JPS6028810B2 - Manufacturing method of pharmaceutical oil - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of pharmaceutical foils containing active substances as pharmaceutically active ingredients for application internally and externally to the body.

BACKGROUND OF THE INVENTION From Belgian Patent Specification No. 637363, a paper film suitable for oral administration coated with an active substance is known.

The film consists of water-bathable cellulose fibers and a water-soluble binder. Sodium carboxymethyl cellulose is preferably used as water-lacquer binder. The active ingredient is brought onto the paper foil by dropping the dissolved active ingredient, by sprinkling the solid active ingredient or by passing the foil through the active ingredient solution. This method has the disadvantage that the production of the film and the incorporation of the active substance are discontinuous steps and that the dosing accuracy, which is very important in the case of today's low active substance doses, is not very good. This inaccuracy arises not only when the active substance is applied to the carrier, but also in the manufacture and pretreatment of the carrier, and also due to changes in the carrier material during storage. For example, it has been found that the method of the above-mentioned Belgian patent does not produce a uniform film layer when a film former is used, and that the film shrinks during drying. It is easy to understand that if the carrier is not uniform, the acceptance of the active substance will also not be uniform.
Furthermore, the active substance that is only deposited on the surface can partially separate again during handling of the foil, for example during packaging. The sodium carboxymethylcellulose used as a binder begins to dissolve in the stomach, liberating carboxymethylcellulose in the process. The carboxymethylcellulose partially encapsulates the active substance and releases it slowly or not at all. It has now been found, however, that when producing foils incorporating active substances and using film-forming agents soluble in water or organic solvents, it is possible to obtain films of uniform thickness and uniform distribution of the active substances. .

Preference is given to suitable film-forming agents which are soluble both in water and in organic solvents. Examples of the film forming agent include poly-N-vinylpyrrolidone, vinylpyrrolidone-vinyl acetate,
Methyl- and ethylcelluloses, preferably nonionic, water-dropping hydroxyalkyl ethers of cellulose, such as hydroxypropylcellulose, hydroxyethylcellulose and methylhydroxyph.

This applies to lopylcellulose. Fillers and active substances and preferably small amounts of release agents can be added to the film-forming agent. Suitable release agents are inter alia polyoxyethylene polyoxypropylene polymers (Pluronik (PL)).
URONIC) F68®, PoIJ oxylstearate, alkyl- or acyl-substituted polyaddition products of ethylene oxide, such as CREMOPHO
R) EL (registered trademark), silicone and silicone emulsion, glycerin, propylene glycol and metal soap. Suitable fillers are, for example, cellulose, sugars such as lactose, dextrose, rice bran, etc., starches, polyhydric alcohols such as mannite, calcium carbonate, calcium phosphate, talc and colorants in soluble form or as pigments.

The filler can be partially or completely relayered with active substances. If soluble fillers or active substances are used, transparent, smooth films are formed; if insoluble fillers or active substances are used, white or colored paper-like films are formed. Ru. The invention can be applied to all agents used in human and veterinary medicine.

Oral administration is particularly relevant for applications within the body. External application is in particular topical application on the skin and into body cavities, such as the nose, ears, genital cavities, etc. Agents include, for example, gestagens, estrogens, mixtures of gestagens and astrogens, tranquilizers, antidiabetics, sulfonamides, antibiotics, antitrichomonads, anti-inflammatory agents such as corticoids, and the like. The pharmaceutical agent can be present in solution or homogeneously suspended in the carrier material.

The active substance content in the film can be approximately 0-60%. As unit dosage forms, small pieces are usually cut or punched out containing the active substance in amounts that are also contained in tablets, sugar-coated tablets, ointments, suppositories and the like. Thus, the amount of active substance per unit dose can be arbitrary depending on the type of application and is between about 1 and 0.5 hours, although it can also be slightly lower or lower than that range. It is also, of course, possible to produce carriers (placebos) that do not contain the active substance. In order to produce a medicament in the form of a film according to the invention, the active substance and/or the release agent are not dissolved but are now suspended, a film-forming agent and optionally a filler are added, optionally homogenized, and the solution is then suspended. The suspension is now applied in the form of a film onto a film forming machine.

The film obtained by drying the same coating is divided into pieces (units) of arbitrary size. In the above solution or suspension, the film forming agent is present in an amount of about 6 to 20% by weight, the filler is in an amount of about 0 to 30% by weight and the release agent is preferably 0.01 to 2%.
is mixed in by weight. Solvents and suspending agents are 48-84
% (W/W) and consists of water and/or one or more organic solvents.

Suitable organic solvents are physiologically harmless solvents or solvents that can be removed by drying until only a physiologically harmless residue remains. Such solvents include, for example, ethyl alcohol,
Isopropanol, methylene chloride, etc. and mixtures thereof. Water and ethyl alcohol or a mixture of water and ethyl alcohol are preferably used. The layer thickness of the wet application is approximately 0.1-2 mm, that of the dry film approximately 0.1-2 mm.
0.05 to 1 rib, advantageously 0.07 to 0.3 willow.

Processes for producing medicaments in film form in one working step (continuous process) have the advantage that the active substance is homogeneously and evenly distributed in the active substance carrier.

Depending on the concentration of active substance in the carrier, the thickness of the film and the area of the film, it is possible to vary the unit dosage very easily. It is also possible to produce foils with applications containing different active substances and/or different active substance concentrations adjacently throughout the foil zone.

By using special applicators consisting of two or more chambers, it is possible to apply various solutions or suspensions in an integrated manner without mixing them with each other.

The size and thickness of the coating can be adjusted separately for each chamber. If desired, zones of different active substances or different concentrations can be made distinguishable by the use of different colorants. By drying the wet application, a film is obtained which can be suitably divided, for example by die-cutting, to obtain units with different active substances and/or active substance concentrations or active substance-free units. Films with different active substances and/or different active substance concentrations are required for the production of multiphasic preparations, for example for the production of contraceptives. The stability of the individual active substances is improved because active substances that are incompatible with each other can be spatially separated in the unit film. Foils for internal application can also be wrapped around commercially available tampons, for example. In the present invention, for the production of drug-containing drugs, a film-forming agent soluble in water and/or an organic solvent,
In particular, nonionic, water-soluble hydroxyalkyl ethers of cellulose are used, such as hydroxypropylcellulose, hydroxyethylcellulose and/or methylhydroxypropylcellulose.

Next, the present invention will be explained with reference to examples.

Cremopho used in the examples
11) EL® is a polycondensation product from ethylene oxide and castor oil. Furthermore, the cellulose used in the examples has a particle size of 1 to 150 A and a high weight of 150 to 25 A.
Powdered cellulose with 0/Z and particle size 300-50
It is made of fibrous cellulose having a high weight of 80 to 120 mm/kg. The formulations described in the Value Examples, with the exception of Examples 5 and 16, are primarily suitable for oral administration. Example 1 Preparation for 100 units: D-norgestrel 0.25 mm, ethynylestradiol 0.05 mm and polyoxyethylene polyoxypropylene polymer
0.84 ethyl alcohol
At 95.00 pm, the mixture was dissolved under the foot of Azusa, and a powder mixture consisting of hydroxypropylcellulose 16.93 pm and cellulose 16.93 pm was mixed into the same solution.

The suspension obtained is applied to a layer thickness of 500 mm on a suitable film former and then dried. The composition per unit is as follows: D-norgestrel 0.25 of 9
Ethinyl estradiol 0.05 9 polyoxyethylene polyoxypropylene polymer
0.84 3-hydroxypropylcellulose 16.93-9 cellulose 16.93-9
91 units of 35.00 is equivalent to an area of approximately 3 acre.

The appearance of the film is white and paper-like. The dry film has a thickness of about 170 mm. Example 2 Manufacture for 1000 units: Cremophor EL® 1.10 min.
152.00 Dissolve in the evening.

Micronized D-norgestrel 0.
25 evening powder and micronized ethinylestradiol 0.0
5. Suspend and optionally homogenize.

Hydroxypropyl cellulose in suspension. Mix 10 minutes of cellulose and 16.50 hours of cellulose.

The suspension obtained is applied to a layer thickness of 500 mounds on a suitable film former and then dried.

The composition per unit is as follows: D-/Lugestrel 0.25 Taethinylestradiol 0.05 Cremophor EL®
1.10 female hydroxypropylcellulose 22.10 female cellulose
16.50 pieces 940.
One unit of 00 female corresponds to an area of about 3 squares.

The appearance of the film is white and paper-like. The dry film has a thickness of about 170 mm. Example 3 Preparation for 100 units: 0.03 ml of D-norgestrel and 0.84 ml of polyoxyl-40-stearate are dissolved in 95.0 ml of ethyl alcohol with stirring.

Hydroxypropylcellulose 16 in the same solution
．． 93 Yu and cellulose 17.
Mix in a powder mixture consisting of 20 centimeters.

The resulting suspension is applied to a layer thickness of 500 mm on a suitable film former and then dried.

The composition per unit is as follows: D-norgestrel 0.03
o Polyoxyl-40-stearate 0.
84-9 hydroxypropyl cellulose 16
．． 939 cellulose
A C1 unit of 935.00 of 17.20 corresponds to an area of about 30.

The appearance of the foil is white and paper-like. The dry film has a thickness of approximately 170 mounds. Example 4 Preparation for a unit of 100: Dissolve 1.10 g of polyoxyethylene polyoxypropylene polymer in 152.0 g of demineralized water.

Micronized D norgestrel in the same solution 0
．． 03 suspension and optionally homogenized.

in the same suspension Hydroxyf.

Lopylcellulose 22.9 of 10 and cellulose
Mix with 16.77 pm. The resulting suspension was placed on a suitable film former for 50 minutes.
It is applied to a layer thickness of 0 mounds and then dried.

The composition per unit is as follows: D-norgestrel 0.03 imitation polyoxyethylene polyoxypropylene polymer
1.10 female hydroxypropylcellulose 22.10 female cellulose
16.77 evening 40.
One unit of 00 secrets corresponds to the area of about 3 carp.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 1701 m. Example 5 Production for 100 units: Fluocortolon methyl acetate 0.025 mm, glycerin 0.183 mm, and ethyl alcohol 30.00 mm
Dissolve in 0 ta.

Hydroxypropyl cellulose in the same solution 7.2
Mix in 92 evenings.

The solution obtained is applied to a layer thickness of 500 mm on a suitable film former and then dried.

The composition per unit is as follows: Fluocortolon methyl acetate 0.025 of 9 glycerin 0.183 female hydroxypropylcellulose 7.292 of 97
．． 91 units of 500 corresponds to an area of about 1 enemy.

The appearance of the foil is transparent. The dry film has a thickness of about 70 mm. This film is suitable for topical application. Example 6 Production for 100 units: 7-chloro-2-methylamino-5-phenylene-1,4-benzodiazepine-4-oxide 1000 units and polyoxyethylene polyoxypropylene sopolymer
0. Me and the ethyl alcohol
95.00 Dissolve in a lot of water.

Hydroxypropyl cellulose in the same solution 16.
93 evening and cellulose 7.
2. Mix in a powder mixture consisting of 23 ml.

The resulting suspension is applied to a layer thickness of 500 mm on a suitable film former and then dried.

The composition per unit is as follows: 7-chloro-2-methylamine/15-phenyl-9H-1,4-penzodiazepine-4-oxide 10.00
Polyoxyethylene polyoxypropylene polymer
0.84 9-hydroxypropyl cellulose 16.93 9-cellulose
One unit of 7.23M35.00 female corresponds to an area of about 3.

The appearance of the film is yellow and paper-like. The dry film has a thickness of approximately 170 mounds. Example 7 Preparation for 100 units: norethisterone acetate 1.00 mm, ethynylestradiol 0.03 mm and polyoxyethylene polyoxypropylene polymer
0.84 ethyl alcohol
Dissolve in 95.00 ta.

Hydroxypropyl cellulose in the same solution 16.
93 Yu and Cellulose 16.
Mix in a powder mixture consisting of 209.

The suspension obtained is applied to a layer thickness of 500 coats on a suitable film former and then dried.

The composition per unit is as follows: norethisterone acetate 1.00 9-ethinyl estradiol 0.03 female polyoxyethylene polyoxypropylene polymer
0.84 9-hydroxypropyl cellulose 16.93 cellulose
91 units of 935.00 in 16.20 corresponds to an area of approximately 3 acre.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 170 mm. Example 8 Preparation for 100 units: Norethisterone acetate 1.00 units, ethynylestradiol 0.03 units and propylene glycol 0.84 units in a mixture of methylene chloride 101,60 units and ethyl alcohol 26,40 units. dissolve in

A powder mixture consisting of hydroxypropyl cellulose 8.47 mm, hydroxyethyl cellulose 8.47 mm, and cellulose 16.19 mm was mixed into the same solution.

The suspension obtained is applied to a layer thickness of 500 mounds on a suitable film former and then dried.

The composition per unit is as follows: norethisterone acetate 1.00 9-ethinylestradiol 0.03 m0 propylene glycol 0.84 9-hydroxypropylcellulose 8.47 9-hydroxyethylcellulose 8.47 tacellulose
935 on 16.19
．． One unit of 00 copies corresponds to an area of approximately 3 lands.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 170 mounds. Example 9 Preparation for 1000 units: norethisterone acetate 1.00 units, ethynylestradiol 0.03 units and polyoxyethylene polyoxypropylene polymer
0. Hinayu and methylene chloride
101.60 evening and ethyl alcohol
25. Dissolve in the mixture with 40 minutes.

Hydroxyethyl cellulose in the same solution 16.
93 evening and starch 16.20
Mix in a powder mixture consisting of

The suspension obtained is applied to a layer thickness of 500 mounds on a suitable film former and then dried.

The composition per unit is as follows: /luethisterone acetate 1.009
Ethinyl estradiol 0.03 female polyoxyethylene polyoxypropylene polymer
0.84 9 hydroxyethylcellulose 16.93 9 starch
One 935.00 female unit of 16.20 is equivalent to an area of about 3 lands.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 170 mm. Example 10 Preparation for a unit of 100: 1.00 g of norethisterone acetate, 0.03 g of ethynylestradiol and 0.84 g of polyoxyl-40-stearate are dissolved in 95.0 g of ethyl alcohol.

Hydroxif in the same solution.

Lopyl cellulose 16.93 yen, lactose
Mix in a powder mixture consisting of 8.10 and corn starch. The resulting suspension is applied to a layer thickness of 500 mm on a suitable film former and then dried.

The composition per unit is as follows: norethisterone acetate 1.00 9-ethinylestradiol 0.03 9-polyoxy-40-stearate 0.84 9-hydroxypropyl cellulose 16.9 3-legged lactose
8.10 9 Corn Starch 8.10 91 units of 935.00 is equivalent to an area of about 3 acre.

The appearance of the foil is white and paper-like. The dry film has a thickness of approximately 170 mm. Example 11 Preparation for 100 scales: norethisterone (17Q-ethynyl-19-nor-testosterone) 1.00 ml, ethynylestradiol 0.03 ml and polyoxyethylene polyoxypropylene sopolymer
0.229 and ethyl alcohol
84.75 Evening and Wednesday
Dissolve in the mixture with 4.00 ml.

Hydroxypropyl cellulose in the same solution 16.
00 Yu and Cellulose 16.
A powder mixture of 0.00 and 0.00% is mixed in and optionally homogenized.

The suspension obtained is applied to a layer thickness of 600 mounds on a suitable film former and dried.

The composition per unit is as follows: norethisterone (17Q-ethynyl-19-nor-testosterone) 1.00 m9 ethinyl estradiol 0.03 female polyoxyethylene polyoxypropylene polymer
0.22 9-hydroxypropyl cellulose 16.00 cellulose
The area per unit of 16.00 females and 33.25 females is approximately 3.

The appearance of the film is white and paper-like. The dry foil has a thickness of about 230 mm. Example 12 Production for 100 mountain units: Finely powdered grease oxepide (4- Methylene-semicarbazide) 4.0 Wed.
Polyoxyl-40-stearate dissolved in 152.0 ta
0.9 ml and optionally homogenized.

15.0 ml of hydroxyethyl cellulose and 15.19 ml of calcium carbonate were mixed into the same suspension.

The suspension obtained is applied to a layer thickness of 500 mm on a suitable film former and dried.

The composition per unit is as follows: Glysoxepide (4-{4-[8-(5-methyl-isoxazole-3-carboxyamido)-ethyl]-benzenesulfonyl}-1,1- (hexamethylene-semicarbazide) 4.00m9 Polyoxy-40-stearate 0.90 9-hydroxyethyl cellulose 15.00 double 9 calcium carbonate 15.10 secret 35.0
0 female 1 unit corresponds to an area of about 3.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 170 rms. Example 13 Production for 100G unit: Dissolve 0.030 g of norgestrel in 40.000 g of methylene chloride and 55.0 g of ethanol.

Silicone oil in the same solution 0.84
0 evening, methyl cellulose 6.93
0 evening, poly-N-vinylpyrrolidone 10.000
Starch and Starch 17. Mix in 200 g of starch and homogenize if necessary.

The suspension obtained is applied to a layer thickness of 500 mm on a suitable film former and dried.

The composition per unit is as follows: D-norgestrel 0.0309
silicone oil 0.840 female methyl cellulose 6.930 9 poly-N-vinylpyrrolidone 10.000 9 lees
Powder 17200 935.
91 units of 00 corresponds to an area of about 3.

The appearance of the film is white and paper-like. The dry film has a thickness of about 170 mm. Example 14 Manufacture for 100 piles: Polyoxyethylene polyoxypropylene polymer 0.84 ml of ethyl alcohol 95.00 ml of ethyl alcohol while stirring, dissolve hydroxypropylcellulose 17.08 ml of cellulose in the same solution.
17. Mix in a powder mixture consisting of 0.8 oz.

The suspension obtained is applied to a layer thickness of 500 mounds on a suitable film former and then dried.

The composition per unit is as follows: Polyoxyethylene polyoxypropylene polymer 0.84 mg Hydroxypropylcellulose 17.08 of 9 Cellulose 17.08 of 935
．． 9 examples of 00 15 Manufacture for 100 units: Saccharin 0.04 hours, Creamessence 0.04 hours, Polyoxyethylene polyoxypropylene polymer 0.40 hours, Ethyl alcohol 79.00 hours and Water 4.00 hours. Dissolve in a mixture with.

Iron fumarate (D) 30.0 in the same solution
0 evening, hydroxypropyl cellulose 15.00
Yu, cacao 5.52 Yu and cellulose 4.00
Mix the water and homogenize if necessary.

The suspension so obtained is placed on a suitable film former.
．． 5 side layer thickness and then drying.

The composition per unit is as follows: Iron fumarate (b) 30.00 9-hydroxypropylcellulose 15.00 9-cellulose 4.00 9-polyoxyethylene polyoxypropylene polymer
0.40 Leg Strength Khao
5.52 9 saccharin
0.04 female cream essence
Weight per 91 unit of 0.04
91 units of 55.00 corresponds to an area of approximately 3.

The appearance of the foil is pale reddish brown. Example 16 Foil for intra-abdominal use: The production of the film is carried out analogously to Example 11.

The composition per unit is as follows: 5-morpholinomethyl-3-(5-nitro-1-methyl-2-imidazolyl)-methyleneamino-2-oxazolidinone HC1 1 100
．． 0 of 9 Ctemophor EL® 8.4 of 9 Methyl Hydroxypropyl Cellulose
169.29 cellulose
Weight of 91 units of 72.4
91 units of 35.00 corresponds to an area of about 8 x 4.

The appearance of the foil is pale yellow. Same foil (1 unit)
Wrap around a commercially available tampon or wrap the foil itself into a thin tube.

Example 17 Two-phase preparation 1 part: 21 units containing active substance 2 parts: 7 units without active substance 1 part Preparation for 300 units: o norgestrel 0.75 pm, ethinylestradiol 0.15 pm and polyoxyethylene polyoxypropylene polymer
0.54 ml of ethyl alcohol
237.00 Evening and Wednesday
Dissolve in the mixture with 12.00 pm.

Hydroxypropyl cellulose in the same solution 44.
28 Yu and cellulose 44.
28 minutes and homogenize if necessary.

Preparation for 2 parts and 100 units: 0.18 parts of polyoxyethylene polyoxypropylene polymer are dissolved in a mixture of 79.0 parts of ethyl alcohol and 4.0 parts of water.

Hydroxypropyl cellulose in the same solution 14.
91 Yu and cellulose 14.
91 days and optionally homogenized.

The suspension thus obtained is applied to a two-chamber special applicator (inside the chamber: one
= rat fence; 2 = 18 side) on a suitable film former to a layer thickness of 0.5 side and then dried.

Suitable division into 18 x 18 units, for example by punching, will result in 3 parts containing the active substance throughout the foil.
The unit is divided into one unit containing no active substance. Any number of pieces can be obtained from the film strip, with three units containing the active substance and one unit not containing the active substance. The composition of each unit is as follows: Area per unit: approx. 3 pieces 2 Appearance: white Example 18 Three-phase preparation (preparation of two-step active substance) 1 part: 0.05 of Norgestrel 2 parts of 11 units containing ester and ethinylestradiol 0.05 double 9:
Preparation for 1100 units: 3 parts of 10 units containing D-norgestrel 0.125 and 9-ethinylestradiol 0.050 parts: 1 part of 7 units containing no active substance: D-norgestrel 0.055 parts;
Cetinylestradiol 0.055 and polyoxyethylene polyoxypropylene polymer
0.198 ml of ethyl alcohol
86.900 Evening and Wednesday
4. Dissolve in the mixture with 400 ml.

Hydroxypropyl cellulose in the same solution 16.3
46 Yu and cellulose 16.3
46 and homogenized if necessary.

Preparation for 2 parts 100 units: 0.125 units of norgestrel, 0.050 units of ethinylestradiol and polyoxyethylene polyoxypropylene polymer
0.180 ml of ethyl alcohol
79.000 Evening and Wednesday
Dissolve in the mixture with 4,000 ml.

Hydroxypropyl cellulose in the same solution 14.8
23 Yu and cellulose 14.
822 and homogenized if necessary.

Preparation for 3 parts 70 units: Polyoxyethylene polyoxypropylene polymer 0.189 ethyl alcohol 82.950 Yuto Mizu
4. Dissolve in the mixture with 200 g.

Hydroxif in the same solution.

Lopyl cellulose 15.656 cellulose
15.655 ml and homogenized if necessary. The suspension thus obtained is applied onto a suitable film forming machine using a 3-chamber special applicator (inside: 18 sides per chamber) and dried.

For example, by punching out appropriate divisions into units of 18 x 18 skin for 1 part, 18 x 19.8 sail for 2 parts, and 18 x 28 ribs for 3 parts, the active ingredient content can be reduced throughout the foil. Three different units are divided. A formulation having 1 part of 11 units, 2 parts of 1 mountain unit, and 3 parts of 7 units can be divided from the foil band. The composition per unit is as follows: Example 19 Three-phase formulation: 11 units containing 1 part: 0.05 parts of D-norgestrel and 0.05 parts of ethinyl estradiol 2 parts: 0.05 parts of D-norgestrel. 1
25 Cape and Ethinylestradiol 0.
050-9 Containing 1 ■ Unit 3 parts: iron fumarate (b)
Manufacture for 7 units 1 part 110 mountain units with a value of 50.00: Edible yellow Qin snake. 2 (Tartrazine; EI02) Dissolve 0.066 ml in water 4.400 ml, then ethyl alcohol 8
6. Mixed into 900 ta.

Add 0.0% D-norgestrel to the same solution.
055 evening, ethinyl estradiol 0.0
Dissolve 0.1% of polyoxyethylene polyoxypropylene polymer and 0.1% of polyoxyethylene polyoxypropylene polymer.

Hydroxypropyl cellulose in the same solution 16.3
13 Yu and cellulose 16.
313 and homogenized if necessary.

Manufacture of 2 copies for 1000 units: Edible orange dye shame. 2 (Sunset Yellow: EII
O) 0.065 evening on Wednesday
4.000 melted in the evening,
Followed by ethyl alcohol 79.0
Mixed into 00ta.

D-norgestrel 0.1 in the same solution
25 evening, ethinylestradiol 0.05
Dissolve 0.0 and polyoxyethylene polyoxypropylene polymer 0.180.

Hydroxypropyl cellulose in the same solution 14.7
90 evenings and cellulose 14.
790 ml and homogenized if necessary.

Manufacture for 3 parts and 70 units: Saccharin 0.042 m,
Cream essence 0.042 and polyoxyethylene polyoxypropylene polymer
0.4069 and ethyl alcohol
55.300 Evening and Wednesday
2. Dissolve in the mixture with 800 g.

Iron fumarate (0) in the same solution 35.0
00 evening, hydroxypropylcellulose 17.50
0 evening, cacao 5.950
Evening and cellulose 4.06
0.0 and homogenized if necessary.

The suspension so obtained is applied using a three-chamber special applicator (inside: 18 ribs per chamber) onto a suitable film-forming machine and then dried.

For example, by punching out appropriate divisions into units of 18 x 18 ribs for 1 part, 18 x 19.8 legs for 2 parts and 18 x 28 skin for 3 parts, the active substance content will be reduced throughout the foil. It is possible to separate three units with different values.
It is possible to divide the formulation from the foil band into one part with 11 units, with two parts with 1.5 units, and with three parts with 7 units. The composition per unit is as follows: Example 20 Preparation for 100 units: ○-norgestrel 0.15 units, ethinylestradiol 0.03 units and polyoxyethylene polyoxypropylene polymer
0.84 ethyl alcohol
It melted with some damage during the 95.00 ta.

Hydroxypropyl cellulose in the same solution 16.
99 evening and cellulose 16
．． Mix in a powder mixture consisting of 99 g.

The suspension obtained is applied to a layer thickness of 500 mounds on a suitable film former and then dried.

The composition per unit is as follows: D-/Lugestrel 0.15 9-ethinyl estradiol 0.03 polyoxyethylene polyoxypropylene polymer
0. Matsume Hydroxypropyl Cellulose 16.999 Cellulose
91 units of 16.99m935.00 is approximately 3
It corresponds to the area of the earth.

The appearance of the film is white and paper-like. The dry film has a thickness of approximately 170 French skins. Example 21 Preparation for 100 units: Dissolve 1.5 units of D-norgestrel and 0.3 units of ethinyl estradiol in 477.7 units of alcohol.

(Solution A) Polyoxyethylene polyoxypropylene polymer 1.5 ml of water
23.0 Melt in the evening.

(Solution B) Combine Solution A and Solution B together (Solution C) Hydroxypropylcellulose 88.1 and Cellulose Spots. 6. Mix carefully and pass through 1.2 skin sieve and pour into solution C (Suspension D). A layer thickness of 600 mounds is applied on top and then dried.

The composition per unit is as follows: D-norgestrel 0.15 9 ethinyl estradiol 0.03 mg hydroxypropyl cellulose 8.81 9 cellulose 8.86 9 polyoxyethylene polyoxypropylene polymer
The area per unit of 918.00 females of 0.15 is 144th.

Claims (1)

[Claims] 1 Containing active ingredients up to 60% by weight of the oil,
In preparing pharmaceutical foils for oral administration or external application, the active ingredient and exfoliating agent are dissolved in a solvent consisting of water or one or more physiologically harmless organic solvents or mixtures thereof, and then the foil is prepared. Non-ionic, water-soluble hydroxyalkyl ethers or methyl hydroxyalkyl ethers of cellulose, methylcellulose, ethylcellulose or mixtures of the two therein as forming agents, and fillers are added, homogenized and subsequently the same solution is added. or the suspension is applied on a film forming machine to a layer thickness of 0.1 to 2 mm, and the wet material is dried to form a uniform dry film with a thickness of 0.05 to 1 mm, Manufacturing method for pharmaceutical oil.