WO2013015545A1 - Composition for edible film and pharmaceutical preparation for edible film containing drugs - Google Patents

Abstract

This invention relates to composition for film with improved physical properties of edible film and its pharmaceutical preparation for film. This invention provides us with composition for edible film, which consists of hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) and pharmaceutical preparation for edible film containing drugs. Composition for edible film according to this invention enables us to manufacture intended edible film regardless of adding excipients in order to improve physical properties of film. Also, it has high performance on its physical properties, and enables us to manufacture edible film with high dissolution rate in the oral cavity. Furthermore, pharmaceutical preparation for edible film inhibits limitation on contents of drugs due to excipients, and enables us to manufacture pharmaceutical preparation for edible film containing various drugs without improving physical properties by using other excipients, and improves dosage compliance and convenience for various drugs.

Description

COMPOSITION FOR EDIBLE FILM AND PHARMACEUTICAL PREPARATION FOR EDIBLE FILM CONTAINING DRUGS

This invention relates to composition for film, which improves physical properties of edible film and pharmaceutical preparation for film containing drugs.

A pharmaceutical preparation exists in various ways at present pharmaceutical field. For example, these dosage forms are designed to be swallowed with suitable volume of water in order to deliver drugs. In addition, as liquid form, suspension concentrate and injections are administered orally or in a non-oral manner.

However, recently there is difficulty in chewing or swallowing solid-type medication for the children, the old-aged, and those who reject taking medication. Many patients are reluctant to take these medications due to the fact that even though solid dosage form or liquid is used as an administration unit of dose, activating medicine is difficult to be swallowed or it can be stuck in gula or esophagus. In addition, while the drug is administered, the use of drinking water can be limited for specific patients and for specific disease and/or treatment.

Eventually, recent various ongoing researches caused the advent of dosage form having new drug transmission system. Orally disintegrated tablet (ODT) which was developed from solid dosage form to disintegrated configuration in oral cavity is one of these products. However, even although orally disintegrated tablet (ODT) also dissolve drug in the oral cavity, every drug is not disintegrated in general. Even it is common that it involves drinking water again.

Dosage form, which newly suggests medicine delivery system, is pharmaceutical preparation for edible film which often mentioned recently. It also provides us with some advantages over solid formulation, liquid, and orally disintegrated tablet.

The dosage form of film which recently is researched has more improved feature than any other pharmaceutical type which previously existed, based on concept that drug is disintegrated. Further, there are many trials manufacturing composition for edible film with various techniques in order to improve physical properties of film and patients` drug adherence.

Research on film-forming polymer for forming film is the most significant part in film composition technique, and many researchers carry out their ongoing researches on polymer forming edible film. However, in some cases of polymer, it displays its various physical properties, depending on its intrinsic physical property if drug is injected.

At present, commercialized polymers as a film former for manufacturing composite of edible film, are various polymers such as pullulan, gelatin, pectin, low-viscosity pectin, hydroxypropyl methylcellulose, low-viscosity hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol, polyacryllic acid, methyl methacrylate copolymer, carboxyvinylpolymer, polyvinylethylene glycol, alginic acid, low-viscosity alginic acid, sodium alginate, modified starch, casein, whey protein isolates, soy protein isolates, zein, levan, elsinan, gluten, acacia gum, carrageenan, arabic gum, guar gum, locust bean gum, xathan gum, gellan gum, and agar. Furthermore, manufacturing film-type pharmaceutical preparation using these polymers is well known before.

However, this pharmaceutical preparation for edible film as in the past is not a basic substance which consists of drugs or polymer itself, but there is cumbersomeness that it demands improving physical properties of film due to the mixture of drug and polymers.

In order to solve the problem described as above, in Korean patent application Nos. 2007-0080677, 2008-0026953, 2005-7014063, 2010-7017866, 2010-7027980, 2009-0085522, 2002-7000868, 2008-7014544, and 2001-7009145, edible film with improved property of film by raising the strength and tensile strength of film is disclosed. However, there are many cases that it film is formed by adding excipients such as stabilizer, softener, and plasticizer in order to improve physical properties due to the fact that the property of film is not improved by film-forming agents.

Even though those polymers are used by adding many excipients for forming this film as above, there is still limited receptive capacity for raw material and/or drug. Thus, there is the limitation on efficacy or effectiveness resulted from intake of it.

In fact, even though the oral dosage form of film containing raw material and/or drugs includes acceptable drug as well as physical properties such as the strength and flexibility of film, it should not give any effect on physical properties in order to be used as medicine beneficial to human body after intake of it

Accordingly, pharmaceutical preparation for edible film requires compatibility between film and drugs physically in addition to its physical property of film. However, in case of pharmaceutical preparation for film which has been used previously, film forming polymers are used as single polymer, and consequently physical properties of film are improved by adding various excipients.

There have been repeated researches on film forming agents improving the physical properties of polymer itself forming film and improving film formation and physical property even in case of using it with drug. Homogeneously mixed composition of two specific film forming polymers was used as an edible film forming agent. In addition, high functioning polymer composition for edible film with improved physical properties (strength, tensile strength, and dissolution rate in the oral cavity) regardless of adding excipients was used. Accordingly, pharmaceutical preparation for film containing drugs was developed by using polymer compositions for edible film described as above, and this invention was completed.

The purpose of the present invention is to provide us with composition for edible film with improved physical property for the dosage form of edible film regardless of using excipients improving physical properties of film itself.

Another purpose regarding the present invention is to provide us with pharmaceutical preparation for edible film containing drugs.

Detailed explanation which relates to invention is described as below.

The present invention provides us with composition for edible film consisting of hyroxypropyl methylcellulose and polyvinyl alcohol-polyethylene glycol graft copolymer, PVA-PEG copolymer) with improved physical properties of film for edible film.

According to the present invention, composition for edible film consisting of hyroxypropyl methylcellulose and polyvinyl alcohol-polyethylene glycol graft copolymer, PVA-PEG copolymer) can be mixed in the weight (w/w %) ratio of 95:5~5:95. Also, 95:5~30:70 w/w % is preferable, and 50:50 is more preferable.

Surprisingly, according to the present invention, composition consisting of hyroxypropyl methylcellulose and polyvinyl alcohol-polyethylene glycol graft copolymer, PVA-PEG copolymer), gives better effect than other single polymer or its mixed composition known widely as edible film former in physical properties that film formers should have, that is, strength, tensile strength, and dissolution rate in the oral cavity.

Regardless of adding excipients to improve the physical property of film, this invention enables us to manufacture the intended pharmaceutical preparation for edible film without any limitation on types and contents of drug. Also, it helps us to inhibit adding excipients (stabilizer, softener, and plasticizer) used previously to improve physical properties of film.

According to the present invention, composition for film can be manufactured by mixing hydroxpropyl methylcellulose(HPMC) with Polyvinyl alcohol-polyethylene glycol copolymer in suitable volume of purified water and dissolving them thoroughly. Edible film can be manufactured with composition for film described as above by using film coating machine and casting them in stainless steel molder.

In addition, the present invention provides us with pharmaceutical preparation manufactured by adding drugs to composition for film described as above.

The present invention is not limited to any type of drugs which are contained in pharmaceutical preparation for edible film, and its molecular weight 100 to 600(g/ mol) is preferred due to the fact that even though any type of drugs are added, it does not give any effect on the physical properties of edible film.

Pharmaceutical preparation for edible film containing drugs according to the present invention can be manufactured by using film coating machine and casting it in stainless steel molder after drug is dissolved in suitable volume of purified water thoroughly, and composition for film is mixed with it and is dissolved in it.

In the present invention, it can be manufactured by adding pharmaceutically acceptable flavor improvement agents which are used for typical pharmaceutical preparation for film, and one or more can be selected from the group consisting of L-menthol, strawberry flavor, lemon flavor, pineapple flavor, acesulfame potassium, aspartame, sucralose or citric acid.

The present invention enables us to manufacture intended edible film regardless of adding excipients to improve physical properties of film by providing composition for edible film, which consists of hydroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG Copolymer) Also, its physical properties of film have high functionality, and it enables us to manufacture edible film with high dissolution rate in the oral cavity.

In addition, the present invention inhibits limitation on the contents of drug and enables us to intended manufacture pharmaceutical preparation for edible film. Also, it can be used for manufacturing pharmaceutical preparation for edible film containing various types of drugs, and improves dosage compliancy and convenience for various drugs.

<Example 1> manufacture of edible film by composition for film of the present invention

30g of composition for film (component ratio =50:50, w/w%), which is a mixture of 15g of hyroxypropyl methylcellulose (HPMC) and 15g of polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG copolymer), is added into suitable volume of purified water. After it is dissolved thoroughly by stirring at 2,000 rpm for one hour by using a homogenizer, it is left for 24 hours at room temperature. Then, the solution described as above is casted in stainless steel molder by using film coating machine. Homogenized film with width of 200㎛ is manufactured after letting it dry out at 80^oC

<Contrast Example 1> manufacture of edible film by using HPMC and plasticizer

ZUPLENZ^® (manufacturer : Par Pharmaceutical, Inc.) is a product approved by US FDA currently, wherein HPMC is used as edible film-forming agent, and edible film manufactured by using HPMC and plasticizer are presented as contrast example 1.

Edible film is manufactured by using the same method as Example 1 of the present invention by mixing 30g of HPMC polymer with 1.8g of polyethylene oxide as a plasticizer in suitable volume of purified water.

<Contrast Example 2> manufacture of edible film by using pullulan material and plasticizer

Pullulan is disclosed as an edible film-forming agent in Korean Patent Application No. 2002-7000868, and edible film comprising pullulan and plasticizer is manufactured presented in contrast example 2.

Edible film is manufactured by mixing 30g of pullulan polymer with 2g of glycerin as a plasticizer in suitable volume of purified water by using the same method as example 1.

<Comparative Examples 1 to 5> manufacture of edible film by using single polymer

Edible film is manufactured by mixing each 30g of Hyroxypropyl methylcellulose, Hydroxy propyl cellulose, Pullulan, Polyvinylpyrrolidone (PVP) and Polyvinyl alcohol-Polyethylene glycol copolymer disclosed as edible film-forming agent in the table shown as below with suitable volume of purified water in the same method as example 1, represented as comparative examples 1 to 5.

Table 1

<Comparative Examples 6 to 14> manufacture of edible film by using polymer mixed composition

After adding 30g of polymer composition specified in the table shown as below into suitable volume of purified water, and mix them with it, the edible film is manufactured and presented as comparative examples 6 to 14.

Table 2

<Experimental Example 1> test comparing physical properties of edible film and dissolution rate in the oral cavity

They are tests intended for comparing physical properties and dissolution rate in the oral cavity films manufactured in example 1 as above (edible film by composition for edible film of this invention), comparative example 1 to 5 (edible film by single polymer), comparative example 6 to 14 (edible film by mixed composition of polymers), and example of contrast 1, 2(edible film by single polymer using plasticizer).

1) Tensile strength test

The purpose of tensile strength test is to compare physical properties of edible films by the strength of edible film and elongation.

Specimen of film manufactured in example 1 presented as above, comparative example 1 to 5, comparative example 6 to 14, and contrast example 1 and 2 (specimen size standard: ASTM D638 type IV) were measured (measurement condition: Cross head speed -10mm/min) for strength and elongation of film by using tensile machine(AG-5000g Shimadzu, Japan).

Elongation through tensile experiment is calculated by using formula presented as below.

Elongation, % = (△L -L)/L X 10

△L : elongated length of specimen

L: initial length of specimen

2) Flexibility test

This is a test verifying flexibility of edible film. Film, manufactured in example 1 presented as above, comparative example 1 to 5, comparative example 6 to 14, and example of contrast 1 and 2 , is inserted to dryer ( 80^oC, 2 hours) Then, its angle is measured when film described as above is folded in half after water in film is removed thoroughly.

3) Test comparing dissolution rate in the oral cavity

The purpose of this test is to know the dissolution rate of edible film in the oral cavity. Edible film, manufactured in example 1, comparative example1 to 5, comparative example 6 to 14, and contrast example 1 and 2, is inserted into the oral cavity of five adults. Then, time elapsed until it is thoroughly dissolved is measured, its average value is calculated.

4) Test Result

Test result which relates to measured tensile strength( strength of film, elongation) , flexibility, and dissolution rate in the oral cavity of edible film manufactured in example 1, comparative example1 to 5, comparative example 6 to 14, and contrast example 1 and 2, is presented in Table 3.

Table 3

5) Assessment

As it is known in Table 3 presented as above, among edible film (comparative example 1 to 5) formed by film-forming agents of single polymer, relatively high dissolution rate is measured in comparative example 1 and 2, and edible film has the physical property that it can contain drugs. However, it is not satisfactory in strength, elongation, and flexibility of film. In case of comparative example 3 and 4, film strength, elongation, flexibility, and dissolution rate in the oral cavity were low. On the other hand, the result showed its high flexibility and dissolution rate in the oral cavity in comparative example 5, but it indicated low strength of film therein.

Furthermore, among edible films formed by a mixture of polymers (comparative example 6 to 14), dissolution rate in the oral cavity was satisfactory, but film strength, elongation, and flexibility were low. In case of comparison 7 to 10 and 12, film strength, elongation, flexibility, and dissolution rate in the oral cavity were all low. In case of comparison 13, its flexibility was high, but film strength, elongation, and dissolution rate in the oral cavity were low. In comparative example 11 and 14, it was impossible to manufacture film due to the phase separation of solution.

Especially, in comparison 1 to 4, comparison 6 to 10 and 12, there is significantly low flexibility due to the fact that it was broken immediately when force is exerted to it for measuring flexibility. Also, low strength in comparison 5 and 13, means that the dosage forms of film can be broken even though significantly low force is exerted after film is formed, and it does not have any function as a dosage form when it is exposed to the vertical force.

In addition, in case of comparative example 1 and 2, strength, elongation, flexibility and dissolution rate in the oral cavity were relatively high. However, in case of comparative examples 1 to 14, it is known that it was not appropriate to manufacture film by using single polymer or by mixing polymers, and it was used after the physical properties of film-forming single polymer were improved by adding other excipients (plasticizer, softer, and thickener).

Surprisingly, composition for film in example 1 according to the present invention provided us with unexpected results contrary to the physical properties of edible film by prior art. That is to say, it is indicated that among composition of several polymers, which are film-forming agents, composition for edible film, which consists of hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol copolymer, gives significant effect on strength, elongation, flexibility, and dissolution rate in the oral cavity.

In Example 1 according to the present invention, surprising results were shown in strength, elongation, flexibility, and dissolution rate in the oral cavity of film without adding excipients to improve its physical properties. Eventually, the degree of improvement in physical properties depending on various component ratios regarding composition for edible film, which consists of hyroxypropyl methylcellulose and polyvinyl alcohol-polyethylene glycol copolymer (PVA-PEG Copolymer) selected in example 1, was examined

<Examples 2 to 7> manufacture of edible film by component ratio of this invention

30g of composition for edible film, which consists of HPMC and PVA-PEG Copolymer with component ratio, specified in the following table 4, into suitable volume of purified water, they are mixed therein. Then, edible film is manufactured by using the same method as above, and it is presented in example 2 to 7.

<Experimental Example 2> measuring physical properties of edible film and dissolution rate in the oral cavity

Tensile strength (film strength and elongation), flexibility, and dissolution rate in the oral cavity were measured and presented in Table 4 in Examples 2 to 7 by using the same method as experimental example 2 according to the present invention.

Table 4

As known in the table presented as above, composition of HPMC and PVA-PEG copolymer has significantly high performance in physical properties of film throughout overall range of weight ratio 95:5~5:95, and it is verified that the dissolving time is less than 15 seconds by measured dissolution rate in the oral cavity

Therefore, composition for film according to the present invention enables us to manufacture intended pharmaceutical preparation for edible film regardless of using excipients to improve physical properties of film. It is anticipated that pharmaceutical preparation can be manufactured without limiting contents of drug due to excipients

Above all, in order to know whether composition for film by this invention enables us to manufacture intended pharmaceutical preparation for edible film without limiting types and contents of drug, pharmaceutical preparation for edible film is manufactured for various drugs which have molecular weight of 100 to 600(g/mol), and physical properties of film (strength, elongation, and flexibility) and dissolution rate in the oral cavity were evaluated.

<Preparation Example 1> pharmaceutical preparation for edible film containing drugs which have molecular weight of 100 to 200

1.1 pharmaceutical preparation for edible film containing acetaminophene

(1) 15.17 weight % (w/w) of acetaminophene is dissolved thoroughly in suitable volume of purified water;

(2) 64.82 weight % (w/w) of the composition for edible film consisting of hyroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG Copolymer) manufactured in Example 1 is added into the above solution. It is stirred until being dissolved thoroughly;

(3) Suitable volume of L-menthol and strawberry flavor is added into the above (2) solution in order to flavor with dosage form of film. After that, it is stirred until being dissolved homogeneously.

(4) After it is left for 24 hours at room temperature in order to remove bubbles of manufactured solution, it is casted in stainless steel molder by film coating machine. After allowing this solution to dry out at 80^oC, the film is peeled off. Homogenous pharmaceutical preparation for edible film, which has width of 200 ㎛ and size of 25 mm * 30 mm, is manufactured.

1-2 pharmaceutical preparation for edible film containing l-menthol

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 19.07 weight %(w/w) of major component l-menthol and 60.73 weight%(w/w) of composition for edible film manufactured in example 1.

1-3 pharmaceutical preparation for edible film containing nicotine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 20.21 weight % (w/w) of major component nicotine and 59.85 weight%(w/w) of composition for edible film manufactured in example 1.

1-4 pharmaceutical preparation for edible film containing benzocaine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 17.11 weight % (w/w) of major component benzocaine and 65.51 weight%(w/w) of composition for edible film manufactured example 1.

1-5 pharmaceutical preparation for edible film containing ascorbic acid

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 25.33 weight %(w/w) of major component ascorbic acid and 50.55 weight%(w/w) of composition for edible film manufactured in example 1.

1-6 pharmaceutical preparation for edible film containing phentermine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 16.22 weight % (w/w) of major component phentermine HCl and 64.11 weight%(w/w) of composition for edible film manufactured in example 1.

1-7 pharmaceutical preparation for edible film containing caffeine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 10.42 weight % (w/w) of major component caffeine and 66.25 weight%(w/w) of composition for edible film manufactured in example 1.

<Preparation Example 2> pharmaceutical preparation for edible film containing drugs which have molecular weights of 200 to 300

2-1 pharmaceutical preparation for edible film containing phenylephrine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 9.35 weight % (w/w) major component phenylephrine HCl and 70.33 weight%(w/w) of composition for edible film manufactured in example 1.

2-2 pharmaceutical preparation for edible film containing pseudoephedrine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 16.45 weight % (w/w) of major component pseudoephedrine HCl and 73.77 weight%(w/w) of composition for edible film manufactured in example 1.

2-3 pharmaceutical preparation for edible film containing baclofen

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 10.44 weight % (w/w) of major component baclofen and 69.11 weight%(w/w) of composition for edible film manufactured in example 1.

2-4 pharmaceutical preparation for edible film of memantine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 20.70 weight % (w/w) major component memantine HCl and 58.73 weight%(w/w) of composition for edible film manufactured in example 1.

2-5 pharmaceutical preparation for edible film containing selegiline HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 10.92 weight % (w/w) of major component selegiline HCl and 71.66 weight%(w/w) of composition for edible film manufactured in example 1.

2-6 pharmaceutical preparation for edible film containing nitroglycerin

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 15.11 weight % (w/w) of major component nitroglycerin and 66.41 weight%(w/w) of composition for edible film manufactured in example 1.

2-7 pharmaceutical preparation for edible film of simethicone

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 21.00 weight % (w/w) of major component simethicone and 57.94 weight%(w/w) of composition for edible film manufactured in example 1.

2-8 pharmaceutical preparation for edible film containing diethylpropion HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 5.99 weight % (w/w) of major component diethylpropion HCl and 73.67 weight%(w/w) of composition for edible film manufactured in example 1.

2-9 pharmaceutical preparation for edible film containing cimetidine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 15.87 weight % (w/w) of major component cimetidine and 65.00 weight%(w/w) of composition for edible film manufactured in example 1.

2-10 pharmaceutical preparation for edible film containing ketoprofen

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 10.22 weight % (w/w) of major component ketoprofen and 70.91 weight%(w/w) of composition for edible film manufactured in example 1.

2-11 pharmaceutical preparation for edible film containing lamotrigine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 15.99 weight % (w/w) of major component lamotrigine and 63.85 weight%(w/w) of composition for edible film manufactured in example 1.

2-12 pharmaceutical preparation for edible film containing pemirolast potassium

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 11.74 weight % (w/w) of major component pemirolast potassium and 69.33 weight%(w/w) of composition for edible film manufactured in example 1.

2-13 pharmaceutical preparation for edible film containing voglibose

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 20.22 weight % (w/w) of major component voglibose and 58.66 weight%(w/w) of composition for edible film manufactured in example 1.

2-14 pharmaceutical preparation for edible film containing rizatriptan

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 5.77 weight % (w/w) of major component rizatriptan and 76.01 weight%(w/w) of composition for edible film manufactured in example 1.

2-15 pharmaceutical preparation for edible film containing chloropheniramine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 12.66 weight % (w/w) of major component chloropheniramine and 69.11 weight%(w/w) of composition for edible film manufactured in example 1.

2-16 pharmaceutical preparation for edible film containing mazindol

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 18.25 weight % (w/w) of major component mazindol and 60.88 weight%(w/w) of composition for edible film manufactured in example 1.

2-17 pharmaceutical preparation for edible film containing zolmitriptan

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 8.22 weight % (w/w) of major component zolmitriptan and 71.48 weight%(w/w) of composition for edible film manufactured in example 1.

2-18 pharmaceutical preparation for edible film containing tizanidine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 19.88 weight % (w/w) of major component tizanidine HCl and 57.12 weight%(w/w) of composition for edible film manufactured in example 1.

2-19 pharmaceutical preparation for edible film containing diphenhydramine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 5.31 weight % (w/w) of major component diphenhydramine HCl and 78.77 weight%(w/w) of composition for edible film manufactured in example 1.

2-20 pharmaceutical preparation for edible film containing sumatriptan

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 17.55 weight % (w/w) of major component sumatriptan and 68.70 weight%(w/w) of composition for edible film manufactured in example 1.

2-21 pharmaceutical preparation for edible film containing diclofenac

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 1-1 by using 10.30 weight % (w/w) of major component diclofenac and 71.22 weight%(w/w) of composition for edible film manufactured in example 1.

<Preparation Example 3> pharmaceutical preparation for edible film containing drugs which have molecular weights of 300 to 400

3-1 pharmaceutical preparation for edible film containing Ramosetron HCl

(1) 0.22 weight (w/w) of Ramosetron HCl is dissolved thoroghtly in suitable volume of purified water

(2) 79.11 weight%(w/w) of the composition for edible film consisting of hyroxypropyl methylcellulose (HPMC) and Polyvinyl alcohol-polyethylene glycol Copolymer manufactured in example 1 is added into the above solution. It is stirred until being dissolved thoroughly

(3) Suitable volume of citric acid, L-menthol, or strawberry flavor is added into the above (2) solution in order to flavor dosage form of film. Then, it is stirred sufficiently until it is dissolved homogeneously

(4) It is left at room temperature for 24 hours in order to remove bubbles of manufactured solution. It is casted in stainless steel molder by using film coating machine. After allowing this solution to dry out at 80^oC, the film is peeled off, homogenous pharmaceutical preparation for edible film with width of 200 ㎛ and size of 25 mm * 30 mm is manufactured.

3-2 pharmaceutical preparation for edible film containing alprazolam

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 5.25 weight % (w/w) of major component alprazolam and 72.33 weight%(w/w) of composition for edible film manufactured in example 1.

3-3 pharmaceutical preparation for edible film containing desloratadine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 10.88 weight % (w/w) of major component desloratadine and 70.00 weight%(w/w) of composition for edible film manufactured in example 1.

3-4 pharmaceutical preparation for edible film containing olanzapine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 22.74 weight % (w/w) of major component olanzapine and 55.69 weight % (w/w) of composition for edible film manufactured in example 1.

3-5 pharmaceutical preparation for edible film containing levonorgestrel

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 25.50 weight % (w/w) of major component levonorgestrel and 54.11 weight%(w/w) of composition for edible film manufactured in example 1.

3-6 pharmaceutical preparation for edible film containing ondansetron HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 15.66 weight % (w/w) of major component ondansetron HCl and 74.00 weight%(w/w) of composition for edible film manufactured in example 1.

3-7 pharmaceutical preparation for edible film containing metoclopramide HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 13.24 weight % (w/w) of major component metoclopramide HCl and 77.18 weight%(w/w) of composition for edible film manufactured in example 1.

3-8 pharmaceutical preparation for edible film containing fentanyl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 23.05 weight % (w/w) major component fentanyl and 58.04 weight%(w/w) of composition for edible film manufactured in example 1.

3-9 pharmaceutical preparation for edible film containing famotidine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 8.08 weight % (w/w) of major component famotidine and 72.07 weight%(w/w) of composition for edible film manufactured in example 1.

3-10 pharmaceutical preparation for edible film containing topiramate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 16.82 weight % (w/w) of major component topiramate and 65.44 weight%(w/w) of composition for edible film manufactured in example 1.

3-11 pharmaceutical preparation for edible film containing cetylpyridinium Cl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 10.61 weight % (w/w) of major component cetylpyridinium Cl and 70.57 weight%(w/w) of composition for edible film manufactured in example 1.

3-12 pharmaceutical preparation for edible film containing phendimetrazine tartrate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 3.84 weight % (w/w) of major component phendimetrazine tartrate and 70.99 weight%(w/w) of composition for edible film manufactured in example 1.

3-13 pharmaceutical preparation for edible film containing triazolam

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 19.12 weight % (w/w) of major component triazolam and 60.54 weight%(w/w) of composition for edible film manufactured in example 1.

3-14 pharmaceutical preparation for edible film containing zolpidem

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 20.21 weight % (w/w) of major component zolpidem and 58.93 weight%(w/w) of composition for edible film manufactured in example 1.

3-15 pharmaceutical preparation for edible film containing omeprazole

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 9.74 weight % (w/w) of major component omeprazole and 70.50 weight%(w/w) of composition for edible film manufactured in example 1.

3-16 pharmaceutical preparation for edible film containing torasemide

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 17.39 weight % (w/w) of major component torasemide and 64.00 weight%(w/w) of composition for edible film manufactured in example 1.

3-17 pharmaceutical preparation for edible film containing granisetron HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 13.12 weight % (w/w) of major component granisetron HCl and 69.42 weight%(w/w) of composition for edible film manufactured in example 1.

3-18 pharmaceutical preparation for edible film containing ranitidine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 18.75 weight % (w/w) of major component ranitidine HCl and 62.00 weight%(w/w) of composition for edible film manufactured in example 1.

3-19 pharmaceutical preparation for edible film containing meloxicam

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 20.20 weight % (w/w) of major component meloxicam and 60.00 weight%(w/w) of composition for edible film manufactured in example 1.

3-20 pharmaceutical preparation for edible film containing lansoprazole

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 11.25 weight % (w/w) of major component lansoprazole and 68.99 weight%(w/w) of composition for edible film manufactured in example 1.

3-21 pharmaceutical preparation for edible film containing dextromethorphan HBr

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 6.42 weight % (w/w) of major component dextromethorphan HBr and 72.21 weight%(w/w) of composition for edible film manufactured in example 1.

3-22 pharmaceutical preparation for edible film containing olopatadine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 11.33 weight % (w/w) of major component olopatadine HCl and 67.85 weight%(w/w) of composition for edible film manufactured in example 1.

3-23 pharmaceutical preparation for edible film containing loratadine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 12.54 weight % (w/w) of major component loratadine and 69.10 weight%(w/w) of composition for edible film manufactured in example 1.

3-24 pharmaceutical preparation for edible film containing doxylamine succinate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 8.35 weight % (w/w) of major component doxylamine succcinate and 71.68 weight%(w/w) of composition for edible film manufactured in example 1.

3-25 pharmaceutical preparation for edible film containing tadalafil

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 25.64 weight % (w/w) of major component tadalafil and 54.91 weight%(w/w) of composition for edible film manufactured in example 1.

3-26 pharmaceutical preparation for edible film containing meclizine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using meclizine 14.45 weight % (w/w) of major component and 77.02 weight%(w/w) of composition for edible film manufactured in example 1.

3-27 pharmaceutical preparation for edible film containing dexamethasone

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 17.37 weight %(w/w) of major component dexamethasone and 65.31 weight%(w/w) of composition for edible film manufactured in example 1.

3-28 pharmaceutical preparation for edible film containing oxybutynin HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 3-1 by using 20.00 weight %(w/w) of major component oxybutynin HCl and 60.10 weight %(w/w) of composition for edible film manufactured in example 1.

<Preparation Example 4> pharmaceutical preparation for edible film containing drugs which have molecular weights of 400 to 500

4.1 Pharmaceutical preparation for edible film of Cetirizine HCl

(1) 22.22 weight %(w/w) of Cetirizine HCl is dissolved in suitable volume of purified.

(2) 53.77 weight %(w/w) of composition for edible film consisting of Hydroxypropyl methylcellulose and polyvinyl alcohol-polyethylene glycol Co-polymer manufactured in example 1 is added into the above solution. It is stirred until being dissolved thoroughly.

(3) Suitable volume of L-methol and lemon flavor are added into the above (2) solution in order to flavor the dosage form of film. Then, it is stirred until it is dissolved homogeneously.

(4) After it is left for 24 hours at room temperature in order to remove bubbles of manufactured solution, it is casted in stainless steel molder by using film coating machine. After allowing it to dry out at 80^oC, the film is peeled off. Homogenous pharmaceutical preparation for edible film which has width of 200 ㎛ and size of 25 mm * 30 mm is manufactured.

4-2 pharmaceutical preparation for edible film containing citalopram HBr

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 11.11 weight % (w/w) of major component citalopram HBr and 68.66 weight%(w/w) of composition for edible film manufactured in example 1.

4-3 pharmaceutical preparation for edible film containing tarafenacin

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 8.56 weight % (w/w) of major component tarafenacin and 70.99 weight%(w/w) of composition for edible film manufactured in example 1.

4-4 pharmaceutical preparation for edible film containing tamsulosine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 15.42 weight % (w/w) of major component tamsulosine and 66.12 weight%(w/w) of composition for edible film manufactured in example 1.

4-5 pharmaceutical preparation for edible film containing risperidone

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 13.47 weight % (w/w) of major component risperidone and 65.80 weight%(w/w) of composition for edible film manufactured in example 1.

4-6 pharmaceutical preparation for edible film containing escitalopram oxalate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 17.48 weight % (w/w) of major component escitalopram oxalate and 58.11 weight%(w/w) of composition for edible film manufactured in example 1.

4-7 pharmaceutical preparation for edible film containing ambroxol HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 8.08 weight % (w/w) of major component ambroxol HCl and 70.10 weight%(w/w) of composition for edible film manufactured in example 1.

4-8 pharmaceutical preparation for edible film containing donepezil HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 12.34 weight % (w/w) of major component donepezil HCl and 69.91 weight%(w/w) of composition for edible film manufactured in example 1.

4-9 pharmaceutical preparation for edible film containing ramipril

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 14.05 weight %(w/w) of major component ramipril and 61.45 weight%(w/w) of composition for edible film manufactured in example 1.

4-10 pharmaceutical preparation for edible film containing sildenafil

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 20.85 weight % (w/w) of major component sildenafil and 58.90 weight%(w/w) of composition for edible film manufactured in example 1.

4-11 pharmaceutical preparation for edible film containing aripirazole

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 17.10 weight % (w/w) of major component aripirazole and 60.55 weight%(w/w) of composition for edible film manufactured in example 1.

4-12 pharmaceutical preparation for edible film containing tianeptine Na

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 7.96 weight % (w/w)major component tianeptine Na and 74.50 weight%(w/w) of composition for edible film manufactured in example 1.

4-13 pharmaceutical preparation for edible film containing levocetirizine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 14.92 weight % (w/w) of major component levocetirizine HCl and 68.24 weight%(w/w) of composition for edible film manufactured in example 1.

4-14 pharmaceutical preparation for edible film containing buprenorphine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 2.62 weight % (w/w) of major component buprenorphine and 80.00 weight%(w/w) of composition for edible film manufactured in example 1.

4-15 pharmaceutical preparation for edible film containing ebastine

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 8.58 weight % (w/w) of major component ebastine and 70.72 weight%(w/w) of composition for edible film manufactured in example 1.

4-16 pharmaceutical preparation for edible film containing solifenacin succinate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 10.88 weight % (w/w) of major component solifenacin succinate and 65.30 weight%(w/w) of composition for edible film manufactured in example 1.

4-17 pharmaceutical preparation for edible film containing nicergoline

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 16.27 weight % (w/w) of major component nicergoline and 61.76 weight%(w/w) of composition for edible film manufactured in example 1.

4-18 pharmaceutical preparation for edible film containing glimepiride

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 18.62 weight % (w/w) of major component glimepiride and 63.51 weight%(w/w) composition for edible film manufactured in example 1.

4-19 pharmaceutical preparation for edible film containing mosapride

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 4-1 by using 14.81 weight % (w/w) of major component mosapride and 65.66 weight%(w/w) of composition for edible film manufactured in example 1.

<Preparation Example 5> pharmaceutical preparation for edible film containing drugs which have molecular weight of 500 to 600

5-1 pharmaceutical preparation for edible film containing Loperamide HCl

(1) 72.66 weight %(w/w) of compostion for edible film consisting of hyroxypropyl methylcellulose(HPMC) and Polyvinyl alcohol-polyethylene glycol Copolymer manufactured in example 1 is added into suitable volume of purified water . It is stirred until being dissolved thoroughly

(2) 2.22 weight %(w/w) of Loperamide HCl is added into the solution presented as above, and is mixed with this solution sufficiently

(3) Suitable volume of L-methol and pineapple flavor are added into (2) solution presented as above in order to flavor the dosage form of film. Then, it is stirred until it is dissolved homogeneously.

(4) After it is left for 24 hours at room temperature in order to remove manufactured solution, it is casted in stainless steel molder by using film coating machine. After allowing this solution to dry out at 80^oC, the film is peeled off. Homogenous pharmaceutical preparation for edible film, which has width 200 ㎛ and size of 25 mm * 30 mm, is manufactured.

5-2 pharmaceutical preparation for edible film containing udenafil

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 22.33 weight % (w/w) of major component udenafil and 50.28 weight%(w/w) of composition for edible film manufactured in example 1.

5-3 pharmaceutical preparation for edible film containing fesoterodine fumarate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 9.00 weight % (w/w) of major component fesoterodine fumarate and 72.61 weight%(w/w) of composition for edible film manufactured in example 1.

5-4 pharmaceutical preparation for edible film containing mirodenafil

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 20.57 weight % (w/w) of major component mirodenafil and 57.40 weight%(w/w) of composition for edible film manufactured in example 1.

5-5 pharmaceutical preparation for edible film containing fexofenadine HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 16.10 weight % (w/w) of major component fexofenadine HCl and 61.99 weight%(w/w) of composition for edible film manufactured in example 1.

5-6 pharmaceutical preparation for edible film containing doxazosin mesylate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 11.81 weight % (w/w) of major component doxazosin mesylate and 70.88 weight%(w/w) of composition for edible film manufactured in example 1.

5-7 pharmaceutical preparation for edible film containing olmesartan medoxomil

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 19.16 weight % (w/w) of major component olmesartan medoxomil and 60.76 weight%(w/w) of composition for edible film manufactured in example 1.

5-8 pharmaceutical preparation for edible film containing vardenafil 2HCl

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 21.64 weight % (w/w) of major component vardenafil 2HCl and 57.99 weight%(w/w) of composition for edible film manufactured in example 1.

5-9 pharmaceutical preparation for edible film containing amlodipine besylate

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 8.69 weight % (w/w) of major component amlodipine besylate and 73.00 weight%(w/w) of composition for edible film manufactured in example 1.

5-10 pharmaceutical preparation for edible film containing Montelukast Na

Pharmaceutical preparation for edible film is manufactured in the same method as preparation example 5-1 by using 5.04 weight % (w/w) of major component Montelukast Na and 70.34 weight%(w/w) of composition for edible film manufactured in example 1.

<Experimental Example 3> measuring physical properties and dissolution rate in the oral cavity of pharmaceutical preparation for edible film according to this invention.

Tensile strength(strength of film and elongation), flexibility, and dissolution rate in the oral cavity regarding pharmaceutical preparation for edible film containing drugs in preparation examples by using the same method as experimental example 1 described as above according to this invention, were measured and presented in Table 5.

Table 5

As it is known in Table 5 presented as above, pharmaceutical preparation for edible film containing drugs which have molecular weight of 100 or 600 (g/mol) by using composition for edible film consisting of hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol Copolymer(PVA-PEG Copolymer) according to this invention, enables us to manufacture the intended dosage form of edible film regardless of adding excipients. Also, it has high performing effect on all physical properties including strength, elongation, flexibility, and dissolution rate in the oral cavity of film without limitation on types and contents of drugs.

Claims (12)

1. A composition for edible film consisting of hyroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol copolymer (PVA-PEG copolymer)
2. The composition for edible film according to claim 1, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed with in the weight(w/w%) ratio of 95:5~5:95
3. The composition for edible film according to claim 2, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed in the weight(w/w%) ratio of 95:5~30:70
4. The composition for edible film according to claim 3, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed in the weight(w/w%) ratio of 50:50
5. The composition for edible film consisting of hyroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol copolymer (PVA-PEG copolymer) and a pharmaceutical preparation for edible film containing drugs
6. A pharmaceutical preparation for edible film according to claim 5, wherein its drug has molecular weight of 100 to 600 (g/mol)
7. The pharmaceutical preparation for edible film according to claim 6, wherein its drug is selected from the group consisting of acetaminophene, l-menthol, nicotine, benzocaine, ascorbic acid, phentermine HCl, caffeine, phenylephrine HCl, pseudoephedrine HCl, baclofen, memantine HCl, selegiline HCl, nitroglycerin, simethicone, diethylpropion HCl, cimetidine, ketoprofen, lamotrigine, pemirolast potassium, voglibose, rizatriptan, chloropheniramine, mazindol, zolmitriptan, tizanidine HCl, diphenhydramine HCl, sumatriptan, diclofenac, Ramosetron Hcl, alprazolam, deloratadine, olanzapine, levonorgestrel, ondansetron HCl, metoclopramide HCl, fentanyl, famotidine, topiramate, cetylpyridinium Cl, phendimetrazine tartrate, triazolam, zopidem, omeprazole, torasemide, granisetron HCl, ranitidine HCl, meloxicam, lansoprazole, dextromethorphan HBr, olopatadine HCl, loratadine, doxylamine succinate, tadalafil, meclizine, dexamethasone, oxybutynin HCl, Cetirizine HCl, citalopram HBr, tarafenacin, tamsulosine, risperidone, escitalopram oxalate, ambroxol HCl, donepezil HCl, ramipril, sildenafil, aripirazole, tianeptine Na, levocetirizine HCl, buprenorphine, ebastine, solifenacin succinate, nicergoline, glimepride, mosapride, Loperamide HCl, udenafil, fesoterodine fumarate, mirodenafil, fexofenadine HCl, doxazosin mesylate, olmesartan medoxomil, vardenafil 2HCl, amlodipine besylate or Montelukast Na
8. The pharmaceutical preparation for edible film according to claim 5, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed in the weight(w/w%) ratio of 95:5~ 5:95
9. The pharmaceutical preparation for edible film according to claim 8, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed in the weight(w/w%) ratio of 95:5~ 30:70
10. The pharmaceutical preparation for edible film according to claim 9, wherein hyroxypropyl methylcellulose(HPMC) and polyvinyl alcohol-polyethylene glycol copolymer(PVA-PEG copolymer) are mixed in the weight(w/w%) ratio of 50:50
11. The pharmaceutical preparation for edible film according to claim 5, wherein flavor improvement agents are added
12. The pharmaceutical preparation for edible film according to claim 11, wherein one, two or three types of flavor improvement agents are selected from the group consisting of L-menthol, strawberry flavor, lemon flavor, pineapple flavor, acesulfame potassium, aspartame, sucralose or citric acid