KR101781071B1 - Composition for orally rapid disintegrating film of local anesthesia - Google Patents
Composition for orally rapid disintegrating film of local anesthesia Download PDFInfo
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- KR101781071B1 KR101781071B1 KR1020150112907A KR20150112907A KR101781071B1 KR 101781071 B1 KR101781071 B1 KR 101781071B1 KR 1020150112907 A KR1020150112907 A KR 1020150112907A KR 20150112907 A KR20150112907 A KR 20150112907A KR 101781071 B1 KR101781071 B1 KR 101781071B1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0063—Periodont
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Abstract
The present invention relates to an oral disintegrating film composition comprising a local anesthetic agent, wherein the oral disintegrative film is an oral disintegrating film which can be used for gum pain, pain relief from stomatitis, and dental anesthesia, The pain of the patient can be avoided and a quick anesthetic effect can be obtained, and the convenience of the patient and compliance with the medication can be improved.
Description
The present invention relates to an oral disintegrating film composition containing a local anesthetic.
Many current oral medicines are mainly composed of tablets, capsules, syrups, and the like. However, children and older people often have difficulty taking tablets (Sabar M. H., 2013). Recently, formulations in the form of orally disintegrating film (ODF) have been developed to overcome the inconvenience of tablets administration.
Oral disintegration film refers to a thin film that can undergo rapid disintegration when contacted with saliva in the oral cavity (Panda B. P. et al., 2012). These oral disintegration films have the advantage of being able to take precise doses and convenient doses to increase patient compliance (Jyoti A. et al., 2011). Further, while tablets are fragile, the oral disintegration film is a more stable, well tolerated ready-to-use formulation, flexible and portable. In the case of liquid oral preparations, the dose to be measured varies depending on the person to be administered, but in the case of the oral disintegration film, the dosage is accurately determined because it is prepared so as to contain the exact amount of the drug.
In addition, all oral preparations, such as tablets, are required to take more drugs because they are affected by stomach acid, bile, digestive enzymes, etc. before they enter the blood stream. However, since the oral disintegration film transmits the active agent through the mucosa, It has an advantage that it can prevent not only poor absorption or inactivation through pathway but also primary metabolism by the liver.
Currently available film formulations include asthma treatment, erectile dysfunction, oral cleansing, areas accompanied by cancer patients receiving chemotherapy, and vomiting prevention.
Local anesthetics are drugs that act on the peripheral sensory nerve to block neurotransmission, thereby slowing or eliminating the localized nociception. Clinically, local anesthetics are used in dentistry to alleviate toothache and local anesthesia before excretion, and in the surgical field for local anesthesia during simple surgical procedures (Becker D. E. et al., 2012). Representative examples of topical anesthetic agents include cocaine, benzocaine, lidocaine, bupivacaine, tetracaine, procaine, etidocaine, and the like. (McLure HA et al., 71, 59-74, 2005).
Although most of the formulations of local anesthetics have been developed as injections (McLure H. A. et al., 71, 59-74, 2005), injections have the advantage of being faster, but there is a fear of systemic side effects due to a rapid rise in blood levels. In addition, pediatric patients and some adults avoid avoiding injections due to fear of injection, and topical application formulations such as ointments and gels have been developed and marketed to solve these problems.
Recently, a patch agent containing lidocaine, one of the local anesthetics, has been developed, and the patch agent is intended for skin attachment. However, patches are troublesome to be removed after drug release, and there is a limit to exhibit systemic side effects due to difficulty in controlling the dose during the time required for the administration of an anesthetic effect.
Korean Patent Publication No. 2006-0115766 discloses a slow dissolving film composition for use in the delivery of topical and / or systemic active substances. Korean Patent Laid-Open Nos. 2001-0015631 and 2007-0007299 disclose a rapid dissolution film for the delivery of active agents to wetted body surfaces, and the elution times of the active agents are 24 hours and 10 minutes, respectively. Korean Patent Laid-Open Publication No. 2013-0112413 discloses a percutaneous absorption preparation containing lidocaine or a salt thereof, and Korean Patent No. 0843001 discloses an oral mucoadhesive film preparation.
Accordingly, the inventors of the present invention have developed a formulation capable of exhibiting the effects of rapid pain relieving action and action, as desired. As a result, it has been found that the dissolution rate of the drug is within 1 minute, and the portability is easy, The present invention can be completed by developing a film formulation.
It is an object of the present invention to provide a composition of an oral disintegrating film containing a local anesthetic agent and to provide an oral disintegrating film composition capable of safely localizing anesthesia by rapidly dissolving a local anesthetic agent in the oral cavity and eluting it into a film .
I) a topical anesthetic; ii) sodium alginate; iii) hydroxypropylmethylcellulose; And iv) polyvinylpyrrolidone; And more than 90% of the local anesthetic is eluted within one minute.
The oral disintegration film composition comprises i) 100 parts by weight of a local anesthetic; ii) 50 to 70 parts by weight of sodium alginate; iii) 35 to 55 parts by weight of hydroxypropyl methylcellulose; And iv) 3.5 to 5.5 parts by weight of polyvinylpyrrolidone; ≪ / RTI >
The present invention also relates to an oral disintegration film made from the oral disintegrating film composition.
Hereinafter, the present invention will be described in detail.
I) a topical anesthetic; ii) sodium alginate; iii) hydroxypropylmethylcellulose; And iv) polyvinylpyrrolidone; And more than 90% of the local anesthetic is eluted within one minute.
The present invention also relates to a pharmaceutical composition comprising i) 100 parts by weight of a local anesthetic agent; ii) 50 to 70 parts by weight of sodium alginate; iii) 35 to 55 parts by weight of hydroxypropyl methylcellulose; And iv) 3.5 to 5.5 parts by weight of polyvinylpyrrolidone; ≪ / RTI >
Wherein the topical anesthetic agent is at least one selected from the group consisting of cocaine, benzocaine, procaine, tetracaine, propoxycaine, 2-chloroprocaine, lidocaine, bupivacaine, mephibacaine, , Preferably lidocaine and its salts.
The sodium alginate and hydroxypropylmethyl cellulose may improve the production, durability and stability of the film form. Also, polyvinylpyrrolidone can be mixed with hydroxypropyl methylcellulose to make the film transparent and fast to have disintegration.
The oral disintegration film may comprise glycerin and sodium lauryl sulfate as further components. At this time, based on 100 parts by weight of the local anesthetic agent, glycerin may include 20 to 40 parts by weight, and sodium lauryl sulfate may include 3.5 to 5.5 parts by weight.
The glycerin can control the viscosity of the oral disintegrating film composition. The viscosity of the oral disintegration film composition may be preferably from 13,800 cp to 29,154 cp at 21.5 캜.
The present invention also relates to an oral disintegration film made from the oral disintegrating film composition, wherein the oral disintegrative film can exhibit a strong anesthetic effect in a short time by eluting a local anesthetic agent of 90% or more within 1 minute.
Oral disintegration film can also be used for dental treatment. Preferably gum pain, pain relief from stomatitis, and dental local anesthetics.
The present invention relates to an oral disintegrating film composition comprising a local anesthetic agent, wherein the oral disintegrative film is an oral disintegrating film which can be used for gum pain, pain relief from stomatitis, and dental anesthesia, The pain of the patient can be avoided, and the convenience of the patient and compliance with medicines can be improved.
Figure 1 shows the dissolution rate of lidocain in the oral disintegration film of the present invention with time.
Fig. 2 shows X-ray diffraction results of lidocaine hydrochloride powder (A), lidocain-free film (B) and lidocaine-containing film (C). The X axis represents the incident angle of the X-ray, and the Y axis represents the intensity of diffraction.
Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.
≪ Example 1: Local anesthesia >
Each component was mixed under the conditions shown in Table 1 below to prepare an oral disintegrating film of the present invention.
Lidocaine was dissolved in 20 ml of water. In addition, sodium alginate was added to 80 ml of water, and the mixture was stirred until it became a gel phase. Hydroxypropyl methylcellulose, glycerin, polyvinyl pyrrolidone and sodium lauryl sulfate were added to sodium alginate gel, and mixed using a medical stirrer for 30 minutes. Respectively. The lidocain dissolved in water was added to the mixture, mixed again, and the bubbles were removed to prepare a drug. After constant casting of the drug on the polyethylene liner, it was dried in a desiccator for 2 hours. After drying, the film was peeled off to prepare a final film having a thickness of 0.05 占 0.01 cm, a size of 2 占 3 cm, and a weight of 40 mg / strip.
≪ Comparative Example 1 > Preparation of comparative mouth rinse solution film &
Each of the components was mixed under the conditions shown in Table 2 below to prepare a comparative mouth rinse solution film. The production process was carried out in the same manner as in Example 1.
Methyl cellulose
< Experimental Example One. Oral disintegration film Physical Characteristic Analysis>
Experimental Example 1-1. Tensile strength measurement
Three tensile strength films were prepared for each of the three samples of the oral disintegration film prepared in Example 1 and Comparative Example 1. Tensile Strength The tester was lowered at a constant speed with a tester to measure the strength when the film was torn by disintegration, and the results are shown in Table 3.
As shown in Table 3, it was found that the tensile strength of Example 1-3 was the largest.
Experimental Example 1-2. Thickness measurement
The mouth rusting film prepared in Example 1 was measured for four film thicknesses per each sample. The thickness was measured using a Vernier caliper. The thickness of each film is shown in Table 4.
Referring to Table 4, it can be seen that the thickness of the oral disintegration film produced in Example 1 is maintained at a constant thickness of 0.05 mm.
<Experimental Example 2> Content analysis of oral disintegration film>
The content of lidocain contained in the film was measured using an ultraviolet absorption spectrum using the oral disintegration film of Example 1-3. As a result, it was confirmed that 16 mg of lidocaine was contained per film (40 mg / strip).
< Experimental Example 3. Oral disintegration film Dissolution Test>
Dissolution tests of lidocaine were carried out using the oral disintegration films of Examples 1-3, 1-4 and Comparative Example 1. [
30 mL of water was put into a mouth-shaking film, stirred at a constant speed of 200 rpm, and the solution was collected at intervals of 1 minute, 3 minutes, 5 minutes, and 10 minutes, and absorbance was measured through ultraviolet absorption spectrum. The dissolution rate of lidocaine was measured using the measured absorbance. Each test was repeated 3 times. The experimental results are shown in Table 5 and Fig.
As shown in Table 5 and FIG. 1, 90% or more of lidocaine was eluted within 1 minute in the oral disintegration film of Examples 1-3 and 1-4.
<Experimental Example 4> Examination of ingredients of oral disintegration film>
X-ray diffraction analysis was performed using the oral disintegration film of Examples 1-3 in order to identify the lidocaine components present in the oral disintegration film of the present invention.
X-ray diffraction was analyzed using an X-ray diffractometer with lidocaine hydrochloride powder, lidocain-free film and lidocaine-containing film, and the results are shown in Fig.
As shown in Fig. 2, it was confirmed that lidocaine crystals exist intact in the lidocaine-containing film (Fig. 2C).
Claims (8)
ii) sodium alginate;
iii) hydroxypropylmethylcellulose; And
iv) polyvinylpyrrolidone;
Wherein at least 90% of the lidocaine and its salts are eluted within 1 minute.
i) 100 parts by weight of lidocaine and its salt;
ii) 50 to 70 parts by weight of sodium alginate;
iii) 35 to 55 parts by weight of hydroxypropyl methylcellulose; And
iv) 3.5 to 5.5 parts by weight of polyvinylpyrrolidone;
≪ / RTI >
Wherein said oral disintegration film comprises glycerin and sodium lauryl sulfate as further components.
Wherein the oral disintegration film contains 20 to 40 parts by weight of glycerin and 3.5 to 5.5 parts by weight of sodium lauryl sulfate based on 100 parts by weight of lidocaine and its salt.
Wherein said oral disintegration film is used as a topical anesthetic for dental and pain relief from gum pain, stomatitis, and oral disintegration film.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150112907A KR101781071B1 (en) | 2015-08-11 | 2015-08-11 | Composition for orally rapid disintegrating film of local anesthesia |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150112907A KR101781071B1 (en) | 2015-08-11 | 2015-08-11 | Composition for orally rapid disintegrating film of local anesthesia |
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| Publication Number | Publication Date |
|---|---|
| KR20170019055A KR20170019055A (en) | 2017-02-21 |
| KR101781071B1 true KR101781071B1 (en) | 2017-09-22 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020150112907A KR101781071B1 (en) | 2015-08-11 | 2015-08-11 | Composition for orally rapid disintegrating film of local anesthesia |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100375065B1 (en) | 2001-03-26 | 2003-03-07 | 엘지산전 주식회사 | Apparatus for data store of memory circuit |
| KR100843001B1 (en) | 2002-01-16 | 2008-07-01 | 동화약품공업주식회사 | Oral Mucoadhesive Film |
| RU2380092C2 (en) | 2004-01-30 | 2010-01-27 | Кориум Интернэшнл, Инк. | Rapidly dissolved film for active agent delivery |
| BRPI0508359A (en) | 2004-03-03 | 2007-09-25 | Warner Lambert Co | film compositions |
| KR20130112413A (en) | 2012-04-04 | 2013-10-14 | 조선대학교산학협력단 | Transdermal formulation comprising lidocaine or its salt and prilocaine or its salt |
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| KR20170019055A (en) | 2017-02-21 |
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