ES2228398T3 - SYSTEM FOR THE ADMINISTRATION OF AN ACTIVE AGENT VIA ORAL. - Google Patents

Abstract

An oral active agent delivery system for delivering discrete units of active agent formulation in admixture with a fluid is disclosed. Said system comprises: a hollow active agent formulation chamber (10) having a first end (16) and a second end (18) and containing an active agent formulation in the form of a plurality of discrete units, said ends being adapted to pass fluid during delivery of the active agent formulation; and a fluid passing active agent retainer for preventing release of the discrete units from the first end (16) of the chamber while permitting fluid entry into the chamber; and is characterised in that said fluid passing active agent retainer comprises a restriction in the cross-sectional area of said first end of said chamber, and each of said discrete units has a diameter greater than said restriction. <IMAGE>

Description

Agent management system orally active

The present invention relates to the oral administration of an active agent. Plus particularly, to a device for administration via oral formulation of an active agent in the form of units individual mixed with a liquid, by inserting the individual units in a hollow cell for the formulation of active agent. A retainer at the first end of the cell prevents the output of the individual units from this end of the cell while allowing the flow of the liquid when a suction at the second end of the cell. Individual units they can be easily swallowed, mixed with the flowing liquid Through the cell.

For oral administration of active agents have been used tablets, capsules, oblong tablets and many other types of devices. These shapes are relatively easy to manufacture and convenient for use in hospitals, institutions and at home. In these Dosage forms have incorporated many different types of active agents - from analgesics to antibiotics and hormones.

There are patients who, due to their age or illness, have difficulty swallowing solid forms of presentation. According to Kikendall et al ., Digestive Diseases and Sciences 28: 2 (1983), between 1970 and 1982, 221 cases of esophageal lesions caused by ingestion of tablets and capsules had been documented. The drugs most frequently involved were tetracyclines (108 cases), emepronium bromide (36 cases), potassium chloride (16 cases) and ferrous salts (12 cases).

Document DE 1906964 discloses a suction device comprising of a cell containing a liquid or solid concentrated drink. For use, the concentrated in a liquid to form a drink as the liquid flows through the suction device to the mouth of the Username.

US 4792333 discloses a device for the administration of drugs comprising a tube suction sealed at both ends and with a constriction circumferential that prevents the movement of a single capsule of drug after constriction, along the suction tube. The user of the device holds the tube in such a way that the capsule rests on the constriction, cuts both ends of the tube and suction at one end, ingesting the capsule with the drug as part of a mixture with the liquid. Constriction It is located near this end of the tube.

The document EP-A-0383503 describes a system tubular for the administration to the patient of a therapeutic agent in the form of free flow. The therapeutic agent is contained in a tube through a fixed grid, permeable to liquids or in a loop formed in the tube. As the liquid is sucked through of the tube by the patient, the therapeutic agent is transported from the fixed grid or the loop through the liquid and dispensed to patient.

Some forms of oral dosage in which swallowing a system is avoided Large size solid, which is easy to use and manufacture.

According to the present invention, a oral administration system of active agents according to the claim 1 indicated below.

According to one embodiment, the individual units contained within the cell are in particulate form.

In a second embodiment, the units individual contained in the cell are in the form of multiple Dosage forms of the active agent.

The present invention provides a device for oral administration of a formulation of an active agent in the form of individual units, easy to manufacture and use, and can supply a predetermined amount of the active agent.

The expression "active agent formulation" refers to the active ingredient or drug, optionally combined with additional inert vegetables and ingredients, pharmaceutically acceptable.

The expression "individual units" is refers to the formulation of the active agent in solid form or particulate

An "oral dosage form" as described herein means the formulation of active agent contained in an individual unit that you can keep its physical configuration and chemical integrity when contained on the management device.

In this document, the expressions "therapeutically effective amount" or "therapeutically rate effective "refers to the amount or rate of active agent necessary to obtain the desired pharmacological result, with beneficial frequency.

The expression "retainer of the formulation of active agent "refers to a valve, plug, restriction or similar which prevents the active agent formulation from leaving the device. The "retainer of the active agent formulation at liquid passage "refers to a valve, plug, restriction or similar that allows the passage of liquids but not that of others ingredients, such as the formulation of the active agent contained in the administration device

The dispensing device of the invention is use when it is not convenient, or it is unsafe, use solid oral dosage forms, such as capsules or tablets The devices are particularly useful in populations of elderly or pediatric patients and also in those They have problems swallowing capsules or tablets. During a therapeutic program can be administered to these patients one or several of these devices.

Next, a description of the embodiments of the invention from an example and making Reference the attached drawings.

Fig. 1 is a cross-sectional view of a preparation of an embodiment of the administration device of the invention.

Fig. 2 is a cross-sectional view of a preparation of another embodiment of the device administration of the present invention.

Fig. 1 presents a sectional view. transverse, of an embodiment of the administration device according to the present invention. The device is ready before place it in the liquid. In Fig. 1 the device 40 is shown consisting of cell 42 for the formulation of the active agent. Within cell 42 there are multiple oral dosage forms, 44. The first end, 46, of cell 42 presents a retainer of the formulation of the active agent at the passage of the liquid, 54, prepared by narrowing of cell 42, such that the diameter of the opening, 48, is less than the dosage form, 44. Thus, the Dosage form, 44, will not leave cell 42. The second end, 50, contains a retainer for agent formulation active, 56, mobile shutter-shaped, 52. When operating, the first end, 46, of cell 42 is inserted into a liquid, the obturation, 52, and the second is brought to the patient's mouth extreme, 50. The patient then sucks from the second extreme, 50, in such a way that a mixture of liquid enters the oral cavity and a dosage form, which can be easily swallowed. The Dosage forms, 44, may be instant release, prolonged, continuous or controlled type, depending on the pattern of Desired release for the drug.

Fig. 2 is a cross-sectional view of a second embodiment similar to that shown in Fig. 1 but instead of the mobile shutter, the second end, 130, is sealed by a stop, 134, which can be completely removed before place the device in the liquid, 30, and administer the forms oral dosage, 44.

The active agent may be in liquid form, solid or semi-solid. The active agent formulation that contains said active agent may also contain other substances such as binders, coating substances or stabilizers, such so that the formulation is constituted in one or more units individual. Individual units can be designed in variable ways to provide a specific profile of drug administration An embodiment comprises a formulation in particulate form. These particles may present a diameter between 50 and 2,000 µm, generally between 100 and 500 µm. When the particulate material has a taste unpleasant, this taste can be masked by some procedures well known to those skilled in this field. The particles may have been designed for immediate release of the active agent, or be coated so that the slow or pulsed release of the active agent or for a combination of immediate, pulsed and / or slow release of the active agent. The particles may be coated by an enteric coating to provide a directed release of the active agent. Further, There may be formulations containing more than one active agent.

In other embodiments, the active agent may be in liquid form, contained in a soft gelatin capsule or in a solid oral dosage form. These forms of Dosage can be matrix or other tablets, "pellets" and oblong tablets in which the relationship between The height and diameter is greater than the unit, capsules, pumps elementary osmotic as described in US Patent No. 3,845,770, miniosmotic pumps as described in the documents No. 3,995,631, No. 4,934,756 and No. 4,111,202 and osmotic systems multicell referred to as osmotic pumps "push-pull" and "push-melt", as described in US 4,320,759, 4,327,725, No. 4,449,983 and No. 4,765,989, which are incorporated as references.

The following is a method for determination of the active agent release profile of the forms of solid dosage:

n = x + y + z

n = total number of units individual in the device

x = individual release units immediate

y = individual release units constant

z = individual slow release units

A constant release is obtained when x = z = 0; a two-pulse release occurs when y = 0. When neither x ni y ni z = 0 there will be a pressed / constant / pressed release. Such systems provide large capacity devices with the possibility of one dosage per day.

The term "active agent" refers to a agent, drug, compound or composition of substance or mixture of substances that provide some pharmacological effect, with beneficial frequency. This includes food, supplements food, nutrients, drugs, vitamins and other agents beneficial. In the present context, the term also includes any physiologically or pharmacologically active substance that produces a localized or general effect on a patient. The active drug that It is administered includes antibiotics, antiviral agents, antiepileptic, analgesic, anti-inflammatory and bronchodilator and can be inorganic and organic compounds, including, although without being limited to them, the drugs that act on the peripheral nerves, adrenergic receptors, receptors cholinergic, skeletal muscle, cardiovascular system, smooth muscles, the circulatory system, synapses, joints neuroefectors, endocrine and hormonal systems, the system immune, reproductive system, skeleton, systems autacoids, digestive and excretory systems, the system of the histamine and the central nervous system. The appropriate agents they can be selected, for example, among the polysaccharides, steroids, hypnotics and sedatives, psychic invigorators, tranquilizers, anticonvulsants, muscle relaxants, agents antiparkinsonian, analgesic, anti-inflammatory, contracting muscular, antimicrobial, antimalarial, hormonal agents, including contraceptives, sympathomimetics, polypeptides and proteins capable of causing physiological effects, diuretics, lipid regulating agents, agents antiandrogenic, antiparasitic, neoplastic, antineoplastic, hypoglycemic agents, nutritional agents and supplements, supplements of growth, fats, ophthalmic agents, antienteritis agents, electrolytes and diagnostic agents.

Examples of active agents useful in this invention include prochlorperazine edisilate, sulfate ferrous, aminocaproic acid, mecamylamine hydrochloride, Procaynamide Hydrochloride, Amphetamine Sulfate, methamphetamine hydrochloride, benzfetamine hydrochloride, Isoproterenol Sulfate, Phemetrazine Hydrochloride, Chloride of betanecol, methacholine chloride, hydrochloride pilocarpine, atropine sulfate, scopolamine bromide, Isopropamide iodide, tridihexylethylchloride, hydrochloride fenformin, methylphenidate hydrochloride, colinate theophylline, cephalexin hydrochloride, diphenidol, Meclizine Hydrochloride, Prochlorperazine Maleate, phenoxybenzamine, thiethylperazine maleate, anisindione, diphenadione, erythritol tetranitrate, digoxin, isoflurophate, acetazolamide, metazolamide, bendroflumetazide, chlorpropramide, tolazamide, acetate chlormadinone, fenaglycol, allopurinol, aspirin with aluminum, methotrexate, acetyl sulfisoxazole, hydrocortisone, hydrocorticosterone acetate, cortisone acetate, dexamethasone and its derivatives, such as betamethasone, triamcinolone, methyltestosterone, the 17-b-estradiol, ethinyl estradiol 3-methyl ether, prednisolone, acetate 17-b-hydroxyprogesterone, the 19-nor-progesterone, norgestrel, Norethindrone, Norethisterone, Norethiederone, Progesterone, norgesterone, noretinodrel, aspirin, acetaminophen, indomethacin, naxoprene, fenoprofen, sulindac, indoprofen, nitroglycerin, isosorbide dinitrate, propanolol, timolol, atenolol, alprenolol, cimetidine, clonidine, imipramine, levodopa, chlorpromazine, methyldopa, dihydroxyphenylalanine, calcium gluconate, ketoprofen, ibuprofen, cephalexin, erythromycin, haloperidol, zomepirac, ferrous lactate, vincamine, phenoxybenzamine, diltiazem, milrinone, captopril, mandol, quanabenzo, hydrochlorothiazide, ranitidine, flurbiprofen, fenbufen, fluprofen, tolmetin, aclofenac, mefenamic acid, flufenamic acid, difuninal, nimodipine, nitrendipine, nisoldipine, nicardipine, felodipine, lidoflazine, lisoniprile, thiapamil, enalapril, captopril, ramipril, enalaprilat, famotidine, nizatidine, sucralfate, ethinididine, tetratolol, minoxidil, chlordiazepoxide, diazepam, amitriptyline and imipramine. Other examples are proteins and peptides that include, but are not limited to, insulin, the colchicine, glucagon, thyroid stimulating hormone, parathyroid and pituitary hormones, calcitonin, renin, prolactin, corticotrophin, thyrotropic hormone, hormone Stimulating follicle, chorionic gonadotropin, hormone gonadotropin releasing, bovine somatotropin, oxytocin, vasopressin, prolactin, somatostatin, lipresin, Pancreozyme and luteinizing hormone.

It must be understood that in the formulation of the agent active you can incorporate more than one active agent in a device of this invention and that the use of the term "agent" of any way discards the use of two or more of them.

Agents can be in various forms, such as soluble and insoluble molecules, charged or uncharged, such as components of molecular complexes or pharmacologically salts Acceptable non-irritating.

The amount of active agent used in the administration device will be the amount needed to supply a therapeutically effective amount of the agent to Achieve the desired result. In practice, this amount will vary widely, depending on the particular active agent, of the severity of the condition and the desired therapeutic effect. Do not However, the device is generally useful for agents assets that must be administered in fairly high doses, of about 100 mg to 5,000 mg, usually in the range between 250 mg and 2,500 mg, approximately. However, as the devices they can also be useful for pediatric patients, doses between 25 and 250 mg are also contemplated.

Representative materials for the manufacture of the devices, including the formulation cell of the active agent, the elongated tubular segment and the closures and end stops include, without limitation, paper, plastics such as propylene / styrene copolymers, polypropylene, high density polyethylene, low density polyethylene and Similar. Generally, the devices have a diameter internal between 3 and 8 mm and the wall thickness ranges between 0.1 and 0.4 mm. The length of the devices ranges from 10 and 30 cm

The active agent formulation retainer at the passage of the liquid allows the free flow of the liquid medium but prevents the passage of the active agent formulation from the device before administration.

The liquid used for the suspension of the formulation of the active agent by suction through the cell Formulation should preferably be a flavor liquid nice, including, without limitation, water, juices, milk, soda, coffee, tea, etc. You must ensure its compatibility with the active agent formulation.

The following example illustrates the present invention. It has not been built as a limiter of the scope of the same.

Examples Example 1

The administration device according to the The present invention was prepared as follows. They were heat sealed one of the ends of the large size tubes with a diameter internal of 0.21 inches and a length of 6 inches. The extreme sealed was partially cut, so that the hole resulting presented a diameter of less than 5 mm.

They were prepared as follows small elemental osmotic pumps of calcium ascorbate. He Nuclear compartment was formed with 50 mg of calcium ascorbate, 2.7 mg of polyvinylpyrrolidone and 0.6 mg of magnesium stearate. Be mixed the ingredients well and compressed in a press Manesty, with a 3/16 inch round punch and using a pressure of 1½ tons. A 5 mg semipermeable wall formed by mixing 80% cellulose acetate with an acetyl content of 39.0%, 10% sorbitol and 5% polyethylene glycol 400. The solution was spray-coated in the nuclear compartment with a solvent consisting of 714 ml of acetone and 186 ml of water in a air suspension machine. The coated osmotic tablet is dried for 72 hours at 50 ° C. A 0.2 mm hole was drilled in the wall.

Twenty of these small systems were placed osmotic, with a total dose of 1,000 mg of calcium ascorbate inside the tube, from the open end. He plunged into a glass of water the partially sealed end of the tube. The twenty little ones Dosage forms were easily sipped with a slight suction, providing a prolonged release of vitamin C.

Claims (13)

1. Oral administration system of an agent active (40) to supply individual units (44) of one formulation of an active agent mixed with a liquid, said system comprising: a hollow cell for agent formulation active (42; 132), with a first end (46) and a second end (50; 130) containing an active agent formulation (44) whose ends (42; 50; 130) are adapted for the passage of the liquid during administration of the active agent formulation; Y an active agent retainer as the liquid (54) to prevent the exit of the individual units of the first end (46) of the cell while allowing the liquid enter the cell; characterized in that said formulation of the active agent may be in the form of a plurality of individual units and said first end is the distal end of the system and said second end is the proximal end of the system and said retainer of the active agent passing the liquid (54) it comprises a throttle in the cross-sectional plane of the formulation cell (42; 132) at said first end (46) and each of said individual units (44) has a diameter greater than said throttle to prevent the passage of said units individual (44) from said first end (46), said formulation cell being configured such that by inserting said end (46) into a liquid and sucking at the second end (50; 130) said individual units are administered by the second end (50; 130) mixed with said liquid. 2. An orally active agent delivery system according to claim 1, characterized in that said formulation cell (42; 132) is bent at said first end (46) forming said throttle. 3. Administration system according to claims 1 or 2, further comprising a retainer of the active agent formulation (52; 134) at the second end (50; 130) of the active agent formulation cell (40; 132) for prevent the exit of said formulation of the active agent from said second end (50; 130) before use. 4. Administration system according to claim 1, wherein said individual units are select from the group consisting of particles, forms of oral dosing and combinations thereof. 5. Administration system according to claim 4, wherein said individual units provide prolonged administration of the active agent of said formulation. 6. Administration system according to claim 4, wherein said individual units provide immediate administration of the active agent of said formulation. 7. Administration system according to claim 4, wherein said individual units provide a pulsed administration of said active agent of said formulation. 8. Administration system according to claim 4, wherein said individual units comprise oral dosage forms comprising a layer Osmotic and a layer with an active agent. 9. Administration system according to claim 1, further comprising an surrounding end cap concentrically the first end (46) of the cell. 10. Administration system according to claim 3, wherein said formulation retainer of the active agent (52; 134) at the second end (50; 130) of the cell It comprises a rotary valve. 11. Administration system according to claim 3, wherein said formulation retainer of the active agent (52; 134) at the second end (50; 130) of the cell comprises a throttle at the second end (50; 130) of the cell. 12. Administration system according to claim 2, wherein said formulation retainer of the active agent (52; 134) of the second end (50; 130) of the cell It comprises a removable end cap. 13. Administration system according to claim 1, wherein said active agent formulation comprises an active agent selected from a group consisting of antibiotics, antiviral agents, antiepileptic agents, analgesics, anti-inflammatory agents and bronchodilators.