WO2000047190A2 - Method for producing film-type dosage forms - Google Patents

Abstract

The invention relates to a method for producing film-type dosage forms by applying a coating of a spreadable mass containing a solvent on a substrate and drying. The invention is characterised in that the drying process is carried out in a first drying phase between 30 and 50 °C, in a second drying phase between 35 and 80 °C and in a third drying phase between 25 and 50 °C.

Description

Process for the production of film-like dosage forms

The present invention relates to film-like dosage forms for use as cosmetic, pharmaceutical or food products.

Flat dosage forms to be used in the mouth area and on the mucous membranes of the mouth are known. No. 3,444,858 (Russell, 1969) already describes medicament strips based on a gelatin-like material.

EP 0 216 762 presents a water-soluble film made of starch, gelatin, glycerin or sorbitol, which is coated by means of a roller application process. It is mentioned briefly that such dosage forms can also be produced for chemical reagents, flavorings and the like.

A formulation that is fundamentally suitable for the production of film-shaped systems is presented in EP 0 460 588. Here, particular advantages are seen in the composition of 20 to 60 percent by weight film former, 2 to 40% gel former, 0.1 to 35 percent by weight of active ingredient (here: flavoring) and a maximum of 40 percent by weight of an inert filler.

DE 36 30 603 sees particular advantages in designing the flat dosage form on a carrier material (separating film) in a dose-wise manner.

US 4 128 445 and 4 197 289 (Sturzenegger, 1978) deal with possible technical solutions when loading with active substances. For drug-containing film-shaped systems, advantages are also seen in a two-layer structure consisting of a water-swellable layer and a water-insoluble barrier film (US Pat. No. 5,047,244).

Some hydrophilic film formers, in particular pullulan and other glucans, but also cellulose derivatives, have inadequate wetting on conventional coating media in the production of such films. The consequence can be premature or difficult substrate detachment and uneven resulting film thickness. To remedy this, US Pat. No. 4,562,020 recommends the use of a substrate rotating in the process as a loop on the basis of non-polar, heat-stable polymers, which is constantly subjected to a surface corona treatment during the process and thus constantly receives a sufficiently securely wetting, polar surface. It works at drying temperatures between 40 and 110 ° C; In the examples there are temperatures between 60 and 85 ° C.

The aroma films produced on the described pure film substrates prove to be disadvantageous because of their smoothness on both sides. Such products are only of limited suitability for further processing and use in stacks formed by foil cutting. Such stacks of pieces of film or die cuts, as are often offered in suitable dosing dispensers for use by the consumer, tend to stick to one another, which makes safe removal very difficult. Since such film-like dosage forms tend to be statically charged due to their low basis weight (typically approx. 10 to 80 g / m ² ) and the surfaces are designed to be displaceable relative to one another because of the later easier removal, this aspect is not only in use but also in the process technology disruptive. A third requirement for the process is the avoidance of heat-related loss of aroma at maximum process speed, for which there are no indications from the prior art either.

From these requirements which have not yet been solved in the prior art, the object of this invention is to provide processes for the production of sheet-like active substance carriers which enable an exact and reproducible coating quality, prevent the finally produced film pieces from adhering to one another in the stack and avoid contamination and too high heat loads are available at high process speeds.

The object is achieved according to the present invention in that the coating of the solution of hydrophilic polymers with added active ingredients and other auxiliaries is immediately followed by an overflow of moderately warm (30-50 ° C.) air, then the temperature is slightly increased (35 -80 ° C), followed by a reconditioning phase at 25-50 ° C. The process speed is advantageously regulated in such a way that a relative substrate moisture (equivalent moisture or equivalent air humidity) of 50-75% RH, preferably 60-68% RH, is not left in any case.

By using substrates with a rough surface, preferably thermoplastics made of polypropylene, polyethylene, polyethylene terephthalate, polycarbonate and laminates of these polymers, particularly preferably polyethylene-coated paper, sticking of the individual film pieces produced later is effectively avoided in the stack.

The method according to the invention can be applied to any form of sheet-like products, for example for use as food, pharmaceuticals or cosmetics, which in a coating process consist of a solvent, in particular re water, liquefied mass, which contains solid, hydrophilic raw materials and optionally further components, can be produced.

These hydrophilic raw materials can include polymers such as starch and their derivatives, agar-agar, gelatin, cellulose and cellulose derivatives, alginic acid, galactomannan, carrageenan, other vegetable gums permissible for the respective field of application, pullulan and other glucans, dextran, polyvinylpyrrolidone, Polyvinyl alcohol or polyacrylic acid ho o and copolymers. The polyvinyl alcohol used is advantageously a partially hydrodysed form in which between 1 and 20%, particularly preferably approximately 12%, of the hydroxyl groups are replaced by acetyl groups.

The method according to the invention has an effect in particular in the case of problematic compositions which contain high proportions of pullulan, carrageenan or cellulose esters.

Hydrophilic additives of low molecular weight can also be used as structure formers; they mostly meet application-specific goals. Here come Sugar, sugar alcohols, sugar substitutes, organic acids, polyethylene glycol in question.

It can also contain solid substances that do not form a molecularly disperse mixture or solution in the base material due to their low solubility. Suitable substances are, for example, carbonates, phosphates, silicates, or sulfates of alkaline earth metals, zinc oxide, titanium dioxide or other color pigments, talc, lactose, cyclodextrins or starch and starch derivatives, provided that they form their own, solid, disperse phase in the end product.

The above list is exemplary and can be supplemented by substances of the same function known to the person skilled in the art. Active components can be, for example, medicinal or cosmetic active ingredients, dietary additives to foods, dyes or diagnostics. In particular, the process according to the invention is applicable to the aroma substances which are otherwise difficult to process because of their volatility. Aromas which can be used with this invention are essentially essential oils (volatile, water-insoluble distillates from fragrant plant components) and other volatile, fragrant substances which have a limited miscibility with water. Examples include, for example, phenylethanol as a component of rose fragrances, menthol, eucalyptol (cineol), camphene and pinene in peppermint-like aromas, appetizing aroma substances (spice aromas) such as n-butyl phthalide or cineol, but also aroma substances with medicinal use such as eucalyptus - And called thyme oil, methyl salicylate, turpentine oil and chamomile oil.

Essences and flavors, which are used as additives for food and in pre-made food additives, occupy a very wide field. The so-called fruit ethers may be mentioned here by way of example, but also other flavorings such as ethylvanillin, 6-methylcoumarin, citronellol or also n-butyl acetate. Additions of surface-active substances can improve the uniformity of the distribution of aromatic droplets.

In special cases it can prove to be advantageous to apply one or more further layers of the same or different composition, for example in order to achieve special surface or tensile properties.

The mass is obtained, for example, by sprinkling, kneading or slowly digesting the solid components in the solvent (usually water, but also, for example, ethanol, Acetone and other compatible, physiologically acceptable solvents and their mixtures are used). If contained in the recipe, the pre-weighed amount of flavoring and other liquid, lipophilic additives are added to this phase with slow stirring. In the interest of the objective of the invention, it has proven to be very advantageous with regard to a more uniform nature to homogenize the mass before coating via a high-speed homogenizer.

In the process according to the invention, the mass is coated onto a substrate by brushing, knife coating or extrusion processes and is dried in a drying channel consisting of at least three independently temperature-controlled zones. The substrate can in principle be made from substrates known to those skilled in the art and widely used, e.g. Polyethylene terephthalate, polyethylene, polypropylene, polycarbonate, polyurethane exist. Laminates of these materials with other polymers, paper, glass fibers and other structure formers are also used to increase the tear resistance. Measures such as siliconization, fluorination, acid treatment or corona treatment can be useful to regulate the surface adhesion, but in individual cases they need to be clarified as to their physiological compatibility for the respective application.

Particular advantages according to the invention are achieved if the surface facing the coating composition does not have a smooth, but rather a contoured, matted, in any case rough surface contour. The roughness can be in the range from 0.1 µm to approximately 10 µm, preferably between 0.5 and 3 µm. Rounded elevations, which further reduce sliding friction, are advantageous in the microscopic fine structure.

The aim of the invention is regularly achieved when the drying with initially increasing, at the latest in in the last zone then process temperature reduced by 10 ° C again.

The process speed is advantageously set so that a product with an equivalent air humidity of 50-75% RH, preferably 60-68% RH, is obtained.

Under these process conditions, the products obtained proved to be surface-stable, flexible and unbreakable and largely tear-resistant. The resulting surfaces have practically no "cold flow", so they are basically dimensionally stable. The film can be removed from the base without noticeable stretching and processed separately.

The equivalent air humidity is determined as follows: A freshly manufactured product strip of approx. 0.1 m ^a surface is quickly folded with rubber gloves and placed in a wide-necked glass vessel, the lid of which is drilled so that the measuring head of a hygrometer is inserted becomes. After approximately one minute, depending on the type of device, the measured value can be read off.

Further processing takes place after a longitudinal cut in punching devices or simply through a cross section. The film-shaped products produced preferably have a thickness between 20 and 300 μm; their size can advantageously be 0.5 to 12 cm ² . The subsequent packaging can be done individually or in a stack, for example in sealed bags or dispensers.

Claims

EXPECTATIONS

1. A process for the production of film-like dosage forms by coating and drying a solvent-containing, spreadable composition on a substrate, characterized in that the drying in a first drying phase between 30 and 50 ° C, in a second drying phase between 35 and 80 ° C and in a third drying phase between 25 and 50 ° C.

2. The method according to claim 1, characterized in that the process speed is regulated so that a relative substrate moisture of 50-75% RH, preferably 60-68% RH, is not left.

3. The method according to one or more of the preceding claims, characterized in that the film-shaped product contains flavorings.

4. The method according to one or more of the preceding claims, characterized in that the film-shaped product contains pullulan as the main component.

5. The method according to one or more of the preceding claims, characterized in that the drying of the laminate in the first third of the drying phase between 30 and 50 ° C, in the second third between 35 and 80 ° C and in the last third between 25 and 50 ° C lies.

6. The method according to one or more of the preceding claims, characterized in that the drying of the film-shaped product takes place on a surface-rough material.

7. The method according to claim 6, characterized in that a polyethylene-coated paper is used as the surface-rough material.