JPS6263513A - Film preparation - Google Patents

Abstract

PURPOSE:A external film preparation having improved adhesivity to the skin, mucosa in the oral cavity, etc., being brought into contact with the affected part to cover it in use, containing a drug in a film comprising hydroxypropyl cellulose as a main component. CONSTITUTION:An external film preparation containing a drug such as local narcotic, an antibacterial agent containing antibiotic, etc., chemotherapeutics containing antifungal agent, anti-inflammatory agent containing steroid drug, etc., in a film which comprising hydroxypropylcellulose (HPC) having preferably about 150-400 viscosity (cps) as a main component and about 0.05-0.1mm, especially about 0.07-5mm thickness. The preparation not only has the above- mentioned effect but also can administer a drug to a patient smoothly because of a thin dosage form. Further since a film is dissolved in a period convenient for remedy, it has improved adhesivity to the affected part and after treatment is carried out extremely well.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a pharmaceutical film formulation, and more specifically, it contains an active ingredient that is intended to be brought into direct contact with the oral cavity, ear-nose mucous membrane, skin, etc. The present invention relates to a film preparation made of RPC (hydroxypropylcellulose).

(Prior Art) In order to apply a topical drug to an affected area, it is necessary to bring the affected area into contact with the drug for a certain period of time, and various efforts have been made to create dosage forms for this purpose. For example, the active ingredient is mixed with a viscous ointment base, etc., and applied to the affected area, and the liquid is sprayed with a device to treat the affected area.
Techniques have been applied, such as applying the active ingredient to the affected area using physical means such as a bandage, or applying the active ingredient soaked in gauze or the like to the affected area using physical means such as a bandage.

(Problems to be Solved by the Invention) However, depending on the above-mentioned means, there are cases in which external medicines do not necessarily come into contact with the affected area effectively and the expected medicinal effect cannot be found. For example, in the oral cavity, the best way to apply ointment is to wash it out from the affected area with mucus such as saliva and cut off contact with the affected area after a certain period of time, and in the nasal cavity or ear cavity, it is difficult to physically apply ointment etc. directly. There was a level of difficulty.

The present invention attempts to overcome the above-mentioned physical difficulties by devising the dosage form of the drug.

(Means for solving problems) The gist of the present invention is as follows.

■It is a film whose main component is IIPC (hydroxypropyl cellulose).

■It contains effective pharmaceuticals in the film.

Moreover, the gist of the method for producing a pharmaceutical preparation according to the present invention is as follows.

0 Dissolve commonly used active pharmaceuticals in a solvent.

■Dissolve HPC in the above solution.

(2) The above solution is poured into a certain casting mold, and then the solvent is distilled off to form a film.

The present invention will be explained in more detail below along with the manufacturing method.

Conventional methods can be used to dissolve over-the-counter medicines in solvents. Since the solvent will be distilled off later, any solvent may be used, but it is desirable to use a solvent that has little effect on the human body. Examples of the organic solvent include alcohols such as ethanol and methanol, but ethanol is preferable.

Although water can also be used, it is more desirable to use water that can be easily distilled off for later steps.

If a commonly used drug is soluble only in an organic solvent, it is better to use an organic solvent, and if it is soluble only in water, it is better to use water.

The amount of the solvent used in the present invention can be appropriately increased or decreased depending on the amount of HPC, which will be described later.

The amount of the solvent in the present invention can be determined, for example, so that the concentration of It l)C is about 1-10%, but more preferably about 4% is sufficient.

The amount of the pharmaceutical agent applied to the present invention can be appropriately increased or decreased depending on the needs of the affected area to be used.

Next, 11)) C is dissolved in the above solvent. Although it is conceivable to melt IIPC before melting the over-the-counter medicine, it is preferable to melt the applicable medicine first in order to form a uniform film.

IIPC is a nonionic cellulose derivative produced by reacting cellulose with propylene oxide, and has the following structure.

[Wherein, R is hydrogen or (-C112CIl (CIl3
)-0) Il+-11 group, m represents an integer of 1 or more. ]If P C ■? Its properties and physical and chemical properties vary depending on the degree of bonding. In carrying out the present invention, the viscosity (C
r'S) of about 150 to 400 has been found to be desirable.

If the amount of IPC (dissolved) is small, the resulting film will be thin; if the amount is large, the film will be thick. Although thin films have excellent flexibility, they tend to melt when applied to the affected area and become difficult to handle with tweezers. Films are not preferred for purposes of this invention. Although a thick film has an increased function as a support when applied to an affected area, it is inferior in terms of flexibility and also in terms of usability such as a feeling of something strange felt by the patient.

As shown in Test Example 3 below, in carrying out the present invention, it is necessary to devise the thickness of the film. The thickness of the film is preferably about 0.05 to 0.1 m+n, preferably about 0.075 mm. At this level, a sufficient effect can be obtained from the release effect of the applied drug.

In carrying out the present invention, plasticizers can also be added. The plasticity of the film 2 according to the invention can be increased by adding plasticizers. As the plasticizer, for example, triacetin (glycerol triacetate) or the like can be used. The addition of plasticizer is 1 to the solution.
0% or less is desirable. It has been found that if more than this is added, the plasticizer will be exposed on the surface of the resulting film.

The solution in which the applicable drug and HPC are dissolved is poured onto a cast of an appropriate size. The size of the cast can be appropriately determined depending on the size of the film to be produced. Various cast shapes such as square, rectangle, circle, and oval can also be used. The cast is preferably made of synthetic resin such as Teflon.

With materials such as glass history, the produced film adheres to the cast and cannot be easily peeled off, which is inconvenient.

Depending on the size of the cast and the amount of solution poured, the thickness of the produced film can be 81M. For example, in the example of a 5 cm x 10 (m) rectangular Kiosu production, 600 mg of HP C produces 0.075
It has been found that films of mm can be produced.

The solvent of the solution poured onto the cast can be distilled off by leaving it to stand.

Further, if the solvent does not evaporate to a ratio of 3:1, it can be distilled off by a method such as reduced pressure.

After distilling off the solvent, a film-like formulation according to the present invention can be obtained from the cast.

Pharmaceuticals applicable to the present invention include all pharmaceuticals that have uses as external preparations.

In this specification, external preparations include all dosage forms except oral preparations and injection preparations, and "external use" shall mean this concept.

The preparation according to the present invention can be applied by applying it directly to the affected area.
J: Can be used by letting.

The preparation according to the present invention can be applied to all affected areas including (in addition to the oral cavity, the nasal cavity, the ear cavity, the skin, the anus, the vagina, the genitals, etc.).

The present invention can be extremely widely applied in all fields such as dermatology, oral surgery, otolaryngology, venereal disease, and urology. Furthermore, since it has been found that 1(r'C) has no effect on the human body, the film according to the present invention can be extremely well applied to affected areas during surgical operations.

Examples of pharmaceuticals applicable to the present invention include local anesthetics, antibacterial agents including antibiotics, chemotherapeutic agents including anticancer agents and antifungal agents, anti-inflammatory agents including steroid drugs, etc.
Examples include, but are not limited to.

Specific examples of pharmaceuticals that can be used in the present invention include, for example, local anesthetics such as ethyl aminobenzoate, propylene, chloropropylene, tetracaine, lidocaine, and dibucaine. Examples of antibiotics include chloramphenicol, chloramphenicol palmitate, thiamphenicol, and tetrazycline. Examples of anti-inflammatory agents include anti-inflammatory agents such as guaiazulene, anti-inflammatory enzyme agents such as lysozyme chloride, and steroid agents such as cortisone, paramethacin, dexamethasone, and prednisolone. Also,
Examples of antifungal agents include miconazole nitrate, isoconazole I'rrjate, and ethicotpool. It is clear that the above-mentioned drugs are only examples of the present invention and the present invention is not limited thereto.

(Effects of the Invention) The present invention has achieved the following technical effects.

■It has become possible to create a dosage form that has excellent adhesion to skin and mucous membranes such as the oral cavity, which was previously considered difficult to do using methods such as soft gelatin and bandages.

■Since it has become possible to use physically thin dosage forms, it has become possible to administer pharmaceuticals without interfering with the patient's daily life.

■The film that serves as the base dissolves at a convenient time for treatment, resulting in excellent adhesion to the affected area, and the base itself dissolves after the medicinal effect of the administered drug has finished, making post-treatment extremely easy. Ta.

(Next page below) (Example) The present invention will be further explained below by presenting Examples and Test Examples according to the present invention.

Example 1 Approximately ioml of ethanol was placed in a flask, 20 mB of chloramphenicol, and 20 mg of tetracaine.

2.4 mg of guaiazulene and 2.4 mg of triacetin
NgP so that 1 degree is 4%! Gradually add and dissolve 2.4 g of IIPC (Nippon Soda (41) IPC-M). Then add ethanol to bring the total volume to 80ml.
shall be.

116 C1l+, width 10 Cff1, height Q, 5
Pour 1 liter of ethanol and 20 ml of peel into a Teflon cast with a diameter of 2 cm, and open at about 40:6.
do. After confirming that the entire amount of ethanol has been distilled off,
Obtain a film-like formulation.

When the above-mentioned film preparation was cut into pieces of a size according to the location and area of the affected area and applied to the ulcerated area of a patient with sublingual membrane ulcer, the anesthetic effect was felt after about 15 minutes, and about 3 to 30 minutes. Lasted for 4 hours.

2 Pour approximately 60ml of ethanol into a Fuyosco, dissolve 20mg of ethyl p-aminobenzoate and triacetin to a final concentration of 4%, and dissolve I-IPC (Nippon Soda (HP CM made by 11J) Gradually add 2.4 g. Then add ethanol to bring the total volume to 80 ml.

20 ml of the above ethanol solution was placed on a Teflon cast measuring 6 cm long, 10 cm wide, and 0.5 cm high.
Pour in and leave for about 40 hours. After confirming that the entire amount of ethanol has been distilled off, a film-like preparation is obtained.

When the above film preparation was cut into pieces of a size according to the location and area of the affected area and applied to the ulcerated area of a patient with sublingual membrane ulcer, the anesthetic effect was felt after about 15 minutes, and it took about 2 hours. It lasted.

Test Example 1 Approximately 60 ml of ethanol was placed in a flask, and four types of HPC (Nippon Soda (111! JHPC-3) with different properties were placed in a flask.
L, L, M, and H) 2.4g were gradually added and melted. Then add ethanol to bring the total volume to 80 ml.

Pour 20 ml of the above ethanol solution into a Teflon cast measuring 5 cm in length, 10 marks in width, and 0.5 cm in height, and leave to stand. After confirming that the entire amount of ethanol has been distilled off, a film-like preparation is obtained.

The above film preparation is cut into a circular shape with a diameter of about 28 mm.

Drug release device 4 (approximately 45mm in diameter) as shown in Figure 1.
1. It has a cylindrical shape with a height of about 45 mm, and 36°C water is circulated around it. The inner cylinder is filled with distilled water and constantly stirred with a magnetic stirrer. A collagen membrane (Maypunk (Meiji Seika Co., Ltd., registered trademark)) is placed on the top of the inner cylinder. ) The above film preparation is placed on top of the collagen membrane.

After a certain period of time, a certain amount of the solution in the inner cylinder was collected from the vial camp using a microsyringe, and the amount of eluted HPC was measured using a differential refractometer. The relationship between the elution amount and time when the maximum elution amount is 100% is the second
As shown in the figure.

It is preferable that HPC as a base does not dissolve for 2 to 3 hours when the drug exerts its effects on the affected area.HPC-M (viscosity (
CPS) 15'C to 400) was found to be the most desirable.

Test Example 2 Put about 60 ml of ethanol in a flask, dissolve 20 mg of chloramphenicol and triacetin to a final concentration of 4%, and add four types of RPC with different properties (Nippon Soda (11)). Manufactured by HP C-3L.

Gradually add and dissolve 2.4 g of L, M, and [I]. Then add ethanol to bring the total volume to 80ml.

Thereafter, a film-like preparation was obtained in the same manner as in Test Example 1,
It was placed on the same drug release measuring device as in Test Example 1. After a certain period of time, a certain amount of the internal solution was collected in the same manner as in Test Example 1, and the amount of chloramphenicol was measured by high performance liquid chromatography. FIG. 3 shows the relationship between the elution level and 1lli when the maximum elution amount is 100%. It is desirable for the entire amount of chloramphenicol as an antibacterial agent to be eluted within about 45 minutes after the injection, and it was found that RPC-H was insufficient and HPCM was sufficient. .

Test Example 3 Put about 60 ml of ethanol in a flask, add 20 mg of chloramphenicol, and triacetin four times before and after each hour to give a concentration of 4%. Add a little more than 1 volume of HPC-M) and dissolve. After that, add ethanol to make the total volume 80ml.

At this time, f (PC repellency is 2.40g, 3.60g, 4
．． 80g.

and 6. Four types of solutions of OOg were prepared.

Thereafter, a film-like preparation was obtained in the same manner as in Test Example 1. When the thickness of the film was determined to be 9 JtlJ, they were 0.075 mm, 0.10 mm, 0.15 mm, and 0.20 mm, respectively.

These four types of films were placed on the same drug release measuring device as in Test Example 1. After a certain period of time, a certain amount of the internal solution was collected in the same manner as in Test Example 1, and the concentration of musoenicol was measured using a high-speed liquid analyzer. FIG. 4 shows the relationship between elution amount and time when the maximum elution amount is 100%. It is desirable that the entire amount of chloramphenicol as an antibacterial agent be eluted within about 45 minutes after administration, and 2.40 g is sufficient, but if the amount of HPC is more than that, chloramphenicol will elute. It was found that the quantity was insufficient.

In addition, when a film preparation was prepared using a similar method with an amount of HPC of 1.60 g, an extremely thin film was formed, which was found to be unfavorable in terms of handling as it may cause rupture during the bottle setting process. Ta.

Test Example 4 Put about 6 On+ 1 ethanol in a flask, and put p-
20mg of ethyl aminobenzoate and triacetin were dissolved to a final concentration of 4%, and four types of RPC with different properties (Nippon Soda (barrel! Il!! HPC-SL, LS) were dissolved.
Gradually add 2.4 g of the four types (M and H) and dissolve. Then add ethanol to bring the total volume to 80 ml.

Thereafter, a film-like preparation was obtained in the same manner as in Test Example 1, and placed on the same drug release measuring device as in Test Example 1. After a certain period of time, collect a certain amount of internal solution in the same manner as in Test Example 1,
The amount of ethyl p-aminobenzoate was determined by high performance liquid chromatography. FIG. 5 shows the relationship between elution amount and time when maximum elution (2) is taken as 100%. It is desirable that the entire amount of ethyl p-aminobenzoate as a local anesthetic be eluted approximately 30 minutes after administration;
It was found that +1 was insufficient and lI P CM was sufficient.

[Brief explanation of the drawing]

FIG. 1 is a diagram showing a drug release measuring device for measuring the amounts of RPC and pharmaceuticals eluted from a film according to the present invention in a test example. (2) is a vial cap, which is used to inject a microsyringe and turn the internal solution. (2) is a perfusion system that circulates water at 36°C to maintain a constant temperature. ■ is a magnetic stirrer. (2) is a collagen membrane on which the film preparation of the present invention is placed. FIG. 2 is a diagram showing the relationship between the elution amount of l P C and time in Test Example 1.・ stands for HP C-H, O stands for HP CM, △ stands for I (P C-L, and mouth stands for RP.
C-SL respectively. The vertical axis shows the elution M (% when the large Q elution amount is 100) of RPC, and the horizontal axis shows time (hours). FIG. 3 is a diagram showing the relationship between the elution amount of chloramphenicol and time in Test Example 2.・ stands for HP C-H, O stands for 1 (PC-M, △ stands for HP
CL and mouth represent RP CS+, respectively. The vertical axis is the elution amount of chloramphenicol (the maximum elution amount is 1
00), and the horizontal axis shows time (minutes). FIG. 4 is a diagram showing the relationship between the elution amount of chloramphenicol and time IH1) in Test Example 3.・ indicates the case of 1500 mg per cast, O indicates the case of 1200 mg per cast, △ indicates the case of 900 mg per cast, and mouth indicates the case of 6 per cast.
00 mg. - The vertical axis shows the elution amount of chloramphenicol (% when the maximum elution amount is 100), and the horizontal axis shows time (minutes). FIG. 5 is a diagram showing the relationship between the elution amount of ethyl p-aminobenzoate and time in Test Example 4.・HPC-
H, O stands for HPC-M, △ stands for HPC-L, and mouth stands for H and PC-SL, respectively. The vertical axis shows the elution amount of ethyl aminobenzoate (% when the maximum elution amount is 100), and the horizontal axis shows time (minutes).

Claims (1)

[Claims] An external film preparation containing HPC as a main component and pharmaceuticals.