The method of manufacture of dosage forms in the form of sheets

 

(57) Abstract:

The invention relates to cosmetic, pharmaceutical and food industries. Perform drawing on a substrate and drying, solvent-dispersed mass. At the first stage of drying is carried out at a temperature in the range from 30 to 50C, on the second stage at a temperature in the range from 35 to 80 C and at the third step at a temperature in the range from 25 to 50C. The process regulate to obtain a product with a relative humidity of 50-75%. The invention allows to prevent sticking of the finished products. 4 C.p. f-crystals.

The invention relates to dosage forms in the form of sheets, cosmetic, pharmaceutical products and past technological processing of food.

Known flat dosage forms used orally and on the mucous membranes of the oral cavity. Thus, in U.S. patent 3444858 (issued in the name of Russell, 1969) described the strips on the basis of gelatin containing a drug.

In the European patent EP 0216762 disclosed water-soluble film of starch, gelatin, glycerol or sorbitol, which is applied to the floor using a roller. In this regard, in the above-mentioned patent briefly mentions that such P CLASS="ptx2">

Composition, fundamentally suitable for the manufacture of flat systems, disclosed in European patent EP 0460588. A particularly preferred composition includes from 20 to 60 wt.% film-forming means, from 2 to 40 wt.% gel-forming means, from 0.1 to 35 wt.% active ingredient (in this case odorants) and not more than 40 wt.% inert filler.

In the Federal Republic of Germany patent DE 3630603 as specifically disclosed preferred flat dosage form based media (release film), is able to pull away, releasing separate doses.

In U.S. patent 4128445 and 4197289 (issued in the name Sturzenegger, 1978) revealed the possible technical solutions related to the load of active substances.

For containing medicines systems in the form of sheets as the preferred also considered two-layer structure consisting of swelling in water layer and the water-insoluble barrier film (U.S. patent 5047244).

In the manufacture of such films some hydrophilic film-forming means, in particular, pullulan and other glucans and cellulose derivatives do not provide sufficient moisture conventional coating materials. This can lead to premature or see problems in U.S. patent 4562020 it is recommended to use a substrate, circulating in the manufacturing process in a closed loop. In this case, the substrate based on thermostable non-polar polymers, and in the process of making it continuously exposed to corona discharge, which constantly provides a new polarity of its surface, which has a fairly reliable moisturizing ability. Drying is carried out at a temperature in the range from 40 to 110S; examples are temperature 60 and 85C.

Aromatic film produced on the substrate of the thin film, have proven to negatively because they are smooth on both sides. These products are only partly suitable for further processing and use in the footsteps generated during the cutting of the film. These foot pieces of film or pieces of the perforated tape, which often offer the consumer the appropriate tools dosages, tend to stick together, which makes it difficult reliable detaching pieces of film from each other. As such dosage forms in the form of a film due to its low specific weight per unit area (usually in the range 10-80 g/m2) is prone to static charge, and to facilitate subsequent UD is the STATCOM not only during use, but also in the manufacturing process.

The third condition to be met by the way, is to prevent the loss of aromatic properties under the influence of heat while providing maximum performance. In known from engineering methods do not contain any information about the solution of this problem.

Given such requirements, to the present time are not made known in their techniques, the methods, the aim of the present invention is to provide methods of manufacturing a flat carriers of active ingredients, providing a precise and reproducible quality coating that prevents sticking to each other finished products made from pieces of film or sheet in the foot and provide high performance without pollution and excessive heat load.

This objective is achieved in accordance with the invention due to the fact that directly after the coating of the active ingredients and auxiliary substances in a solution of hydrophilic polymer through a substance flow stream moderately warm air (30-50C), and then only slightly (up to 35-80C) increase the temperature and, finally, euxesta thus, the relative humidity of the substrate (equivalent to the humidity or equivalent humidity) in any case maintained at 50-75% relative humidity, preferably, 60-68% relative humidity.

Through the use of substrates with a rough surface, preferably thermoplastics polipropilene, polyethylene, polyethylene terephthalate, polycarbonate and laminated materials based on polymers, particularly preferably polyethylene coated paper effectively prevented from sticking to each other subsequently made of separate pieces of film placed in the foot.

The method according to the invention is applicable in respect of any products, having a flat shape, such as food, medicines or cosmetic products, which may be in the process of coating made from a mass of fluidized by means of solvents, especially water, and containing solid hydrophilic initial substance and optional additional components.

Data hydrophilic source materials can be polymers, such as starch and its derivatives, agar-agar, gelatin, cellulose and derivatives of cellulose which corresponds to the region, pullulan and other glucan, dextran, polyvinylpyrrolidone, polyvinyl alcohol homopolymers and copolymers of polyacrylic acid. Polyvinyl alcohol is used preferably in a partially gidrolizovannogo, from 1 to 20%, particularly preferably about 12% of its hydroxyl groups replaced by acetyl groups.

The method according to the invention, particularly effective when using materials with a high content of pullulan, Cartagena or cellulose ethers.

As structuring tools can also be used hydrophilic additives of low molecular weight, which serve mainly to achieve a specific purpose. Possible additives, among others, are sugar, sugar alcohols, sweeteners, organic acids, polyethylene glycol.

Can also be used solids, due to their low solubility of not forming a molecular-disperse mixture or solution in substance basis. Can be used, for example, substances such as carbonates, phosphates, silicates or sulfates of alkaline earth metals, zinc oxide titanium oxide or other color pigments, talc, lactose, cyclodextrins or starch e above list is only exemplary and may be supplemented by substances with similar action known to specialists in this field of technology.

Existing components can be, for example, medical or cosmetic active remedies, dietary supplements, dyes, or diagnostic tools. In particular, the method according to the invention can be applied to aromatic funds, labor recycle in other ways because of their volatility. Aromatic agents that can be used in this invention are mainly essential oils (volatile, water-insoluble distillate aromatic constituents of plants) and other volatile aromatic substances, in a small degree miscible with water. Their examples include phenylethanol component of the scent of roses, menthol, eucalyptol (cineole), camphene and pinene contained in the aromatic substances with the smell of peppermint, aromatic substances, stimulating appetite (spicy fragrant substances), such as, for example, n-butylphthalide or cineole, but also aromatic substances for medical purposes, such as eucalyptus oil, thyme oil, methyl salicylate, terpentine oil and chamomile oil.

As food additives and additives to food semi-finished products using a large number of essential and aromaticheskiye, as ethylvanillin, 6-methylcoumarin, citronellol or n-butyl acetate. By adding surface-active substances it is possible to improve the uniformity of distribution of small droplets of aromatic substances. In special cases it is preferable to apply one or more additional layers of the same or a different composition to obtain the surface, for example, with the special properties of surface tension.

Mass produced, for example, by adding, mixing or slow cooking of the solid components in the solvent (usually water, but also, for example, ethanol, acetone or other compatible physiologically acceptable solvents and their mixtures). At this stage in the process of slow stirring a predetermined number of aromatic agents and other liquids, lipophilic additives in accordance with the recipe.

To achieve the objectives of the invention in that, as to ensure homogeneity of the composition, particularly preferably before applying the mass to the substrate homogenize its high-speed homogenizer.

In the method according to the invention the weight applied to the substrate by the method of dispersion, using a knife device or method extrusi olivetta independently.

The substrate can, in principle, consist of well-known specialists in the art and widely used materials, such as, in particular, polyethylene terephthalate, polyethylene, polypropylene, polycarbonate, polyurethane. To increase the tensile strength of these materials is also used in the form of laminates in combination with other polymers, paper, glass and other structural materials. To adjust the adhesive ability of the surface it is recommended to carry out such operations as siliconefree, fluoridation, acid treatment and treatment by corona discharge, however, for this it is necessary to clarify the physiological compatibility of the application of such measures in each individual case.

Particularly preferred according to the invention, if the surface facing the coating material is not smooth, but rough, matte, and in any case has irregularities. The height of such irregularities may be in the range from 0.1 to about 10 microns, preferably between 0.5 and 3 microns. Preferred are rounded protrusions in the microstructure, further reducing the sliding friction.

The purpose of the invention is usually achieved if the% is b, the method preferably regulate so in order to obtain products with a moisture content equivalent to 50-75% relative humidity, preferably, 60-68% relative humidity. Under such technological conditions provides surface stability, flexibility and tensile strength, and high resistance to tearing of the finished product. The resulting surface is practically not deformed in a cold state, and thus differ predominantly dimensional stability. The film can be removed from the substrate without appreciable stretching in length and can be separately subjected to additional processing.

Equivalent humidity is determined as follows: just made a strip product with an area of about 0.1 m2immediately and quickly bend, using rubber gloves, and placed in a glass vessel with a wide mouth, the lid is done through hole for the measuring head gyroscope. After about one minute, depending on the design of the device, receive the measured value.

After cutting on the longitudinal segments perform additional processing on the perforators or simply cross cutting devices. Products in the form of sheets, the preference is UP>2. They are then packaged or placed in a foot, for example, in airtight bags or metering dispensing device.

1. The method of manufacture of dosage forms in the form of sheets by applying on a substrate and drying the solvent-dispersed mass, characterized in that the drying of the applied mass during the first third of the stage drying is carried out at 30 - 50C, during the second third at 35 - 80C and the last third at 25 - 50C, and the drying process is adjusted so as to obtain a product with a relative humidity of 50-75%, preferably 60-68%.

2. The method according to p. 1, characterized in that the product is in the form of a sheet fragrance.

3. The method according to p. 1 or 2, characterized in that the product is in the form of a sheet contains pullulan as hydrophilic educt.

4. The method according to one or more of the preceding items, characterized in that the drying of the product in the form of a sheet carried out on a substrate with a rough surface.

5. The method according to p. 4, characterized in that the substrate with a rough surface using paper coated with polyethylene.

 

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