JP2011251954A - Oral film formulation having safety valve - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a film formulation having a safety valve, which can be easily stored without inducing deformation or degradation, maintains a drug amount and can be safely taken without water.SOLUTION: The film formulation with a safety valve has a minimum span length of 15 mm or more and an area of 175 mmor more, and is provided with a valve cut that does not reach the rim.

Description

  The present invention relates to an oral film preparation having a safety valve that can be safely taken without obstructing the airway.

In recent years, with the acceleration of aging, improvement of medication compliance has become a major theme.
One of the causes of reduced medication compliance is dysphagia. Depending on the disease, water intake may be restricted, and it may be difficult to take a medicine with water while bedridden. Many reports and proposals for solving the problems have been made regarding such problems of the actual situation (for example, see Non-Patent Documents 1, 2, and 3).
Wafers and jellies have been raised as dosage forms particularly suitable for improving the medication properties of elderly people (for example, see Non-Patent Document 4).

  On the other hand, solid preparations that disintegrate and dissolve rapidly in the oral cavity are drugs not only for elderly people but also for infants and children who are not good at swallowing tablets, migraine, angina, allergic asthma, etc. This dosage form is also suitable for drugs for lifestyle-related diseases such as oral medication, hypertension, diabetes, hypercholesterolemia, and hyperuricemia.

  In order to cope with these situations, in recent years, the development of orally disintegrating tablets that easily disintegrate in the oral cavity without water and orally disintegrating film preparations has become active. Among these, the orally disintegrating film preparation can be disintegrated with a smaller amount of saliva than the orally disintegrating tablet due to its thinness, and is expected to be widely used in various drugs from the viewpoint of safety and ease of taking medicine. ing.

  The orally disintegrating film preparation is a film preparation for oral administration that can completely mask the taste, smell, etc. of the drug contained in the drug-containing layer, and the drug is encapsulated inside the oral administration agent There has been proposed a film preparation that is adapted to the above (for example, see Patent Document 1).

  In addition, in order to form a stable film preparation under high and low humidity, a stable film preparation with high flexibility and low stickiness under high and low humidity while maintaining fast solubility has also been proposed. (For example, refer to Patent Document 2).

  Moreover, the manufacturing method of the film formulation which was excellent in a softness | flexibility and adhesiveness, and provided oral-mucosal-adhesive property and sustained release property is proposed (for example, refer patent document 3).

  Furthermore, it is a film-like troche for the purpose of sterilization and disinfection in the oral cavity, and it adheres to the mucous membrane in order to overcome the shortcomings of medicinal effects being lost immediately after being chewed or swallowed. A film-like troche that exhibits a medicinal effect by being gradually dissolved by the water and releasing the drug continuously has been proposed (for example, see Patent Document 4).

JP 2005-289868 A JP 2005-232072 A Japanese Patent Laid-Open No. 62-135417 JP 2001-288074 A

Report “Survey on the Actual Conditions of Elderly People and Their Consciousness about Dosage Forms” Magazine “Ther Res” 27 (6) June 20, 2006 Thesis "New formulation and packaging container optimal for administration to the elderly" magazine "Pharmacia" 30 (12) 2004 Published by Japan Pharmaceutical Association The paper "Development of new preparations for the elderly-Basic study on preparation of gelatin jelly containing indigestible dextrin"-Journal of Hospital Pharmacy 22 (5) 1996 Published by Japan Hospital Pharmacy Society The paper “Development of preparations for improving drug compliance and oral care for the elderly”, “Journal of the Japan Geriatrics Society” 45 (5) 2008 Published by Japan Geriatrics Society

Methods for taking oral film preparations are roughly divided into two.
When using it by adhering to the oral mucosa, such as a stomatitis drug or a lozenge, apply the preparation directly to the application site and apply it.
In the case of an orally disintegrating film preparation imparted with rapid disintegration, the preparation is usually placed on the tongue, sandwiched between upper jaws, disintegrated, and then swallowed with saliva. In this case, when the amount of saliva is extremely small such as xerostomia, or when the child has taken the wrong way, there is a risk of reaching the throat without fully disintegrating the film. There is a case. In the worst case, the airway can not be secured by covering the throat with a film, and it may be considered that the patient suffers from severe dyspnea. In the above-described prior art, no attempt has been made to pose a problem or to solve such a problem.

In the case of tablets, the General Rules for Formulation in the 15th revised Japanese Pharmacopoeia Manual (Yodogawa Shoten) 15. As described on the tablets, the size is circular and the maximum diameter is 1.5 cm. This is a measure for avoiding the above danger.
In the description of the dosage form of the pharmaceutical manufacturing guidelines separate volume Pharmaceutical Manufacturing [Import] Approval Standards 2000 Edition (Jiho), it is stated that “Chewable tablets with a diameter of more than 1.5 cm are not allowed except for donuts”. This is a measure for ensuring breathing through the hole in the center of the tablet when the tablet remains in the throat.

(Object of invention)
The present invention was made in view of the problems of the above-described prior art oral film preparations, and can be easily stored without being deformed or deteriorated, ensuring a drug amount, and safely without water. It aims at providing the film formulation which has a safety valve which can be taken.

The present invention
An oral film preparation having a safety valve characterized in that a film preparation having a minimum delivery length of 15 mm or more and an area of 175 mm ² or more and provided with a valve notch that does not extend to the periphery.

  ADVANTAGE OF THE INVENTION According to this invention, the film formulation which has the safety | security which can be taken safely with or without water without losing disintegration and flexibility which are the characteristics of a film formulation, and does not reduce a drug amount. can do. In particular, it is possible to provide a film preparation that secures the maximum amount of drug by effectively using the entire film preparation without any loss by making a valve-like cut instead of completely opening a hole. .

When the minimum delivery length is 15 mm or more and smaller than the oral film preparation having an area of 175 mm ² or more, the oral film preparation is less likely to block pores.

  Specific examples of drugs include hypnotic sedatives / anti-anxiety drugs, antiepileptic drugs, rhinitis drugs, antipyretic analgesic / anti-inflammatory drugs, anti-Parkinson drugs, neuropsychiatric drugs, local anesthetics, cerebral circulation metabolism improvers, antispasmodics , Antipruritic, cardiotonic, arrhythmic, diuretic, antihypertensive, vasoconstrictor, vasodilator, hyperlipidemic, respiratory stimulant, antitussive, expectorant, antitussive, a bronchial Dilators, mouthwashes, antidiarrheals / intestinals, anti-ulcers, digestive stomachs, antacids, constipation, antibacterials, nourishing tonics, gout, diabetes, antibiotics, antibacterials Drugs, osteoporosis drugs, skeletal muscle relaxants, antirheumatic drugs, hormone drugs, alkaloid narcotics, anticoagulants, antineoplastic drugs, antihistamines, erectile dysfunction drugs, allergy drugs, etc. .

More specifically, the following substances are listed.
Hypnotic sedatives / anti-anxiety drugs: Estazolam, nitrazepam, diazepam, phenobarbital, alprazolam, chlordiazepoxide

  Antiepileptic drugs: phenytoin, carbamazepine, sodium valproate

  Antipyretic analgesics: aspirin, acetaminophen, etenzamide, ibuprofen, lysozyme chloride, mefenamic acid, diclofenac sodium, ketoprofen, indomethacin, phenacetin, caffeine

  Antiparkinsonian drugs: amantadine hydrochloride, levodopa, trihexyphenidyl hydrochloride

  Psychiatry & Neurology: Sullipid, haloperidol, chlorpromazine, reserpine, risperidone, fluvoxamine maleate

  Local anesthetics: procaine, lidocaine

  Drugs that improve cerebral circulation metabolism: meclofenixate hydrochloride, nicergoline, tartilelin

  Antispasmodic: scopolamine hydrobromide, papaverine hydrochloride, atropine sulfate, propantheline bromide

  Antipruritics: diphenidol hydrochloride, dimenhydrinate, meclizine hydrochloride, chlorpheniramine d-maleate, scopolamine hydrobromide

  Cardiotonic drugs: digoxin, ubidecalenone, ethylephrine hydrochloride, dopamine hydrochloride

Arrhythmic drugs Mexiletine hydrochloride, propranolol hydrochloride, pindolol, atenolol

  Diuretics: isosorbide, furosemide, hydrochloride thiazide, spironolactone, triamterene, naphthopidyl

  Antihypertensive drugs: delapril hydrochloride, captopril, perindbryl erbumine, hydralazine hydrochloride, labetalol hydrochloride, nicardipine hydrochloride, nilvadipine, nifedipine, diltiazem, nitrendipine, varnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine hydrochloride, alanidipine hydrochloride , Losartan potassium, candesartan cilexetil

  Vasoconstrictor: phenylephrine hydrochloride, pseudoephedrine, phenylpropanolamine hydrochloride

  Vasodilators: verapamil hydrochloride, cinnarizine

  Drugs for hyperlipidemia: cerivastatin sodium, simvastatin, pravastatin sodium, atorvastatin calcium hydrate, clofibrate

  Respiratory drug: Levalorphan tartrate

  Antitussive: Cloperastine, dextromethorphan hydrobromide

  Pesticides: ambroxol hydrochloride, bromhexine hydrochloride, L-carbocysteine

  Antitussive drug: potassium guaiacol sulfonate, guaifenesin, codeine phosphate, dihydrocodeine phosphate, methylephedrine hydrochloride, tipepidine hibenzate, trimethquinol hydrochloride, dextromethorphan phenolphthalein salt

  Bronchodilators: theophylline, salbutamol sulfate, oxyprenalin sulfate, methoxyphenamine hydrochloride, trimethquinol, procaterol, sodium montelukast

  Mouthwash: Azulene, povidone iodine

  Antidiarrheal / intestinal: loperamide hydrochloride, berberine, lactamine, spore-forming lactic acid bacteria, bifidobacteria, natto bacteria, butyric acid bacteria

  Anti-ulcer drugs: lansoprazole, omeprazole, rabeprazole, famotidine, cimetidine, ranitidine hydrochloride, sulpiride, deprenone, sucralfate

  Gastric digestives: Diastase, funnel extract, cellulase AP3, lipase AP, cinnamon oil

  Antacids: magnesium carbonate, sodium hydrogen carbonate, magnesium aluminate metasilicate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide

  Constipation medication: sennoside, sennoside calcium, bisacodyl, picosulfate sodium

  Antibacterial drugs: dehydrocholic acid, trepibutone

  Nourishing tonics: vitamin A, vitamin D, vitamin E (such as d-α-tocopherol acetate), vitamin B1 (such as dibenzoylthiamine, fursultiamine hydrochloride), vitamin B2 (such as riboflavin butyrate), vitamin B6 (hydrochloric acid) Vitamins such as pyridoxine), vitamin C (ascorbic acid, sodium L-ascorbate, etc.), vitamin B12 (hydroxocobalamin acetate, mecobalamin, cyanocobalamin, etc.), minerals such as calcium, magnesium, iron, proteins, amino acids, herbal medicines

  Gout treatments: allopurinol, colchicine

  Antidiabetic drugs: tolbutamide, glibenclamide, acarbose, voglibose, pioglitazone hydrochloride

  Antibiotics: cephalexin, cefaclor, amoxicillin, pipmecillin hydrochloride, cefotiam hexetyl, cefadroxyl, cefixime, cefditoren pivoxil, cefteram pivoxil, cefpodoximiproxetil, ampicillin, cyclacin, enoxacin, carmonam sodium

  Antibacterial drugs: Triclosan, cetylpyridinium chloride, domifene bromide, quaternary ammonium salt, zinc compound, sanguinarine, fluoride, alexidine, octonidin, EDTA, nalidixic acid, enoxacin, ofloxacin, sulfamethoxazole, trimethoprim

  Drugs for osteoporosis: ipriflavone, alendronate sodium

  Skeletal muscle relaxant: Metocarbamol

  Anti-rheumatic drugs: methotrexate, bucillamine

  Hormonal drugs: liothyronine sodium, dexamethasone sodium phosphate, prednisolone, oxendron, leuprorelin acetate, triamcinolone acetonide, hydrocortisone

  Alkaloid narcotics: opium, morphine hydrochloride, tocone, oxycodone hydrochloride, opium alkaloid hydrochloride, cocaine hydrochloride

  Anticoagulant: Dicoumarol

  Antineoplastic: 5-fluorouracil, uracil, mitomycin, manidipine hydrochloride, pioglitazone hydrochloride

  Parasympathetic blockade: Belladonna total alkaloids, datsura extract, homatropine, tropicamide, butyl scopolamine, mebenzolate

  Antihistamines, antiallergic drugs: chlorpheniramine maleate, carbinoxamine maleate, clemastine fumarate, diphenhydramine hydrochloride, diphenhydramine citrate, diphenylpyraline hydrochloride, promethazine hydrochloride, triprolidine hydrochloride, loratadine, mequitazine, amlexanox, seratrodast, cromoglycic acid Sodium, ketotifen fumarate, pranlukast hydrate, fexofenadine hydrochloride, bepotastine besylate, cetirizine hydrochloride, epinastine hydrochloride

  Erectile dysfunction drug: vardenafil hydrochloride hydrate, sildenafil hydrochloride, sildenafil citrate

  Other: Nicotine, nicotine resinate

The food ingredient used as the active ingredient is not particularly limited as long as it can be ingested by the film preparation. The food component may be in a solid or liquid state at room temperature.
Specific examples of food ingredients include fragrances, fruit juices, plant extracts, animal extracts, vitamins and the like.

  More specifically, menthol, lemon oil, peppermint, spearmint, perilla juice, coenzyme Q10, yellow aloe extract, Hypericum perforatum extract, Maria thistle extract, Ginkgo biloba leaf extract, red grape leaf extract, saw palmetto fruit extract, pumpkin seed extract, Atlantic carrot Examples include I extract, valerian extract, hop extract, rosehip extract, echinacea extract, ginger extract, garlic extract, DHA, EPA, lactoferrin extract, vitamins, amino acids, sardine peptides and the like.

Some of the above substances fall into both drugs and food ingredients due to their nature. In this case, the film containing the substance can be used as either a drug or a food ingredient depending on the purpose of use.
The active ingredients used in the present invention include known compounds and are readily available on the market or can be synthesized.
Moreover, an active ingredient can be used individually or in combination of 2 or more types.

  An active ingredient may give a bitter taste and / or an unpleasant taste to a film formulation by the kind and addition amount. When the film preparation is for oral administration, it is preferable to mask the bitter taste and / or unpleasant taste to remove the obstacle at the time of taking.

  Examples of active ingredients that give a bitter or unpleasant taste include fexofenadine hydrochloride, cetirizine hydrochloride, mequitazine, diphenhydramine hydrochloride, dextromethorphan hydrobromide, fluvoxamine maleate, phenylephrine hydrochloride, and the like.

  The masking technique applicable to the present invention is not particularly limited. However, a method using a masking agent is preferred from the viewpoint of taking advantage of the characteristics of a film preparation that is dissolved in the oral cavity and taken. Specific methods include inclusion with cyclodextrin, adsorption with an ion exchange resin, and microencapsulation (or micromatrix formation) using a hardly water-soluble substance.

  As the cyclodextrin as a masking agent, alpha-type, beta-type and gamma-type cyclodextrins can be used. The type of cyclodextrin can be appropriately selected based on the physicochemical properties (molecular weight and the like) of the active ingredient. Inclusion with cyclodextrin may be carried out in advance before the production of the active ingredient-containing layer, or by mixing simultaneously with other ingredients (active ingredient, water-soluble polymer and disintegrant) during the production of the active ingredient-containing layer. You may go.

As the ion exchange resin that is a masking agent, a cation exchange resin or an anion exchange resin can be used. Specific examples include AMBERLITE IRP69, IRP64, IRP88 and IRP43 manufactured by ROHM AND HASS FRANCE.
The type of the ion exchange resin can be appropriately selected based on the physicochemical properties (pH, etc.) of the active ingredient. Adsorption with an ion exchange resin may be performed in advance before the production of the active ingredient-containing layer, and is mixed simultaneously with other components (active ingredient, water-soluble polymer and disintegrant) during the production of the active ingredient-containing layer. May be performed.

  Examples of the poorly water-soluble substances that are masking agents include the aforementioned ion exchange resin, stearic acid, stearyl alcohol, hydrogenated oil, wax (eg carnauba wax), ethyl cellulose, acrylic polymer, polylactic acid, hydroxypropylmethylcellulose phthalate, polyvinyl acetal diethylaminoacetate. And carboxymethyl ethyl cellulose. The kind of the hardly water-soluble substance can be appropriately selected based on the physicochemical properties of the active ingredient (bitterness strength, solubility, pH, melting point, etc.).

  The microencapsulation (micromatrix formation) with a hardly water-soluble substance is preferably performed in advance before the production of the active ingredient-containing layer. Specifically, the microcapsule or the microphone matrix is formed by coating the active ingredient with a poorly water-soluble substance or kneading the active ingredient into the poorly water-soluble substance.

  As a forming method, a spray cooling method is preferable. The particle size (average particle size by laser diffraction / scattering method) of the microcapsules and the micromatrix is preferably 10 to 300 μm from the viewpoint that the film preparation does not feel rough when dissolved in the oral cavity.

It is a top view of the oral film formulation which has a safety valve of 1st Embodiment of this invention. It is a top view of the oral film formulation which has a safety valve of 2nd Embodiment of this invention. It is a top view of the oral film formulation which has a safety valve of 3rd Embodiment of this invention. It is a top view of the oral film formulation which has a safety valve of 4th Embodiment of this invention. It is a top view of the oral film formulation which has a safety valve of 5th Embodiment of this invention. It is a top view of the oral film formulation which has a safety valve of a 1st comparative example. It is a top view of the oral film formulation which has a safety valve of a 2nd comparative example. It is a top view of the oral film formulation which has a safety valve of a 3rd comparative example. It is a top view of the oral film formulation which has a safety valve of a 4th comparative example. It is a top view of the oral film formulation which has a safety valve of a 5th comparative example. It is a top view of the oral film formulation which has a safety valve of a 6th comparative example. It is a top view of the oral film formulation which has a safety valve of a 7th comparative example. It is a top view of the oral film formulation which has a safety valve of an 8th comparative example. It is a description perspective view of the opening area measuring apparatus for intake.

(First embodiment)
(1) The oral film preparation 10 is a film preparation having a two-layer structure composed of one active ingredient-containing layer and one active ingredient-free layer. In this specification, the amount of substance is shown on a dry product basis.
(2) Production of active ingredient-free layer Hydroxypropyl methylcellulose as water-soluble polymer (methoxyl group content 28-30%, hydroxypropoxyl group content 7-12%, kinematic viscosity 12.5-17.5 mm ² / s ) (Manufactured by Shin-Etsu Chemical Co., Ltd., trade name: TC-5S) 10.0 g of concentrated glycerin as a plasticizer was dissolved in 90 ml of purified water as a solvent to prepare a solution.
The resulting solution was spread on a polyethylene terephthalate film-forming form using a baker applicator (Imoto Seisakusho Co., Ltd.). The solvent was removed by air drying at 60 ° C. to form a film.

(3) Production of Active Component-Containing Layer 6.0 g of d-chlorpheniramine maleate and 0.6 g of belladonna alkaloid as active components, hydroxypropyl methylcellulose as a water-soluble polymer (methoxyl group content 28.0 to 30.0) %, Hydroxypropoxyl group content 7.0 to 12.0%, kinematic viscosity 2.5 to 3.5 mm ² / s) (manufactured by Shin-Etsu Chemical Co., Ltd., trade name: HPMTC TC- 5E) 30.0 g, 12.0 g sucrose fatty acid ester as emulsifier, 3.0 g acesulfame potassium as sweetener and 3.0 g aspartame, 6.6 g L-menthol as taste-masking agent, concentrated glycerin 18 as plasticizer 0.0 g and a mixture of crystalline cellulose and sodium carboxymethyl cellulose as a non-aqueous foaming disintegrant (mixing ratio (mass basis) 80:20), kinematic viscosity 30-100 mPa · s) (Asahi Kasei Chemicals Co., Ltd., trade name: Theolas RC-A591NF) A solution was made by dissolving in 0.0 g.
The obtained solution was spread on a mold on which an active ingredient non-containing layer was formed using a baker applicator (manufactured by Imoto Seisakusho Co., Ltd.). The solvent was removed by air drying at 60 ° C. to form a film.

(4) The formed film was peeled off from the formwork, cut, and as shown in FIG. 1, the short side was 20.0 mm, the long side was 30.0 mm, and the thickness was 0.14 mm (active ingredient-containing layer: 0.0. A rectangular film preparation 10 having a thickness of 13 mm and an active ingredient non-containing layer: 0.01 mm was obtained. An elliptical arc cut 12 having an elliptical arc shape with a minor axis of 6 mm and a width of 0 mm was made at the center of the film preparation 10.

(Second Embodiment)
As shown in FIG. 2, a semi-elliptical shape having a minor axis of 6 mm and an elliptical arc cut 22 having a width of 0 mm are vertically oriented in the same direction at the center of the same film preparation 20 as the film preparation 10 of the first embodiment. I put them.

(Third embodiment)
As shown in FIG. 3, an elliptical arc notch 22 having a minor axis of 6 mm and a width of 0 mm is vertically oriented in the center of the same film formulation 30 as the film formulation 10 of the first embodiment. Two were put.

(Fourth embodiment)
As shown in FIG. 4, an elliptical arc cut 42 having a minor axis of 6.0 mm and a width of 0.25 mm was formed in the center of the same film formulation 40 as the film formulation 10 of the first embodiment.

(Fifth embodiment)
As shown in FIG. 5, an elliptical arc cut 52 having a minor axis of 6 mm and a width of 0 mm is inserted in the central portion of the same film formulation 5 as the film formulation 10 of the first embodiment. The cut was cut by 0.1 mm.

(First comparative example)
As shown in FIG. 6, an elliptical arc cut 112 having a minor axis of 4 mm and a width of 0 mm was vertically placed in the center of the same film formulation 110 as the film formulation 10 of the first embodiment.

(Second comparative example)
As shown in FIG. 7, an elliptical arc cut 112 having a minor axis of 6 mm and a width of 0 mm was vertically formed in the center of the same film formulation 120 as the film formulation 10 of the first embodiment. Further, a transverse cut 114 extending from the left end of the elliptical arc cut 112 to the left edge of the film preparation 120 was made.

(Third comparative example)
As shown in FIG. 8, an elliptical arc cut 132 having a minor axis of 6 mm and a width of 0 mm is vertically placed in the central part of the same film formulation 130 as the film formulation 10 of the first embodiment. A 1 mm cut was cut at the center.

(Fourth comparative example)
As shown in FIG. 9, a transverse notch 142 having a length of 3 mm and a width of 0 mm reaching the left and right edges of the film formulation 20 was inserted in the central part of the same film formulation 140 as the film formulation 10 of the first embodiment.

(Fifth comparative example)
As shown in FIG. 10, an elliptical arc notch 152 having a major axis of 4 mm and a width of 0 mm is placed in the center of the same film formulation 150 as the film formulation 10 of the first embodiment. I put them.

(Sixth comparative example)
As shown in FIG. 11, an elliptical arc-shaped hole having a minor axis of 6 mm was provided at the center of the same film preparation 160 as the film preparation 10 of the first embodiment.

(Seventh comparative example)
As shown in FIG. 12, an incision 172 having a short diameter of 6 mm and a width of 2 mm was provided at the center of the same film preparation 170 as the film preparation 10 of the first embodiment.

(Eighth comparative example)
As shown in FIG. 13, a circular hole 182 having a radius of 3 mm was provided at the center of the same film preparation 180 as the film preparation 10 of the first embodiment.

(Evaluation of embodiment and comparative example)
The strength and inhalation opening area of the film preparations of the above-described embodiments and comparative examples were measured.
The strength was measured by using a spring-type hand balance (Sanko Seisakusho Co., Ltd. 1 kg) and measuring the tensile strength (g). The strength of the film preparation was evaluated according to the following criteria based on the tensile strength of the film preparation.
○ Strength: 500g or more
X No strength: Strength is lower than 500 g

The opening area for intake was measured by the intake test. As shown in FIG. 14, an intake opening area measuring apparatus 200 is provided with a vacuum pump (YAMATO MINIVAC, Yamato Science Co., Ltd.) on a plate 204 having a length of 200 mm, a width of 150 mm, and a thickness of 5 mm. PD-136) is used to attach a hose 206 having a diameter of 100 mm with the intake air amount from the intake hole 202 set to 30 L / min.

  In the measurement, a film preparation (not shown) is placed on the plate 204 so that a cut or the like at the center of the film preparation is on the intake hole 202, and the open area of the film preparation 10 at the time of inhalation is measured. did. The open area of the film preparation 10 at the time of inhalation was evaluated according to the following criteria based on a commercially available troche having a diameter of 15 mm or more.

The outer diameter of commercially available troches with a diameter of 15 mm or more is 6 mm, the area is 28.3 mm ² , and the shape of New Tonin Troche L (Sato Pharmaceutical) is 18 mm in outer diameter, 6 mm in inner diameter, Cool One throat troche ( Sato Pharmaceutical Co., Ltd. Shape: outer diameter 18 mm, inner diameter 6 mm.
○ Open area sufficient to secure the airway: Open area is 28.3 mm ² or more
× Open area not enough to secure the airway: Open area is less than 28.3 mm ²

The measurement results are as shown in Table 1.

  From the measurement results shown in Table 1, Embodiments 1 to 5 show that both strength and inhalation opening area are compatible with strength as a film preparation and safety when the airway is blocked.

Claims (8)

An oral film preparation having a safety valve, which is a film preparation having a minimum delivery length of 15 mm or more and an area of 175 mm ² or more, which is provided with a valve notch that does not extend to the periphery.   The oral film preparation having a safety valve according to claim 1, wherein a width of the cut for the valve is 1 mm or less.   The oral film preparation having a safety valve according to claim 1, wherein the valve cut is intermittent.   The oral film preparation having a safety valve according to claim 1, wherein the incision for the valve has an arc shape, an elliptical arc shape, or a U-shape. The oral film preparation having a safety valve according to claim 1, wherein an area of a hole formed when the valve cut is opened is 25 mm ² or more. The film preparation comprises an active ingredient-containing layer containing an active ingredient, a water-soluble polymer selected from the group consisting of methylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose, and a disintegrant.
An active ingredient-free layer containing methylcellulose and / or hydroxypropylmethylcellulose,
The amount of the active ingredient is 0.1% by mass to 75.0% by mass of the total mass of the film preparation,
The total amount of the active ingredient and the water-soluble polymer in the active ingredient-containing layer is 15.0 mass% to 95.0 mass% of the total mass of the active ingredient-containing layer. An oral film preparation having the safety valve described.   The film preparation is a film preparation comprising an active ingredient-containing layer containing an active ingredient, hydroxypropylmethylcellulose and a disintegrant, and an active ingredient-free layer containing hydroxypropylmethylcellulose, the disintegrant The film preparation having a safety valve according to claim 1, wherein is a mixture of crystalline cellulose and sodium carboxymethylcellulose.   The oral film preparation having a safety valve according to claim 1, wherein the film preparation is a colloidal grade mixture of crystalline cellulose and sodium carboxymethylcellulose.

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