substance, which includes a component selected from the group consisting of polyoxyethylenated castor oil containing 9-52 mol of ethylene oxide, polyoxyethylenated sorbitan monopalmitate containing 2Omol of ethylene oxide, of polyoxyethylenated sorbitan monostearate containing 20 mol

From ethylene oxide, polyoxyethylenated sorbitan monostearate containing 4 mol of ethylene oxide, from polyoxyethylenated sorbitan tristearate containing 20 mol of ethylene oxide, polyoxyethylenated sorbitan trioleate containing 20 mol of ethylene oxide, polyoxyethylenated stearic acid containing 1 mol of ethylene oxide, polyoxyethylenated ether, polyoxyethylenated stearic acid containing 40-50 mol ethylene oxide, polyoxyethylenated stearic acid containing 5Omol of ethylene oxide, C7Z polyoxyethylenated stearyl alcohol containing 2mol of ethylene oxide, and polyoxyethylenated c oleyl alcohol containing 2mol of ethylene oxide. "with the composition of the medicinal substance is an emulsified composition containing a component selected from the group consisting of oil of vegetable, mineral, animal or marine origin, ester of an unsaturated fatty acid, monoglyceride, diglyceride, triglyceride, acetylated glyceride, olein, palmitin, stearin, hexyl ester of lauric acid, oleic acid, oleyl ester, glycolized ethoxylated glycerides of oils, fatty acids containing 13 molecules of ethylene dioxide and - decyl ester of oleic acid.

Common essential features are that the controlled-release pharmaceutical dosage form with variable release rates includes a polymer shell and one or more pharmaceutical-I 250 active ingredients.

The disadvantages of the known technical solution are that the release rate is set during manufacture and c cannot be changed by the patient himself when taking it, there is a need to introduce thickeners or a soluble edible coating into the drug that enters the stomach, the difficulty of ensuring uniform distribution of the drug throughout the oral cavity , as well as the absence of pleasant tactile sensations during reception. 99 The closest in essence is the pharmaceutical dosage form described in the international application MO 03/00791

GF) dated January 30, 2003, which was published in the Russian Federation on March 10, 2005 under Mo 2004104950, class IPK7 AbETDO9/Z6I. A pharmaceutical dosage form with controlled release and variable release rates, includes: 1) a two-layer or multi-layer tablet core, in which at least one of the layers contains one or more 60 pharmaceutical active ingredients, and at least one of the layers contains one or more rate-regulating polymers; 2) strictly speaking, an insoluble shell located on top of the tablet core, which covers a large part of the tablet surface, but leaves part of one layer of the tablet open (open layer), and this shell is obtained as a result of electrostatic deposition of powder containing fusible particles onto the core because tablets and melting of these particles to form a thin film. A dosage form having increased release rates during a defined period of time, in which the open layer contains a smaller amount of the active substance and/or has a lower release rate than the other (closed) layer, which also releases the active ingredient during the first period at a lower rate than during the following second period.

At least one layer of the tablet core contains a binder selected from gum arabic, alginic acid, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, dextrin, ethylcellulose, gelatin, glucose, guar gum, hydrogenated vegetable oil, hydroxypropylmethylcellulose, magnesium aluminum silicate, maltodextrin, methylcellulose, polyethylene oxide, povidone, sodium alginate and hydrogenated vegetable oils.

At least one layer of the tablet core further contains a diluent selected from lactose, cellulose, 70 dicalcium phosphate, sucrose, dextrose, fructose, xylitol, mannitol, sorbitol, calcium sulfate, starches, calcium carbonate, sodium carbonate, dextrates, dextrin, kaolin, lactitol, magnesium carbonate, magnesium oxide, maltitol, maltodextrin and maltose.

Moreover, the shell contains a polymer resin selected from polymethacrylates, cellulose and its derivatives, simple and complex cellulose esters and cellulose acetate phthalate. The shell contains a plasticizer selected from /5 Polyethylene glycol, triethyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, tributyl citrate, diethyl phthalate, dibutyl phthalate, dimethyl phthalate, dibugyl sibacenate, and glyceryl monostearate. The shell has an average thickness of 20 to 50 μm and gives an increase in mass less than 5 95 of the mass of the core of the tablet. The active ingredient is selected from agents affecting gastric acidity and peristalsis, laxatives, antidiarrheal agents, colorectal agents, pancreatic enzymes and bile acids, antiarrhythmic agents, antianginal agents, diuretics, antihypertensive agents, anticoagulants, antithrombotic agents, fibrinolytic agents, hemostatic agents, hypolipidemic agents, anti-anemia agents and neurotropic agents, hypnotic agents, anxiolytics, antipsychotic agents, antidepressants, antiemetic agents, anticonvulsants, CNS stimulants, analgesics, antipyretic agents, anti-migraine agents, non-steroidal anti-inflammatory agents, anti-gout agents, m' ulcer relaxants, neuromuscular agents, steroids, hypoglycemic agents, hyperglycemic agents, diagnostic agents, antibiotics, antifungal agents, antimalarial agents, antiviral agents, immunosuppressants, nutritional i) agents, vitamins, electrolytes , anorectic agents, appetite suppressants, bronchodilators, expectorants, antitussives, mucolytic agents, anti-edema agents, anti-glaucoma agents, oral contraceptives, diagnostic and neoplastic agents. General essential features are that a pharmaceutical dosage form with controlled release and variable release rates includes a polymer shell and one or more pharmaceutical active ingredients. with

The disadvantages of the known technical solution are that the release rate is set during manufacture and cannot be changed by the patient himself during administration, as well as the fact that it is necessary to introduce into the drug "7 zv Thickeners or a soluble, relatively edible, shell that enters the stomach, the difficulty of providing uniform distribution of the drug throughout the oral cavity, as well as the absence of pleasant tactile sensations when taking it.

The purpose of the invention is to create a pharmaceutical dosage form in the form of a capsule, to ensure oral administration of medicinal substances in liquid or gel-like form without additional ingredients, with "providing a variable rate of release regulated by the patient himself, including ensuring the psychological situation of taking medicinal substances from creating pleasant tactile sensations and ensuring complete irrigation of the oral cavity with the medicinal product. ;" To realize the set goal. A pharmaceutical dosage form with controlled release and variable release rates, includes a shell and one or more pharmaceutical active ingredients. The pharmaceutical active ingredient is in a liquid or jelly-like state, in a sealed container

Go! an elastic capsule made of a polymer insoluble in water, saliva and gastric juice with a shell that has stress concentrators, for the possibility of reducing the load necessary to break the tightness by the load from human teeth, in order to ensure the possibility of the active ingredient flowing out under the load into the oral cavity depending on the speed and forces of masticatory movements. Stress concentrators are made in the form of conical depressions in the shell of the capsule, undercuts or other local reductions in wall thickness. The shell of the capsule is made of an elastic elastic material of latex, polyurethane or rubber and has an average thickness of more

Ge) parts of the area in the range of 0.5-2.5 mm or a capsule with an elastic inelastic shell with an average thickness of 0.1-0.5 mm is filled with elastic porous material or elastic twisted monofilaments and is filled with a pharmaceutical active ingredient no more than 90 95. The shell of the capsule can have a spherical shape or an ellipsoid or an ovoid and, on one of the ends, has a thickening of the wall that exceeds by 2-4 times the main thickness of the shell, on one of the ends there is a hole, which is closed with a stopper made of polymer material. Capsule shell

F) can also have a shape close to a cylindrical one and is made of a polymer tube separated by transverse or double thermal seams at equal intervals into separate capsules. Also, the capsule shell can have the shape of a "cushion". In all cases, the distinctive essential features are that the pharmaceutical active ingredient in a liquid or gel-like state is in a hermetic elastic capsule made of a polymer insoluble in water, saliva and gastric juice shell, which has voltage concentrators.

The signs that are significant in some cases are: - that the voltage concentrators in the number of at least one are made in the form of conical recesses in the shell 65 of the Capsule; - that the shell of the capsule is made of an elastic elastic material, for example latex, polyurethane or rubber and has an average thickness of 0.5-2.5 mm over the main area; - that the capsule with an elastic polymer shell is filled with elastic porous material or elastic twisted monofilaments and is filled with the pharmaceutical active ingredient by no more than 90 95, has

Local thickening of the wall of the shell in which the hole is closed with a plug made of polymer material; - that the shell of the capsule has a spherical shape, for example, an ellipsoid of rotation or an ovoid, and has a local thickening of the wall that is 2-4 times greater than the main thickness of the wall of the shell; - that the shell has a cylindrical shape and is made of a polymer tube, the cavity of which is divided by transverse double thermal seams at equal intervals into separate capsules connected to each other by the wall 70 of the shell; - that the capsule shell has the shape of a "cushion".

Figure 1 shows a pharmaceutical dosage form in the form of a capsule with an elastic elastic shell;

Fig. 2 shows the section AA;

Figure 3 shows a pharmaceutical dosage form with an elastic inelastic shell;

Fig. 4 shows the B-B section;

Figure 5 shows a pharmaceutical dosage form when made from a tube;

Fig. 6 shows the section B-B;

Figure 7 shows a pharmaceutical dosage form with capsules in the form of a "cushion";

Fig. 8 shows the section GG.

The pharmaceutical dosage form is a hermetic elastic capsule made of a polymer shell insoluble in water, saliva and gastric juice, having any shape and size convenient from a technological and consumer point of view, filled with a pharmaceutical active ingredient, and as an example of a specific implementation, we have shown the following cases , corresponding to the scope of protection discussed in the independent clause of the formula:

Capsule 1 (see Fig. 1) has the shape of an ellipsoid of rotation, and on one of the ends it has a thickening of the wall 1, which is three times greater than the main thickness of the wall of the shell. The shell is made of an elastic elastic material, such as latex, polyurethane or rubber, and has an average thickness of 1.5 mm over the main part of the surface. and)

Stress concentrators Z are made in the form of conical recesses in the capsule shell. The capsule is filled with a liquid ingredient 4, for example: a local anesthetic, a medicine for the treatment of diseases of the oral mucosa, a medicine for the treatment of angina, or an oral hygiene product. Filling Ge! zo It is carried out with a double thin needle through a zone with a thickened wall.

The capsule 5 (see Fig. 3) has the shape of an ellipsoid of rotation, and on one of the ends it has a thickening of the wall, which exceeds by three times the main thickness of the wall of the shell, in this thickening, an opening 8 is made, which is closed with a stopper 7. The stopper 7 is installed on glue or fixed with thermostitching. The shell of the capsule 5 is made of an elastic inelastic material, and has an average thickness of 0.5 mm along the main part of the surface. 7

Stress concentrators 9 are made in the form of conical recesses in the capsule shell. The capsule through the hole 8 is filled with elastic twisted nylon monofilaments 10 and filled with a pharmaceutical active ingredient 11 by 85 95, for example: a local anesthetic, a drug for the treatment of diseases of the oral mucosa, a drug for the treatment of sore throat, or an oral hygiene agent.

Capsules 12 (see fig. 5) have a shell 13 of cylindrical shape and are made of a tube of silicone rubber "1 mm thick, the cavity of which is divided by transverse double thermal seams 14 and 15 through equal gaps with splu) with the formation of individual capsules connected to each other . The stress concentrators 16 are made in the form of disc recesses in the capsule shell. The capsule is filled with liquid 17, for example: local anesthetic, medicinal a drug for the treatment of diseases of the mucous membrane of the mouth, a drug for the treatment of angina, or a means of hygiene of the oral cavity.

Capsules 18 (see Fig. 7) have the shape of pillows, their shell 19 is connected by double thermal seams 20 and 21.

Go! Stress concentrators 22 are made in the form of conical recesses in the capsule shell. The capsule is filled with elastic nylon monofilaments 23 and a pharmaceutical active ingredient 24, for example: a local anesthetic, a drug for the treatment of diseases of the oral mucosa, a drug for the treatment of angina, or an oral hygiene agent.

When using a pharmaceutical dosage form in the form of capsules, a person squeezes the capsule with his teeth, as a result of which the membrane ruptures at the location of the stress concentrators and through the hole formed,

The medicine enters the oral cavity in a trickle. After the pressure is relieved, the capsule recovers its shape. When a person chews, he moves the capsule in his mouth and the medicine irrigates the entire oral cavity.

When the strength and intensity of chewing changes, the intensity of release of the drug from the capsule also changes. The capsule is chewed until the cavity is empty or until the moment when you get tired of chewing and throw it away. The elasticity of the capsule creates a pleasant chewing sensation. (F, For the production of the proposed capsules, traditional technology and materials for the well-established production of baby pacifiers, technological equipment for the production of polymer tubes for medical purposes can be used. 60 A pharmaceutical dosage form was obtained in the form of a hermetic capsule with an elastic shell, which makes it possible to take the drug for treatment of the mucous membrane of the mouth or any drug, the effect of which reaches maximum efficiency when absorbed through the mucous membrane, for example, treatment of angina, application for local anesthesia, use as a means of oral hygiene.

Claims (6)

The formula of the invention 1. Pharmaceutical dosage form with adjustable release and variable release rates, containing a polymer shell and one or more pharmaceutically active ingredients, which is characterized by the fact that the pharmaceutically active ingredient in a liquid or gel-like state is in a sealed elastic capsule made of a polymer insoluble in water, saliva and gastric juice to the membrane, which has tension concentrators. 2. Pharmaceutical dosage form according to claim 1, which is characterized by the fact that the voltage concentrators in the number of at least one are made in the form of conical depressions in the capsule shell. C. The pharmaceutical dosage form according to claim 1, which is characterized by the fact that the capsule shell is made of 70 elastic elastic material, for example latex, polyurethane or rubber, has a spherical shape, for example an ellipsoid of rotation or an ovoid, the average wall thickness along the main part of the surface within 0 .5-2.5 mm and local thickening of the wall, which exceeds 2-4 times the main thickness of the shell wall. 4. The pharmaceutical dosage form according to claim 1, which is characterized by the fact that the capsule with an elastic polymer shell is filled with elastic porous material or elastic twisted monofilaments and is filled with 75% of the pharmaceutically active ingredient by no more than 90%, has a local thickening of the wall of the shell, in which an opening is made , which is blocked with a stopper made of polymer material. 5. Pharmaceutical dosage form according to claim 4, which is characterized by the fact that the capsule shell has the shape of a "cushion". 6. The pharmaceutical dosage form according to claim 1, which is characterized by the fact that the shell has a cylindrical shape and is made of a polymer tube, the cavity of which is divided by transverse double thermal seams at equal intervals into separate capsules connected to each other by the wall of the shell. c schi 6) (o) in c "- d) - and? (ee) - ime) -i 3e) ime) 60 b5