FI123712B - New swallowing aid - Google Patents

Description

New swallowing aid

Field of the Invention

The present invention relates to the field of oral and pharmaceutical administration of pharmaceutical and nutritional products, and more particularly relates to a swallowing aid for use with discrete and intact solid dosage forms of pharmaceutical and nutritional products intended for oral administration.

Background of the Invention

The prevalence of dysphagia (that is, swallowing difficulty) in non-adolescents over 65 years of age is approximately 15% and is even higher (30-10%) in the population over 75 years (Roy, N. et al., Ann Otoli Rhinoli Laryngol 2007, 116 (11): 858-65, Chen, PH et al., Dysphagia 2009, 24 (1): 1-6). However, the absolute number of people suffering from NIE problems will increase significantly when patients with certain diseases are included and all age groups are included. The most common diseases that cause swallowing problems are stroke (prevalence 15 million worldwide), chronic obstructive pulmonary disease (COPD; prevalence higher than 13 million in the US) and Alzheimer's disease (prevalence in the US 4 million). For example, the incidence of dysphagia in stroke patients is 80% (Ha, L. et al., Tidsskr Nor Laegeforen 2008, 128 (17): 1946-50).

The swallowing process is a complex reflex that requires complete synchronization of the muscles involved in swallowing and breathing (Logeman, J. A. et al., Folia Phoniatrica Logopaedica 1998, 50 (6): 311-319). The coordination of these muscles can be impaired even without any specific disease. Also, dry mouth symptoms are not uncommon. Therefore, dysphagia is not only a problem experienced by older people but can also cause problems in young people with dysphagia caused by psychological factors. Symptoms associated with swallowing problems include coughing, clearing or throat blocking before or during or after eating or swallowing a drug, and feeling of an object in the throat (Palmer, JP et al., Am Fam Physician 2000; 61: 2453-62 ).

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The major problem with swallowing small tablets is that the m o subject has no precise knowledge of where the tablet is in the mouth so that he can coordinate tongue and cheek muscle movement to move the tablet to the correct position and swallow. An analogous problem arises when the patient is 35 incapable of coordinating the cheek muscles and tongue.

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Usually the tablet is swallowed with water or other liquid drink immediately after the tablet is placed in the mouth. However, some people have problems with swallowing reflex, which can cause water to be inhaled into the lungs.

5 For large tablets or capsules, the subject may feel uncomfortable when a hard object is pressed firmly against the hard nozzle, mouthpiece, during the ingestion process. In addition, in some people, attempting to swallow a tablet or capsule may trigger a vomiting reflex.

Oral administration of tablets and capsules is often problematic also in animals, although it is often not directly due to difficulty in swallowing. Instead, animals simply do not consent to oral administration of the drug, and it is not always easy to get the tablet into the mouth where the animal cannot spit it out.

Although the prevalence of dysphagia is extremely high, and although it makes daily life difficult, especially for older people, little has been done to eliminate or alleviate the problems associated with it. In the elderly, daily oral administration is one of the most striking events where swallowing problems can reduce the quality of life.

20 Swallowing aids in the form of a spray (Pill Glide Spray, FLAVORx, USA) or a swallowing cup (ORALFLO, Oralflo Technoliogies, USA) are available on the market to assist a patient with swallowing problems. In addition, a solid product is currently commercially available which is intended to facilitate the ingestion of tablets and capsules (MedCoat®, Med Coat AB, Sweden). The product comprises 25 films wrapped around a tablet. The membrane becomes slippery when it gets wet in the mouth, which is thought to aid in the swallowing process. However, this system does not soften the contact of the hard tablet with the mouthpiece, and therefore does not eliminate the unpleasant feeling that some people experience during tablet swallowing. Also, the slippery film does not act as an active carrier carrying the tablet to the swallowing reflex trigger zone. In addition, the film winding Wrapping around your tablet can be a daunting task for older people because oops it requires clever fingers. Further, despite the slippery film, it is still possible to drink water while taking tablets and capsules. Further literature discloses additional products, either to assist the ingestion process or to facilitate the taking or use of a drug or other solid product.

3 U.S. Patent No. 6,337,083 B1 describes a method and composition for oral administration of solid pharmaceuticals or nutritional supplements, wherein the ingestion of solid bodies, e.g., tablets and capsules, is accomplished by admixture with a liquid base. When the oral dosage composition is drunk after being placed in the mouth, the tablet floats and advances and is finally swallowed due to various physical properties (e.g., higher viscosity) of the dosage composition compared to a liquid base (usually water or juice). The viscosity of the oral administration composition is 10 to 20 centipoise (centipoise = mPa-s), which means that the composition flows as a rather thick homogeneous liquid. This prior art oral dosage composition is in a liquid form or is formulated with solids immediately before use by adding a liquid base.

WO2007 / 035117 A1 discloses another device for the oral administration of systemic drugs comprising a semi-solid agar gel bolus containing dispersed active ingredients in various forms such as granules or coated granules (microcapsules). The active ingredients are released when the bolus breaks in the mouth.

EP 0651997 B1 describes capsule-free bolus preparations made from agar for use in the administration of drugs through the sinus cavity. These boluses are hard enough to withstand pushing through the bubble. The active ingredients are suspended in the described boluses, which are intended to be broken down in the buccal cavity.

WO2004 / 037231 A1 describes capsule formulations for medical use, wherein the film-forming composition of the capsule shell comprises an acacia and a water-soluble polymer. These capsule shells have good mechanical strength and low brittleness and may contain drugs as fillers.

EP 0389700 A1 describes capsules containing a large number of soft-walled microcapsules prepared by the drop method. Some of the properties of the capsule film in these capsules, such as water solubility and heat resistance, differ from those of soft capsules made of gelatin base material.

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EP 0950402 B1 describes a chewable drug having a gelatin matrix which can be swallowed quickly and easily. The gelatin matrix contains dispersed active pharmaceutical ingredients in a ready-to-use formulation.

WO2004 / 067041 A1 discloses formulations of semi-solid, capsule-free non-woven beads for dispensing toothpaste into the mouth, which rapidly break under the force applied. These beads are not intended to be swallowed. The active ingredients are finely dispersed or dissolved in the beads.

Prior art solutions are not sufficient to solve the problems associated with the ingestion of solid forms of pharmaceutical or nutritional products such as tablets, pills and capsules. Thus, new instruments are needed in this area.

Brief Description of the Invention

The present invention solves widespread swallowing problems by providing new devices and methods to facilitate oral administration of solid forms of pharmaceutical or nutritional products.

It is an object of the present invention to provide a swallowing aid for carrying solid bodies which serves as both a storage container for an oral vehicle and an applicator device, which in turn consists of a semi-solid bolus and lubricant. The swallowing aid si-20 contains an oral vehicle to facilitate ingestion of solid dosage forms of pharmaceutical or nutritional products in humans. The semi-solid bolus carries these products during the swallowing process and also softens the oral contact with the solid dosage forms.

The present invention provides a novel oral vehicle 25 in combination with a dosing or applicator device and a method for

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^ ingestion of some pharmaceutical or nutritional products becomes easier and, in extreme cases, even possible in subjects suffering from swallowing problems.

O) 9 The invention further provides a new type of insertion device for a semi-solid bolus that serves as both an applicator and a storage device for the bolus.

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The present invention relates to a swallowing aid for solid product administration, wherein said swallowing aid comprises: a) an oral vehicle comprising a semi-solid bolus made from a non-stick material such as a gel or a paste; a viscous fluid surrounding the bolus; and c) a applicator device such as a bubble tube pack.

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The ingestion aid device according to the present invention has the features described in detail in the specification and the appended claims.

The present invention further relates to the use of a swallowing aid for the administration of solid forms of pharmaceutical or nutritional products.

Brief Description of the Drawings

Figure 1 illustrates examples of alternative ways of making cup tube packages.

Figure 2 shows an example of a blister tube pack set / set.

Figure 3 shows examples of different dimensions and shapes of blister tube packages according to the invention.

Figure 4 illustrates a method of using a pre-filled blister tube package according to the present invention for administering a tablet or capsule.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a swallowing aid for a solid pharmaceutical or nutritional product. In particular, the swallowing aid device of the present invention includes an oral vehicle based on a non-flowable dispersion system such as a gel, paste, oil in water emulsion or water in oil emulsion formed in a semi-solid bolus capable of substantially maintaining its shape. The semi-solid bolus of the invention is surrounded by a lubricant fluid that allows the bolus to slide freely from its applicator.

The bolus of the present invention has a semi-solid composition and properties that allow it to maintain its shape without any support vessel.

$ 2 The term "bolus" refers to a preparation having the shape of a cylinder, a truncated o ™ cone, an elongated oval, a rounded triangle, a polygon, and the like, made of a non-flowable material as described below.

The bolus is also characterized in that its internal cohesive forces maintain the mass of the bolus as a whole, even when the exterior forces of considerable height change the shape of the bolus.

00 £ j The term "semi-solid" refers to a highly viscous formulation.

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o tensile preparations containing a single or mixed base in which one or more substances have been dissolved or dispersed. The bolus base of the oral delivery device of the present invention has a viscosity of greater than 6,000,000 centipoise (mPa.s) at 20 ° C, preferably 100,000 to 2,000,000 centipoise, as measured by Fibrillation Viscometer (FISER).

The dispersion system used to prepare the bolus of the invention is a gel, a paste, an oil-in-water emulsion or a water-in-oil emulsion. It may also be a mixture of two or more of these colloidal dispersions. Alternatively, these colloidal dispersions may also form layers on top of one another or surround each other in a shell-like manner. In particular, a bolus made of sugars and / or proteins may also have a foam structure (see below). Preferably, the bolus is comprised of the individual pure constituents 10 described below. However, it can also advantageously be prepared from natural materials such as specifically processed vegetables or animal fat and meat as well as dairy products by adjusting the viscosity of the final bolus so that it has a semi-solid composition and properties that allow the bolus to remain in any form. In addition, it can be prepared from a mixture of pure colloidal dispersion systems and natural products.

Gels and pastes, two subgroups of these dispersion systems, play a major role in the present invention because of their structure, they readily deform under the effect of the applied force, but generally retain their predetermined shape when the force is removed, unless the deformation exceeds a certain limit. The force of gravity is less than that limit, and therefore the shape remains without any support vessel.

In particular, gels also have viscoelastic behavior, which helps to carry solid bodies while the gel bolus slides through the mouth and throat. However, somewhat less viscous "ointment type" emulsion formulations are also included within the scope of the present invention. Idea fluids with clear flow characteristics are not the main components of the present bolus o. Instead, they are used as lubricants in the oral vehicle

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^ at the interface between the bolus and the blister.

Gels consist of liquids which have been gelled with suitable gel-forming agents, thereby forming a non-sticky, adherent mass which | la has strong cohesive forces but low shear. The molecular gap structure of a gel consists of a network of long, varying crosslinked or intermixed gelling agent fibers that support or contain other molecules. Hydrophilic gels (hydrogels) are formulations of a water miscible liquid vehicle, such as water, buffer solutions, glycerol or propylene glycol, which have been gelled with a suitable gelling agent. Lipophilic gels (oleogels) are, for example, formulations containing, for example, fatty oils gelled with colloidal silica or aluminum soaps.

Generally, the gelling agents are polysaccharides or other polymeric compounds. Suitable gelling agents include starches, plant oils, proteins, cellulose derivatives, carbomers, poloxamers, and magnesium aluminum silicates. Specific examples of gelling agents include, but are not limited to: cellulose ethers, guar gum, guar gum derivatives, locust bean gum, psyllium, acacia, tracanth gum, carrageenan, agar, algin, xanthan, scleroglucan, dextran, pectin, pectin. Gelants of animal origin include, for example, gelatin made from collagen extract, egg white and the like. Naturally occurring seaweed produces gels whose structure is based on polysaccharide chains, including polymers of D-mannuronic acid or L-guluronic acid (examples include alginic acid and its salts), or sulfated galactans (examples include agar, porphyran, capsa iota- and gamma-carrageenan), or combinations, analogs or derivatives thereof. Examples of food grade structural gels include mixtures containing one or more of gelatin, agar, carrageenan, locust bean gum, guar gum (guaran), pectin, alginates, cellulose derivatives (e.g., carboxymethylcellulose) and starches.

Preferred gels and gelling agents used to prepare the semi-solid bolus of the invention are alginates and cellulose derivatives.

The pastes are semi-solid preparations containing a high proportion, e.g. 5 to 60%, preferably 20 to 30%, of solids finely dispersed in the base. As with gels, the pasta base is usually a liquid medium such as water, buffer, glycerol or propylene glycol,

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but less than that in the gel. Solids in the paste include, for example, any fragments of plant parts (eg vegetables and herbs) and water-insoluble substances extracted from plants (eg cellulose).

| Typically, the concentrations of various substances in the bolus are adjusted such that the bolus retains 40-100% of its shape after sliding out of the applicator, such as a bubble tube package. The degree of shape retention is determined by measuring and comparing the maximum height of the bolus. height to the opening diameter of the blister tube package.

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The content of gelling agents in boluses ranges from 1 to 10%, and the preferred amount is 3 to 6% (e.g. for alginate) and 1-5% (e.g. for hydroxypropylmethylcellulose). When the oil-in-water emulsion is one of the components of a bolus, the vegetable oil used in its manufacture ranges from 5 to 30% (expressed as a percentage of the weight of the bolus), preferably from 7 to 15%, and in the water-in-oil emulsion. %, and the preferred amount is 60-70%.

The concentration of the emulsifier is adjusted according to the amount of the internal phase of the emulsion and may be from 1 to 10% of that amount, preferably from 3 to 6%. Suitable emulsifiers for oil-in-water emulsions include substances having an HLB value of between 8 and 18, such as sorbitan monolaurate, polyoxyethylene lauryl ether, polyoxyethylene monostearate, triethanolamine oleate, polyoxyethylene sorbitanane monolaurate, polyol ethylene monourea, and. Suitable emulsifiers for water-in-oil emulsions include substances having an HLB of between 4 and 6, such as sorbitan monooleate, stearate, palmitate and propylene glycol monolaurate. Various types of emulsifiers may also be mixed to obtain the desired HLB for both water-in-oil and oil-in-water emulsions.

In some embodiments of the present invention, solids in pastes may further include various fibers for treating constipation in bed-bound patients. included in the bolus formulations of poorly digestible plant fibers stimulate intestinal motility and, therefore, provide additional functional benefits in subjects suffering from constipation. Water insoluble microcrystalline cellulose also serves as an example of a fiber suitable for this purpose. Other suitable fibers include psyllium fibers and flax seed fibers. In the preparation of pastes, the water-insoluble fiber content is between 5 and 60%, preferably between 20 and 30%.

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Similarly, the paste (or gel) may contain lactic acid bacteria to maintain normal gastrointestinal function. This is particularly advantageous when the oral vehicle of the present invention is used as an antibiotic to facilitate the ingestion of waiting.

oo The base may be composed of natural or synthetic materials and may consist of a single-phase or multi-phase composition. Depending on the nature of the base, the formulations may have hydrophilic or hydrophobic properties.

00 35 Nutritional additives with the desired aroma (approved by the World Health Organization) can be used as flavoring agents to increase the acceptability of humans and animals 9 by oral ingestion of the present invention. Swallowing is made more pleasant, for example, by adding a synthetic flavor to the bolus and / or lubricant. For example, 1-p-menthene-8-thiol has a tropical fruit scent and is thus a suitable flavor. In addition to these 5 compounds, the taste and also the color of the bolus can be modified with various berry extracts (eg blackcurrant extract (E 163)) and fruits (eg organic apple flavor). Flavors of this kind are examples of substances suitable for humans and herbivores. For carnivores, the odor of meat and roast is obtained, for example, by adding the desired amount of 3- (methylthio) propanol or 2-methyl-3-10 tetrahydrofurantiol to the bolus.

In some cases, it may be desirable to mask the unpleasant taste of the ingredient (s) used in the preparation of the oral vehicle. This can be accomplished, for example, by the addition of (qs) sweeteners such as various natural sugars and sugar alcohols, e.g., saccharide, sorbitol and xylitol, and / or sweet-tasting synthetic compounds (potency sweetener), e.g., saccharin, cyclamate, aspartame, acesulfame K, sucralose and the like, at the base of the bolus and / or lubricant.

In addition, coloring agents, such as artificial coloring agents (Sunset Yellow FCF, Brilliant Blue FCF, Allura Red AC and the like) and natural coloring agents (caramel, betaine and the like), especially to improve children's acceptability ), can be added to the bolus base and / or lubricant.

Flavorings, sweeteners, and colorants are added in sufficient amounts, usually from 1 to 30 ppm of sweeteners, from 1 to 5% of sweeteners, from 0.001 to 0.01% of power sweeteners, and from 0.001 to 0.5% of dyes.

To prevent microbial contamination of the oral vehicle, small amounts of preservatives, e.g., parabens such as methylparaben, ethylparaben

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and propylparaben, sorbic acid and its salts such as potassium and calcium sorbate, benzoic acid and its salts such as sodium, potassium and calcium benzoate and the like are added to the bolus base. Preservatives are used for pi | otherwise 0.1-0.3%.

In the oral vehicle of the invention, the bolus is surrounded by a free-flowing lubricant. It facilitates sliding the bolus out of the applicator device, such as the blister tube pack into which it is packed, into the mouth, and finally down the throat. The lubricant is a non-viscous liquid, for example water, a vegetable oil containing only a small amount (e.g. <1%) of free fatty acids such as sunflower oil, corn oil and rapeseed oil, a mixture of water with a vegetable oil and an emulsifier such as a polysorbate derivative. to obtain an oil-in-water emulsion, a dairy product in the form of an oil-in-water emulsion such as cream, diluted yoghurt and whole milk.

The amount of lubricant is determined by the size of the applicator device, such as the blister tube package, and varies from the minimum amount required to moisten the surface of the bolus (e.g., 0.05-0.5 ml) to 20 ml for human and 100 ml liquid for larger animal oral vehicle. For use in humans, the volume of lubricating fluid is preferably 0.5 to 10 ml, more preferably 10 to 10 ml, and most preferably 1 to 5 ml.

The term "oral vehicle" refers to the semi-solid bolus of the present invention together with the lubricating fluid. The former is used to carry solid bodies, while the latter facilitates the sliding of the bolus.

The oral vehicle of the present invention serves as a carrier for solid dosage forms. The present oral vehicle is used to deliver dosage forms of medicaments and food products intact through the mouth and is not intended to release or release active agents into the mouth when they are carried by the bolus of the present invention.

A solid dosage form such as a tablet or capsule is placed at the tip of a non-flowing gel or paste bolus of the invention. The semi-solid structure allows the tablet or capsule to be added to the gel and immersed therein. Alternatively, the tip of the bolus may include an opening such as an incision, a notch, or a hole into which the tablet or capsule is inserted. Due to the semi-25 solid structure of the bolus, the bolus material completely surrounds the tablet or capsule. Not only does this aid in swallowing, it also covers the potential unpleasant taste of the tablet or Kap-5.

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The oral vehicle of the present invention is loaded with solid dosage forms (e.g., tablets and capsules) of pharmaceutical or O) nutritional products just prior to use. Thus, the present invention provides active pharmaceutical and nutritional agents the ingredients are administered intact in their normal dosage forms without direct contact of the active ingredients with the bolus matrix. In this respect, the oral vehicle of the invention differs substantially from the prior art. formulations, such as those described in WO2007 / 035117, EP 0651997 B1, 0035 WO2004 / 037231 and EP 0950402 B1, containing the active substances dispersed or suspended therein.

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Oral vehicles of the invention of the same size and diameter may be used to administer a variety of solid pharmaceutical or nutritional products, such as drugs for hypertension, high cholesterol, analgesics and the like, provided the tabs are of similar size. Thus, a patient with multiple daily medications will need only one size or only two or three different sizes of the ingestion aid of the present invention. Further, for relatively small tablets, the oral vehicle of the present invention allows two or more tablets to be swallowed simultaneously.

The semi-solid bolus of the present invention is preferably in the form of a cylinder or an almost cylindrical shape such as a truncated cone. However, the semi-solid bolus can be (molded) into any suitable shape such as an oval, rounded triangle or rounded polygon. Depending on the applicator, the choice of the ideal bolus diameter for a particular application will depend not only on the anatomical factors but also on the size of the tablet or capsule to be swallowed or administered. The diameter of the bolus should be at least 2 mm, for example 2.5 mm or 3 mm, larger than the diameter of the tablet or capsule to properly immerse these solid products at the tip of the bolus.

The cylindrical or nearly cylindrical bolus has a diameter of -20 and is usually in the range of 5 to 50 mm. Especially for human use, the bolus diameter is preferably 6 to 12 mm for children and 10 to 20 mm for adults. For veterinary use, the optimum diameter is 6-12 mm for small pets, 10-20 mm for large pets and small pets, and 20-40 mm for large pets.

The length of a semi-solid bolus can vary from 2 to 20 cm. There are two things to consider at the same time when deciding on the ideal length o of a bolus for a particular purpose. The first thing is the anatomical distance

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from the point where the blister tube pack contacts the lips to the mouth where the swelling reflex trigger zone is located. Another is the requirement that the bolus should be long enough so that it does not easily turn transversely in the mouth. | In this way, it is ensured that the tablet or capsule, which is pressed inside the tip of the bolus, reaches the swallowing launch zone. The excess weight of the gel or paste relative to the tablet or capsule does not cause any harm, although it may require additional ingestion. This is because the large mass of the boil helps the tablet or capsule slide down the throat. .

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The following lengths are preferred for boluses: in humans, 20 to 30 mm for children and 30 to 60 mm for adults; animals 20-30 mm for small pets, 30-60 mm for large pets and small pets and 100 to 200 mm for large pets. These lengths are equal to the corresponding dimensions of the insertion means, such as blister tubes, cylindrical or truncated conical parts. The overall length of the applicator is preferably 10-30 mm longer than the length of the bolus due to the space reserved for the lubricant at the bottom of the applicator.

In the present invention, the bolus is surrounded by a liquid or liquid film 10 between a semi-solid bolus and an applicator device such as a bubble tube package. The bolus material, which has relatively poor sliding properties, is packaged, for example, in a blister tube package with a base portion suitable for a larger volume of lubricant solution.

The inserting device has practically the same diameter as the bolus 15 (see text above). However, the length of the insertion means may be somewhat different. Depending on how slippery the bolus surface is, you may need to use different amounts of lubricant. In the case of insufficient sliding properties, a larger space is provided at the bottom of the applicator for lubricating fluid. This requires increasing the length of the insertion device roughly 10-20 mm by 30 mm compared to the length of the bolus. In some cases, it is necessary that you effectively push the bolus through the entire cylindrical portion. For this purpose, its base is shaped to form an almost sphere having a maximum volume equal to the remainder of the applicator. To further facilitate the sliding of the bolus, the cylinder portion of the applicator may be modi fi ed so that the tube opening is slightly wider than the diameter at a point near the bottom. This insert device model then has a truncated cone

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5 shape.

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The applicator of the ingestion aid of the present invention is a reservoir, a small plastic bottle or a plastic tube for holding and storing an oral vehicle. A preferred applicator is a blister tube package. Blister packing is made of a thin sheet of polymer, preferably 0.150-0.300 mm. The polymer may be a polyvinyl chloride (PVC), polyethylene (PE) or polypropylene (PP) polymer, which polymers are sufficiently durable to remain undamaged when the bottom of the blister tube package is pressed to force the bolus to slide out of the blister tube package. The preferred polymer is PVC.

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Polychlorotrifluoroethylene (PCTFE) can be laminated to PVC for a better moisture and oxygen barrier. Double structures such as PVC / PCTFE and triple laminates such as PVC / PE / PCTFE may also be used. Cyclic olefin copolymers (COC) or polymers (COP) also provide a moisture barrier to blister packs typically in multilayer combinations with PP, PE or glycol modified polyethylene terephthalate. The quality of the polymers should meet the specifications set for product materials in the food and / or pharmaceutical industry. The thickness of the laminate (s) should be between 0.015 mm and 0.100 mm.

Blister tube packages are made from a plastic polymer sheet by thermoforming using high pressure and / or physical force to lining the desired molds. The edge of the opening of the blister tube package is smoothed by bending the polymer plate over the round edge of the mold or by attaching a separate smooth ring to the edge of the blister tube package.

The cooled blister packs are then filled with oral vehicle and sealed immediately with aluminum foil or plastic film in a heat sealer. The bubble packing technology is advantageous in the preparation of the desired vials (tubes) for the oral vehicle of the present invention, but tubes of possibly the same dimensions and materials may also be manufactured individually e.g.

20 injection molding machines.

Another preferred insertion device according to the invention is a sachet made of plastic, i.e., the polymers described above for the blister tube package, or aluminum foil or liquid-resistant cardboard. For example, in the case of extremely sliding boluses, it is not necessary to facilitate the sliding with the squeegee at the bottom of the tube. Thus, the insertion device can be made of a liquid-resistant board laminated with one or more of the following polymers: PE, PP, PCTFE, COC, COP and glycol modified polyethylene terephthalate.

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This type of applicator can be manufactured using technology well known in the art for such liquid-resistant cartons.

The resulting sachet may have three or more levels of wall construction mass, and the cross-sectional geometry of the sachet may be any of the following: triangle, o square, pentagon, hexagon, hexagon, and octagon. The bottom structure of this type of sachet is flat. The opening of the sachet is flanked / closed by a separate smooth edge made of a plastic polymer.

00 35 This type of sachet is also characterized in that it is sealed with 14 aluminum foil or polymer film in analogy to the blister tubes. The shape of the dose pouch then also defines the shape of the bolus.

The dimensions and shapes of the blister tubes and sachets may vary depending on whether they are used to facilitate the taking of solid bodies (tablets, Kap-5) in human or animal medicine. Figure 3 illustrates, by way of example, different blister tube packaging designs. Sliding the bolus packed into the barrel of the blister pack is assisted by a lubricating fluid placed in the bottom of the blister pack. The bottom portion may be spherical (c, f, g, h, l, j, k, l) or conical (a, b, d, e), and the volume of the bottom portion may be maximally equal to the remainder of the same tube (g, j) The. The opening of the blister tube package may be one to two millimeters wider than the diameter of the cylinder portion at one end of the tube near the base. This shape is in fact a cone cross section (b, e, h, k) and facilitates the gel or paste to slide out of the blister tube package. In some embodiments, the tube 15 has a narrower portion between the cylinder and base portions (i, I). This helps to separate the bolus from the lubricant if necessary. Note that the dimensions of the drawn example bubble tube package are not exactly on the right scale. As will be appreciated by those skilled in the art, all possible combinations of various features (tube length, bottom shape and volume, narrow point between cylinder and base members, cylinder wall oblique angle, edge type in tube opening) are not shown in the models described. The shape of the blister tube package as well as the smooth edge around the tube opening differs significantly from the structures of the blister packages described above. Due to the varying shape of the blister tube package, semi-solid pastabolites (e.g., compositions typically found in food products) can be readily administered.

The preferred blister tube design, which favors sliding the bolus from the blister pack, has a round, spherical bottom with a volume

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^ is the same as the remainder of the same blister pack. For example, with a bolus length of 40 mm and a diameter of 15 mm, the spherical base 30 has a radius of 12 mm (Figure 3g and 3j). This is the shape of a blister pack also gives you the opportunity to get a good grip on the blister pack.

oo Sliding is further facilitated by a model with a slightly wider opening (1-2 mm) than the diameter of the cylinder part of the blister tube package? near the bottom (Figure 3). This truncated cone shape allows only a slight forward displacement of the bolus to release most of its surface from the inner surface of the blister pack, which reduces friction at the interface between the blister and the blister pack.

In a preferred embodiment, the present invention provides tools and methods for facilitating the ingestion of solid dosage forms of pharmaceutical or nutritional products in humans by providing a semi-solid bolus material packaged in a lubricant blister tube and carrying these product forms during oral ingestion and soft contact. Similarly, oral administration of tablets and capsules to animals is assisted by the use of the present invention as applied to herbivorous and carnivorous animals according to the size of the animal. The invention also provides a new type of blister pack for a semi-solid soft bolus, which also acts as a bolus applicator directly into the mouth. In addition, a simple manufacturing process is provided to produce the entire product in an economical manner.

The method of rapidly dispensing a bolus of specific dimensions directly out of the blister tube into the mouth is based on the following factors: 1) the walls of the bottom of the blister tube are thin and flexible; 2) the size of the blister tube package is large enough to contain the desired, sufficient volume of lubricant solution at the bottom of the blister tube package; and 3) the opening of the blister pack 20 has a smooth opening that allows the blister pack to be placed in contact with the lips.

When the sealing foil is removed from the blister tube package, the solid body (e.g., tablet or capsule) is completely inserted into the tip of the gel or pastabolism. Next, the blister tube pack is lifted between the lips and the bolus is forced to slide out of the blister pack into the mouth by squeezing the bottom of the tube. When the bolus and / or lubricant gently comes into contact with the swallowing reflux trigger zone, the bolus with an immersed solid body,

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^ swallowed down throat. The process is greatly facilitated if the subject raises their chin as much as possible when pouring the oral vehicle from a blister pack into the mouth.

| In a preferred embodiment, the present invention provides an oo oral vehicle consisting of a semi-solid bolus, lubricant and flavoring and / or coloring agents packaged in a blister pack. A soft, semi-solid bolus base is capable of carrying a solid body, such as tablets and capsules, inside its tip. Bolus helps to swallow these oral dosage forms without causing any fluid or other material to become 16

As with frequent ingestion of tablets with large quantities of drinking water, there is a risk of inhalation. The relatively small amount of lubricant in the blister pack facilitates sliding of the bolus. Specific flavorings, some suitable for humans and carnivores, and others for humans and vegetarians, stimulate and facilitate oral ingestion. The beneficial microbes and plant-poorly water-soluble plant fibers that can be added to the bolus base help maintain normal gastrointestinal function.

The invention also provides a method for making blister tube packages 10, wherein the blister tube packages have a smooth edge in the opening portion (Figure 1). Such blister tube packages allow the blister tube package to come into contact with the lips without the risk of cutting the tissue with sharp edges. Preferred blister tube designs are constructed from a spherical base portion containing a lubricating fluid and a cylinder portion containing a bolus of dimensions compatible with the anatomical dimensions of the human and animal mouths and also with the size of conventional tablets and capsules (Figure 3). Further, the aperture of the cylinder member is 1 to 2 millimeters wider than the diameter of the cylinder member at a point near the bottom ball, which in effect produces a conic cross-sectional shape (Fig. 3). This further assists the bolus sliding 20 out of the blister tube pack, in which case the initial displacement of the bolus removes most of its surface from the inner surface of the blister tube pack.

The combination of various aspects of the present invention further provides a method of operating the blister tube package. One of the three key factors in this process is the thin and flexible wall of the blister tube package, which allows the bottom to be squeezed and thus forces the lubricant to move forward to push the bolus forward. Another factor is the smooth edge o around the mouth of the blister pack, which allows the blister to touch

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^ lips. The third factor is the lubricant, which causes the bolus to slide up to speed. Due to these three factors, the method facilitates the delivery of solid dosage forms of the drugs directly from the blister tube to the mouth by an effective | (Figure 4).

The present description of embodiments of the invention are provided by way of example only and are not to be construed as in any way intended to protect the invention. circle or scope.

One of ordinary skill in the art will appreciate that the scope of the present invention extends to all forms of dispersion systems suitable for the preparation of semi-solid and edible 17 boluses and all forms of boluses modified according to the examples herein to semi-solid, storage, cylindrical or quasi-cylindrical. The present invention is also not limited to the agents or mixtures of agents used to make the boluses and are illustrated in the following examples.

eXAMPLES

Example 1: Hydrophilic gel

Sodium alginate 6.0 g

Calcium Citrate 0.10 g 10 Methyl Paraben 0.15 g

Distilled water ad 100 g

Calcium citrate and methylparaben are first dissolved in 50 ml water (20 ° C). The solution is then combined with sodium alginate dispersed in 40 to 15 ml of water (20 ° C) and mixed. The viscous gels are finally adjusted to 100 g by adding water.

Example 2: Mixture of two gels

Sodium alginate 3.0 g

Calcium Citrate 0.15 g 20 Hydroxypropylmethylcellulose (K100MP) 2.0 g

Methyl paraben 0.15 g

Distilled water ad 100 g co Methyl paraben is dissolved in 50 ml water (20 ° C). Sodium alginate and calcium citrate are mixed together as dry substances and then dispersed in methylparaben solution. The hydroxypropyl methylcellulose is moistened and dispersed in 40 ml of water (50 ° C). The resulting dispersion x is then mixed with the first dispersion containing the other ingredients. The mass of the highly viscous gels obtained is adjusted to 100 g with water (20 ° C).

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Example 3: Mixture of gel with oil in water emulsion

Sodium alginate 6.0 g

Calcium citrate 0.10 g

Sunflower oil 7.5 g 5 Polysorbate 60 * 0.4 g

Methyl paraben 0.15 g

Distilled water ad 100 g * polyoxyethylene (20) sorbitan monostearate 10 Methyl paraben and calcium citrate are dissolved in 80 ml water and kept at 55 ° C. The sodium alginate is then moistened with a small amount of water and dispersed in this solution. The sunflower oil is heated to 55 ° C and mixed with polysorbate 60 and then added to the aqueous mixture containing the other ingredients and mixed thoroughly. The process was continued while adjusting the mass of the preparation to 100 g with water.

Example 4: Mixture of two gels with oil in water emulsion

Sodium alginate 4.0 g

Calcium citrate 0.15 g

Hydroxypropylmethylcellulose (K100MP) 2.0 g 20 Sunflower oil 7.5 g

Polysorbate 60 * 0.4 g

Methyl paraben 0.15 g

Distilled water ad 100 g * polyoxyethylene (20) sorbitan monostearate 25

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Dissolve the methyl paraben in 40 ml of water (55 ° C). Natriumalginaat-

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The thi and calcium citrate are mixed together as dry solids and then dispersed in the methylparaben solution. The hydroxypropyl methylcellulose is moistened with a small amount of water and then dispersed in 40 ml of water (55 ° C). Then | The two dispersions obtained are combined. The sunflower oil is heated to 55 ° C and mixed with polysorbate 60 and then added to a mixture of aqueous dispersions containing the other ingredients and thoroughly mixed. Stirring is continued while adjusting the mass of the preparation to 100 g with water.

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Example 5: Mixture of gel with water-insoluble fibers

Hydroxypropylmethylcellulose (K100MP) 2.0 g

Methyl paraben 0.15 g

Xylitol 2.0 g 5 Microcrystalline cellulose 30.0 g

Distilled water ad 100 g

Dissolve the methyl paraben in 60 ml of water and keep at 55 ° C. The hydroxypropyl methylcellulose is then moistened with a small amount of water and dispersed in this solution to give a viscous paste. Finally, the microcrystalline cellulose and xylitol are mixed with the paste and the weight of the preparation is adjusted to 100 g by addition of water.

Example 6: Mixture of gel with water-insoluble fibers

Sodium alginate 3.0 g Calcium citrate 0.05 g

Methyl paraben 0.15 g

Microcrystalline cellulose 20.0 g

Distilled water ad 100 g 20 Calcium citrate and methyl paraben are first dissolved in 30 ml water (20 ° C). The solution is then stirred and mixed with 30 ml (20 ° C) water of dispersed sodium alginate. Finally, the microcrystalline cellulose is mixed with the gel and the weight of the preparation is adjusted to 100 g by addition of water.

Example 7: Mixture of Two Gels with Water Insoluble Fibers' 25 Sodium Alginate 2.0 g 9 Calcium Citrate 0.03 g ^ Hydroxypropyl Methyl Cellulose (K100MP) 1.0 g and Methyl Paraben 0.15 g

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Microcrystalline cellulose 30.0 g cu Distilled water ad 100 g m o δ ^ Methyl paraben is dissolved in 30 ml water (20 ° C). Sodium alginate and calcium citrate are mixed together in the form of solids and then dispersed in 35 methyl paraben solutions. The hydroxypropylmethylcellulose is moistened with a small amount of water and dispersed in 30 ml of water (50 ° C). The resulting dispersion is then mixed with the first dispersion containing the ingredients other than microcrystalline cellulose. Next, the microcrystalline cellulose is added to the combined dispersions by vigorous stirring throughout the process. The mass of the resulting preparation is adjusted to 100 g with water (20 ° C).

Example 8: Mixture of Gel with Oil in Water Emulsion and Water Insoluble Fibers

Hydroxypropylmethylcellulose (K100MP) 2.0 g

Sunflower oil 7.5 g 10 Polysorbate 60 0.4 g

Methylparaben 0.15 g 3- (methylthio) propanol 0.001 g

Microcrystalline cellulose 30.0 g

Distilled water ad 100 g 15

Dissolve the methyl paraben in 50 ml of water and keep the solution at 55 ° C. The hydroxypropyl methylcellulose is then moistened with a small amount of water and dispersed in this solution. The corn oil is heated to 55 ° C and mixed with polysorbate 60 and 3- (methylthio) propanol and then added to an aqueous mixture containing ingredients other than microcrystalline cellulose and mixed thoroughly. Next, microcrystalline cellulose is added to the blended blends by thorough mixing throughout the process. The mass of the resulting preparation is adjusted to 100 g with water (55 ° C).

£ 2 25 Example 9: Mixture of gel with oil in water emulsion and water insoluble fibers i o Sodium alginate 3.0 g

Calcium citrate 0.05 g g Sunflower oil 7.5 g 30 Polysorbate 60 0.4 g

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£ 0.15 Methyl Paraben 0.15 g

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o Microcrystalline cellulose 20.0 g ° Distilled water ad 100 g 21

Methyl paraben and calcium citrate are dissolved in 50 ml water and kept at 55 ° C. The sodium alginate is then moistened with a small amount of water and dispersed in this solution. The sunflower oil is heated to 55 ° C and mixed with polysorbate 60 and then added to an aqueous mixture containing ingredients other than microcrystalline cellulose and mixed thoroughly. Next, microcrystalline cellulose is added to the blended blends by thorough mixing throughout the process. The mass of the resulting preparation is adjusted to 100 g with water (55 ° C).

Example 10: Mixture of two gels with oil-in-water emulsion and Liu-10 non-oily fibers in water

Sodium alginate 2.0 g

Calcium citrate 0.03 g

Hydroxypropylmethylcellulose (K100MP) 1.0 g

Sunflower oil 7.5 g 15 Polysorbate 60 0.4 g

Methyl paraben 0.15 g

Microcrystalline cellulose 30.0 g

Distilled water ad 100 g 20 Methyl paraben is dissolved in 25 ml water (55 ° C). Sodium alginate and calcium citrate are mixed together as dry solids and then dispersed in the methylparaben solution. The hydroxypropylmethylcellulose is moistened with a small amount of water and then dispersed in 25 ml of water (55 ° C). The two dispersions are then combined. Sunflower oil is heated to 55 ° C and mixed with polysorbate 60 and then added with aqueous dispersion

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into a mixture of ingredients other than microcrystalline cellulose ™ and thoroughly blended. Next, microcrystalline cellulose is added to the O 9 blended blends with vigorous stirring throughout the process. The mass of the resulting preparation is adjusted to 100 g with water (55 ° C).

ir 30 The boluses described in Examples 1-10 were included in the ingestion test.

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9 mm diameter round tablets were placed inside the bolus tip tray, whereby the bolus was stored in a cylindrical blister tube 12 mm in diameter and 50 mm in length. The second set of tests was run using a blister tube of the same size, but the 16mm diameter test tablet was cut in half and then inserted into the tip of the bolus.

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In both sets, the bolus was easily swallowed without the feeling that there was a tablet inside the bolus.

Example 11: Preparation of Tubes with Smooth Edges

The molds for obtaining the blister pack shape of a normal test tube are shown as an example of the thermoforming of the blister tube packages of the present invention from a plastic polymer sheet (Figure 1A). There are two techniques to make blister tube packages so that the edge of the blister opening becomes smooth. In the first technique, a separate smooth plastic ring is heat sealed to the edge of the cylindrical portion of the blister pack (Fig. 10B) after the blister pack has been cut off from the plastic sheet. In another technique, the smooth edge is formed by bending the heated plastic sheet so that the cutting point (cut by melting) is not at the edge of the blister tube package but e.g. at 20 mm (Figure 1C). This is an inexpensive model for manufacturing, while a model containing a plastic ring is more convenient to handle. The smooth edge of the Kup-15 blister pack eliminates any chance of injury to the lips when emptying the bolus blister into the mouth.

The cooled blister packs are filled with an oral vehicle of the present invention and immediately sealed with an aluminum foil or plastic film in a heat sealer. The bolus material, which has relatively poor slip properties, is packaged in blister tubes with a base for a larger volume of lubricating fluid. A packing set or collection of filled blister tubes is shown in Figure 2.

Example 12: Method of using a blister tube package

Once the barrier foil is removed from the blister pack, the tablet is completely pressurized into the tip of the gel bolus. Next, the blister pack is directed to touch the lips and the bolus is triggered to slide out of the blister into the mouth by lifting the bottom of the blister pack up (Fig. 4).

If necessary, slip is forced to occur by squeezing the bottom of the blister pack, which causes the lubricant to move and push the bolus forward-

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30 ways. When the bolus touches a specific area of the mouth, the swallowing reflex is triggered and

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A tablet buried inside a bolus is swallowed. If the patient raises their chin as much as possible, the bolus will slide and swallow without any feeling that the solid body (tablet) was swallowed simultaneously with the bolus.

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Claims (20)

Swallowing aid for solid product administration, characterized in that it comprises 5 oral vehicles comprising a) a semi-solid bolus made of a non-pourable base material which is a synthetic or natural colloidal dispersion system selected from the group consisting of gels, pastes, oil-in-water emulsions, water-in-oil emulsions, natural substances, and a mixture of two or more of such colloidal dispersions having a viscosity of the dispersion system greater than 10,000 centipoise (mPa.s) at 20 ° C as measured by Fiser, ) a non-viscous lubricating fluid surrounding the bolus, wherein the creaming fluid is a free-flowing fluid selected from the group consisting of water, vegetable oil, or oil-in-water emulsion, wherein the lubricating fluid is present in an amount of 0.05 to 100 ml, and c) the shape of the applicator container, plastic bottle or plastic tube you. Swallowing aid according to claim 1, characterized in that the dispersion system consists of separate pure ingredients, a mixture of dispersion systems, a layered dispersion system or in the form of a foam formed from two or more dispersion systems. A swallowing device according to claim 1 or 2, characterized in that the dispersion system consists of polysaccharides or other polymeric compounds including starches, vegetable gums, proteins, cellulose derivatives, carbomers, poloxamers and magnesium aluminum silicate. 4. A swallowing aid according to claim 1 or 2, characterized in that the dispersion system is a natural substance such as cooked and ground vegetables, cooked minced meat, animal fat and dairy product, or a mixture of two or more natural substances. . Swallowing aid according to claim 1, characterized in that the dispersion system is a mixture of one or more of the natural materials described in claim 4 and one or more of the pure dispersion systems described in claim 2. CVJ Swallowing aid according to any one of the preceding claims, characterized in that the bolus base material has a viscosity of 100,000 to 2,000,000 centimeters as measured by a Fibrillation Viscometer (FISER). Swallowing aids according to any one of the preceding claims, characterized in that the base material of the bolus additionally contains poorly water-soluble fibers of plant origin, synthetic fibers such as microcrystalline cellulose, useful microbes such as lactic acid bacteria, flavoring agents such as fruit. - and berry extracts and / or and synthetic compounds with the desired meat flavor, such as 3- (methylthio) propanol and 2-methyl-3-tetrahydrofurantiol, and / or sweeteners such as natural sugars and sugar alcohols, and / or power sweeteners, for example saccharin, and / or dyes such as natural or synthetic dyes. Swallowing aid according to any one of the preceding claims, characterized in that the lubricant is water, a vegetable oil with a low content (<1%) of free fatty acids such as sunflower oil, corn oil and rapeseed oil, a mixture of water with vegetable oil and an emulsifier, an oil in water emulsion, a dairy product in the form of an oil in water emulsion or a synthetic oil in water emulsion are formed. A swallowing aid according to any one of the preceding claims, characterized in that the applicator is a blister tube or sachet. A swallowing aid according to any one of the preceding claims, characterized in that the bolus is cylindrical or truncated cone-shaped, wherein the diameter of the bubble tube at the edge of the mouth is 1 to 2 mm wider than at the point near the base. Swallowing device according to one of the preceding claims, characterized in that the diameter of the cylindrical or truncated cone bolus at the edge of the mouth of the bladder tube is 6 to 12 mm for human children, 10 to 20 mm for adults, 6 to 12 mm for small pets, 10 to 20 for large pets and small pets, and 20 to 40 mm for large pets. Swallowing aid according to any one of the preceding claims, characterized in that the bolus length is 20-30 mm for human children, 30-60 mm for adults, 20-30 mm for small pets, 30-60 mm? for large pets and small domestic animals and 100-200 mm for large domestic animals. Swallowing aid according to any one of the preceding claims, characterized in that the applicator device is a bubble tube made of a polymer sheet made of polyvinyl chloride (PVC), polyethylene (PE) or polypropylene (PP), preferably polyvinyl chloride. Swallowing aid according to claim 13, characterized in that the polyvinyl chloride sheet is laminated with one or more of the following polymers: polyethylene (PE), polypropylene (PP), polychlorotrifluoroethylene (PCTFE), cyclic olefin copolymers (COC), cyclic olefins (COP) ) and glycol-modified polyethylene terephthalate. Swallowing aid according to claim 13 or 14, characterized in that the thickness of the PVC layer is between 0.15 and 0.30 mm and the thickness of the laminate (s) is between 0.015 and 0.100 mm. Swallowing aid according to any one of the preceding claims, characterized in that the bladder tube is cylindrical or cut cone-shaped, wherein the diameter at the edge of the opening is 1 to 2 mm wider than at the base and a conical or spherical base for the lubricant. Swallowing aid according to Claim 16, characterized in that the volume of the spherical bottom is at most equal to the volume of the remainder of the same bubble tube and the length of the bubble tube is 10 to 30 mm longer than the bolus lengths given in claim 12. Swallowing aid according to Claim 9, characterized in that the applicator is a sachet made of aluminum foil or liquid-resistant carton laminated with one or more of the following polymers: PE, PP, PCTFE, COC, COP and glycol modified polyethylene terephthalate. . Swallowing device according to claim 18, characterized in that the cross-section of the sachet has the following geometry: triangle, square, pentagon, hexagon, hexagon and octagon, and the base 30 is flat. Use of a swallowing aid according to any one of the preceding claims for the administration of solid forms of pharmaceutical and nutritional products. CVJ m o δ CVJ