CN1336820A - Method for producing film-type dosage forms - Google Patents

Abstract

A process for the production of sheet-like administration forms by way of coating and drying a solvent-containing, spreadable mass on a substrate is characterized in that the drying takes place in a first drying stage at between 30 and 50 DEG C, in a second drying stage at between 35 and 80 DEG C, and in third drying stage at between 25 and 50 DEG C.

Description

Make the method for film-type dosage forms

The present invention relates to a kind of film-type dosage forms, it is used to make up, the product of medicine or food technology.

The flat administration form has been known the mucosa that is used for zone, oral cavity and mouth.Therefore, United States Patent (USP) 3 444 858[Lip river ropes (Russell), 1969] tablet based on gelatin class material described.

In European patent 0 216 762, the water-soluble film of starch, gelatin, glycerol or Sorbitol is disclosed, it uses the method for roller coating to apply.This document is mentioned in this content simply: the also available chemical reagent of this dosage form, spice and analog are made.

In European patent 0 460 588, the prescription that is suitable for making laminar system is in principle disclosed.At this, constituent has the film former of 20 to 60 percentage by weights, the gelatinizing agent of 2 to 40 percentage by weights, the active substance (being flavoring agent at this) of 0.1 to 35 percentage by weight and the inertia implant of maximum 40 percentage by weights, and it is considered to provide special advantage.

Deutsche Bundespatent 36 30 603 is seen the special advantage that goes up design flat dosage form at carrier mass (disengaging thin film), makes on dosage divisible.

United States Patent (USP) 4 128 445 and 4 197 289[Si Turen can lattice (Sturzenegger), 1978] propose to come the relevant possible technology solution of load with active substance.

For the lamellar system of pastille, water expanding layer and water-fast barrier coagulate the double-layer structure of thin film, also are considered to favourable (United States Patent (USP) 5 047 244).

In the manufacturing of this type of thin film, some hydrophilic films form thing, particularly amylopectin (pullulan) and other glucosan and cellulose derivative, show moistening inadequately on general coated media.This can cause too early or difficult substrate to be separated, and causes uneven film thickness.As the method for remedying, the use of United States Patent (USP) 4 562 020 suggestion substrate circulates into a loop during the course, this substrate is based on nonpolar heat stability polymer, and in manufacture process, make it stand the Corona discharge Treatment on surface continuously, thereby new polar surfaces is provided regularly, and it has enough safe wetting powers.Baking temperature is 40-110 ℃; The temperature of mentioning in an embodiment is 60 ℃ and 85 ℃.

The fragrance thin film that produces on pure film matrix has proved imperfect, because it all is slick on the two sides.This product is to reprocessing and with the stacked use that the thin film cutting forms, only having the limited suitability.The diaphragm that this is stacked or the diaphragm of perforation often are to offer client with suitable agent shape dispersant, can trend towards mutual bonding, and it makes that to remove this tablet safely more much more difficult.This laminar administration form, because the small weight of its per unit area (generally being about 10-80 to restrain/every square metre), and the trend static electrification that becomes, and at the same time, because in order to quicken removing of the latter, its surface is designed to slide over each other, and this viewpoint not only interferes with use, has also disturbed process technology.

The 3rd demand that must reach with this method is: avoid providing maximum processing speed simultaneously because heat is scattered and disappeared fragrance.Prior art and end demonstrate data to point out the solution to this demand.

Still keep the demand that the end solves in the prior art by these, cause purpose of the present invention to be: the method for making laminar active ingredient carriers is provided, it can have accurate and reproducible coating quality, avoid the thin film of final generation in the stacked thing or the mutual adhesion of tablet of thin slice, and avoid simultaneously polluting and excessive heat load, obtain and make speed with height.

To reach this purpose according to of the present invention, be wherein continuous at once with hydrophilic polymer solution and added the coating of active substance, and extra auxiliary substance, the air flow of thermophilic (30-50 ℃) are passed through on this material, temperature rises (30-80 ℃) a little afterwards, follow-up re-adjustment phase with 25-50 ℃.This process rate is adjusted primely, makes relative soil humidity (suitable humidity or suitable air humidity) all keep the relative humidity of 50-75% in all cases, is preferably the relative humidity of 60-68%.By using the substrate of rough surface, be preferably thermoplastic polypropylene, polyethylene, polyethylene terephthalate, Merlon, and the thin slice of these polymer, the paper that especially preferably has polyethylene coating, it is avoided effectively in stacked thing, the mutual adhesion of the diaphragm of Zhi Zaoing afterwards.

Method of the present invention can be applicable on any type of flat product, for example: as food, medicine or cosmetics, it can produce in coating procedure by by solvent, particularly water, come fluidised agglomerate, and comprise solid, hydrophilic alkaline matter and other optional component.

These hydrophilic alkaline matters can be polymer, and for example: starch and derivant thereof, agar, gelatin, cellulose and cellulosic derivant, alginic acid, gala glucomannan (galactoglucomannan), antler glue and other are allowed and be used for vegetable glue, amylopectin (pullulan) and other glucosan (glucans, dextrane) and polyvinyl pyrrolidone, polyvinyl alcohol or polyacrylic acid homopolymer and the copolymer that use in each field.Used polyvinyl alcohol is advantageously by the form of partial hydrolysis, and wherein 1 to 20% and especially preferably about 12% hydroxyl is replaced by acetyl group.

The method according to this invention is effective especially to the problem agglomerate that contains a high proportion of amylopectin (pullulan), antler glue or cellulose esters.

The hydrophilic additive that also can use small-molecular weight is as the reagent that forms structure; These are most of with the affected purpose that reaches application-specific.Possible additive is substituent, organic acid, the Polyethylene Glycol of sugar, sugar alcohols, sugar particularly.

Because its bad dissolubility also can be included in and not form the mixture of molecular dispersion or the solid matter of solution in the alkaline matter.Suitable material for example is: the carbonates of alkaline-earth metal, phosphoric acid ester, silicates or Sulfates, zinc oxide, titanium oxide or other colorant, Talcum, lactose, cyclodextrin or starch and starch derivatives, as long as it forms its own solid dispersed phase in end product.

Above-mentioned enumerating just for example, and material that can identical function well known by persons skilled in the art is finished.

For example, active component can be the active agent of medicine or cosmetic, diet additive, colorant or the diagnostic agent of food.Especially, method of the present invention can be used with flavoring agent, otherwise this flavoring agent is difficult to processing because of its volatility.But the flavoring agent that the present invention uses is mainly the volatile flavor compounds that necessary oils and fats (volatility of the flavor component of plant, water-insoluble distillation) and other and glassware for drinking water have limited mutual solubility.Like the new fresh seasoning of Oleum menthae, comprise in flavouring agent (fragrant peppery aromatic series) edible, in normal-butyl titanium or eucalyptol, the example is a phenylethanol, composition as aromatic series, Mentholum, eucalyptole (eucalyptol), CAM and the pinene of rose scent, and the flavouring agent with medical usage, for example: Eucalyptus oil, thyme oil, methyl salicylate, terpene oil (terpentine oil) and chamomile oil.

This is essentially a very wide spectrum, and aromatic series has been used in the additive of food, and is in ready-formed food additive.These example is so-called fruit ethers, but other aromatic series is also arranged, for example: ethyl vanillin, 6-Methylcoumarin, citronella oil or Nomal Butyl acetate.The additive of surfactant can improve the dispersing uniformity that fragrance drips.Under specific situation, it is provable to be favourable to the identical or different constituent that is used in one or more layer, for example, can obtain specific surface or tensile properties.

For example, agglomerate be solvent (generally be water, and for example can use: ethanol, acetone and other compatible, physiologically acceptable solvent and composition thereof) in solid constituent is sprinkled into, rubs or slowly dissolve and makes.Provide as prescription, add the flavoring agent of weighing in advance and other liquid state, lipophilic additive in mutually, stir lentamente simultaneously at this.

Be concerned about with regard to purpose of the present invention, before applying, with the high speed homogenizer for even composition with this agglomerate of homogeneous phase, become great advantage.

The method according to this invention, the agglomerate that is coated on the substrate is to use the method for smearing coating, scraper coating or extruding, and dry in by the dry road of at least three independent temperature control areas.

This material can comprise the known and widely used material of those skilled in the art and constitutes in principle, as PETP, polyethylene, polypropylene, Merlon, polyurethane.The thin slice that also can use these materials and other polymer, paper, glass fibre and form other material of structure increases tensile strength.Use as silication in order to regulate the cohesiveness on surface, can to weigh, fluoridize, acid treatment or sided corona treatment, but under each individual cases, these need clarify its physiology tolerances to the application target of being correlated with.

Do not have level and smooth profile if apply the surface that agglomerate faces, but profile is not sharp, and when under any circumstance being the profile of rough surface, can reaches special advantage according to the present invention.Spike is 0.1 micron to about 10 microns to the height of trench, is preferably 0.5 to 3 micron.Its advantage is to be the grand outthrust of circle in micro structure, and it further reduces sliding friction.

The objective of the invention is to want to reach: wherein exsiccant is to cause under the processing temperature of intensification regularly, and in the end zone, final time descend 10 ℃ then.Advantageously, but adjustment process speed makes to obtain having the product that to be equivalent to humidity be the 50-75% relative humidity, be preferably the 60-68% relative humidity.Obtaining under these process conditions of product, proving surface-stable, flexible and anti-fracture, and anti tear widely.In fact the surface of gained shows does not have " cold flow (cold flow) ", and is that directivity is stable basically therefore.Can remove this thin film from supporter, and the elongation that does not perceive takes place, and can further process respectively.

The measurement of impartial air humidity is as follows: use rubber gloves, the product sheet of the coming of new that at once and apace folding area is about 0.1 square metre, and be placed in the wide-mouth glass container, its lid provides a perforate, makes hygroscopic gage outfit be imported into wherein.After about 1 minute, the structure of view apparatus and deciding reads measured value.

After vertically, further process, on device, burrow, or carry out in the horizontal simply.The sheet products that is produced preferably has thickness 20-300 micron; Advantageously from 0.5 to 12 square centimeter of its big I.Follow-up packing can be carried out independent or stackedly, for example pouch or the dosage packing to encapsulate.

Claims (7)

1. A method for producing a flake-like application form by coating and drying a solvent-containing extensible mass on a substrate, characterized in that, in a first drying stage, the drying is carried out at between 30 and 50°C, in the second drying stage between 35 and 80°C, and in the third drying stage between 25 and 50°C. 2. A method according to claim 1, characterized in that the process rate is adjusted so as to maintain a relative substrate humidity of 50-75% relative humidity, preferably 60-68% relative humidity. 3. Method according to one or more of the preceding claims, characterized in that the flaked product contains flavoring agents. 4. The method according to one or more of the preceding claims, characterized in that the flaked product comprises pullulan as main constituent. 5. Method according to one or more of the preceding claims, characterized in that the flakes are dried at a drying temperature of 30 to 50°C in the first third of the drying stage and in the second third The drying temperature is from 35 to 80°C in one of the drying stages and from 25 to 50°C in the last third of the drying stage. 6. Method according to one or more of the preceding claims, characterized in that the drying of the flake-shaped product is carried out on a material with a rough surface. 7. A method according to claim 6, characterized in that polyethylene-coated paper is used as material with a rough surface.