INTRAORAL FAST-DISINTEGRATING FORMULATION CONTAINING HEMP OIL EXTRACT OR HEMP POWDER EXTRACT AS RAW MATERIAL OF FORMULATION

Abstract

The present disclosure provides an intraoral fast disintegrating formulation containing hemp oil extract or hemp powder extract as a raw material of the formulation, wherein the formulation contains a water-soluble binder, an inorganic material and a surfactant.

Claims

1. An intraoral fast disintegrating formulation comprising hemp oil extract or hemp powder extract as an active ingredient of the formulation, wherein the formulation is an intraoral fast disintegrating formulation comprising a water-soluble polymer, an inorganic material and a surfactant.

2. The intraoral fast disintegrating formulation according to claim 1, wherein the content of cannabidiol (CBD) in the hemp oil extract is 80% or higher.

3. The intraoral fast disintegrating formulation according to claim 1, wherein the hemp powder extract comprises cannabidiol (CBD) but is substantially free from one or more selected from a group consisting of tetrahydrocannabidiol (THC), cannabigerol (CBG), cannabichromene (CBC) and cannabinol (CBN).

4. The intraoral fast disintegrating formulation according to claim 1, wherein the water-soluble polymer is hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) or a mixture thereof.

5. The intraoral fast disintegrating formulation according to claim 4, wherein the water-soluble polymer is a mixture of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC).

6. The intraoral fast disintegrating formulation according to claim 1, 4 or 5, wherein the water-soluble polymer is a mixture of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) at a weight ratio (HPC:HPMC) of 1:1.3-2.5.

7. The intraoral fast disintegrating formulation according to claim 1, wherein the inorganic material is one or more selected from a group consisting of calcium phosphate, calcium sulfate, calcium stearate, calcium carbonate, talc, zinc stearate, titanium dioxide and silicon dioxide.

8. The intraoral fast disintegrating formulation according to claim 7, wherein the inorganic material is one or more selected from a group consisting of calcium phosphate, talc, silicon dioxide and titanium dioxide.

9. The intraoral fast disintegrating formulation according to claim 1, wherein the surfactant is Tween 80.

10. The intraoral fast disintegrating formulation according to claim 1 or 9, wherein the surfactant is comprised at a content of 1-15 wt % based on the total weight of the formulation.

11. The intraoral fast disintegrating formulation according to any of claims 1 to 10, wherein the formulation further comprises a thickener.

12. The intraoral fast disintegrating formulation according to claim 11, wherein the thickener is one or more selected from a group consisting of xanthan gum, guar gum and gum arabic.

13. The intraoral fast disintegrating formulation according to any of claims 1 to 12, wherein the formulation further comprises a flavoring agent or a sweetener, or further comprises both a flavoring agent and a sweetener.

14. The intraoral fast disintegrating formulation according to any of claims 1 to 13, wherein the hemp oil extract is comprised at a content of 30-40 wt % based on the total weight of the formulation.

15. The intraoral fast disintegrating formulation according to any of claims 1 to 13, wherein the hemp powder extract is comprised at a content of 25-35 wt % based on the total weight of the formulation.

16. The intraoral fast disintegrating formulation according to any of claims 1 to 15, wherein the inorganic material is comprised at a content of 0.5-3 wt % based on the total weight of the formulation.

17. The intraoral fast disintegrating formulation according to any of claims 1 to 16, wherein, when the formulation comprises hemp oil extract, the hemp oil extract, the water-soluble polymer and the inorganic material are mixed at a weight ratio (hemp oil extract:water-soluble polymer:inorganic material, which is a water-insoluble excipient) of 7-12:8-12:0.1-3.

18. The intraoral fast disintegrating formulation according to any of claims 1 to 17, wherein, when the formulation comprises hemp powder extract, the hemp powder extract, the water-soluble polymer and the inorganic material are mixed at a weight ratio (hemp powder extract:water-soluble polymer:inorganic material) of 3-10:6-15:0.05-1.

19. The intraoral fast disintegrating formulation according to any of claims 1 to 18, wherein the formulation is an intraoral fast disintegrating film.

Description

DETAILED DESCRIPTION

[0023] Hereinafter, the present disclosure is described in detail through examples. However, the examples of the present disclosure may be changed into various other forms and should not be understood to limit the scope of the present disclosure. The examples of the present disclosure are provided so that the present disclosure can be more fully understood by those having ordinary knowledge in the art.

Experimental Example 1

Preparation of Film Formulation Containing Hemp Oil Extract

[0024] A film formulation containing hemp oil extract was prepared as follows. 0.0% THC phytocannabinoid-rich hemp oil (87.06% CBD, 0.0% THC), which is hemp oil extract available from ORGANIC lisiherb, was added to ethanol and then dissolved by stirring. Then, after adding purified water, a surfactant, a flavoring agent, a sweetener, a thickener and other excipients, the mixture was homogenized using a homogenizer (Ultra Turrax T-25, IKA). Then, after adding a water-soluble polymer and an inorganic material, the mixture was homogenized using the same homogenizer. Then, after removing gas from the film solution at 30° C. in vacuo, followed by cooling to room temperature, the solution was coated on a polyethylene terephthalate (PET) film to an appropriate thickness. Then, a film formulation containing hemp oil extract was prepared by drying at 60° C. The effect of the addition amount of the inorganic material on the disintegration of the film is shown in Tables 1-4.

TABLE-US-00001 TABLE 1 Comp. Comp. Comp. Comp. Additives Ex. 1-1 Ex. 1-2 Ex. 1-1 Ex. 1-2 Ex. 1-3 Ex. 1-3 Ex. 1-4 Hemp oil extract 9.03 9.03 9.03 9.03 9.03 9.03 9.03 Tween 80 1.98 1.98 1.98 1.98 1.98 1.98 1.98 Peppermint oil 0.94 0.94 0.94 0.94 0.94 0.94 0.94 Sweetener Adequate Adequate Adequate Adequate Adequate Adequate Adequate TiO.sub.2 0.00  0.072 0.24 0.36 0.48 0.72 6.00 HPMC & HPC 10.06  10.06  10.06  10.06  10.06  10.06  10.06  Purified water & To 100% ethanol Water-soluble — 139.72:1 41.92:1 27.94:1 20.96:1 13.97:1 1.68:1 polymer (HPMC & HPC):inorganic material (TiO.sub.2) Disintegration 3 minutes About 3 Within 50 Within 20 Wthin 40 About 1 About 1 and 30 minutes seconds seconds seconds minute minute seconds or longer Foreign body 5   5   5   5   5   3   1   sensation in mouth Flexibility Not Not Not Not Not Not Broken broken broken broken broken broken broken

TABLE-US-00002 TABLE 2 Comp. Comp. Comp. Comp. Additives Ex. 2-1 Ex. 2-2 Ex. 2-1 Ex. 2-2 Ex. 2-3 Ex. 2-3 Ex. 2-4 Hemp oil extract 9.03 9.03 9.03 9.03 9.03 9.03 9.03 Tween 80 1.98 1.98 1.98 1.98 1.98 1.98 1.98 Peppermint oil 0.94 0.94 0.94 0.94 0.94 0.94 0.94 Sweetener Adequate Adequate Adequate Adequate Adequate Adequate Adequate Silicon dioxide 0.00  0.072 0.24 0.36 0.48 0.72 6.00 HPMC & HPC 10.06  10.06  10.06  10.06  10.06  10.06  10.06  Purified water & To 100% ethanol Water-soluble — 139.72:1 41.92:1 27.94:1 20.96:1 13.97:1 1.68:1 polymer (HPMC & PC):inorganic material (silicon dioxide) Disintegration 4 minutes About 3 Within 50 Wthin 30 Within 50 About 1 About 1 or longer minutes seconds seconds seconds minute minute Foreign body 5   5   5   5   5   3   1   sensation in mouth Flexibility Not Not Not Not Not Not Broken broken broken broken broken broken broken

TABLE-US-00003 TABLE 3 Comp. Comp. Comp. Comp. Additives Ex. 3-1 Ex. 3-2 Ex. 3-1 Ex. 3-2 Ex. 3-3 Ex. 3-3 Ex. 3-4 Hemp oil extract 9.03 9.03 9.03 9.03 9.03 9.03 9.03 Tween 80 1.98 1.98 1.98 1.98 1.98 1.98 1.98 Peppermint oil 0.94 0.94 0.94 0.94 0.94 0.94 0.94 Sweetener Adequate Adequate Adequate Adequate Adequate Adequate Adequate Talc 0.00  0.072 0.24 0.36 0.48 0.72 6.00 HPMC & HPC 10.06  10.06  10.06  10.06  10.06  10.06  10.06  Purified water & To 100% ethanol Water-soluble — 139.72:1 41.92:1 27.94:1 20.96:1 13.97:1 1.68:1 polymer (HPMC & HPC):inorganic material (talc) Disintegration 3 minutes About 3 Within 50 Within 20 Within 50 About 1 About 1 and 30 minutes seconds seconds seconds minute minute seconds or longer Foreign body 5   5   5   5   5   3   1   sensation in mouth Flexibility Not Not Not Not Not Not Broken broken broken broken broken broken broken

TABLE-US-00004 TABLE 4 Comp. Comp. Comp. Comp. Additives Ex. 4-1 Ex. 4-2 Ex. 4-1 Ex. 4-2 Ex. 4-3 Ex. 4-3 Ex. 4-4 Cannabidiol oil 9.03 9.03 9.03 9.03 9.03 9.03 9.03 Tween 80 1.98 1.98 1.98 1.98 1.98 1.98 1.98 Peppermint oil 0.94 0.94 0.94 0.94 0.94 0.94 0.94 Sweetener Adequate Adequate Adequate Adequate Adequate Adequate Adequate Calcium phosphate 0.00  0.072 0.24 0.36 0.48 0.72 6.00 HPMC & HPC 10.06  10.06  10.06  10.06  10.06  10.06  10.06  Purified water & To 100% ethanol Water-soluble — 139.72:1 41.92:1 27.94:1 20.96:1 13.97:1 1.68:1 polymer (HPMC & HPC):inorganic material (calcium phosphate) Disintegration 4 minutes About 3 Within 40 Within 20 Within 40 About 1 About 1 or longer minutes seconds seconds seconds minute minute Foreign body 5   5   5   5   5   3   1   sensation in mouth Flexibility Not Not Not Not Not Not Broken broken broken broken broken broken broken

{circle around (1)} Intraoral Disintegration Test

[0025] The intraoral disintegration rate of the prepared film was tested as follows. The films prepared in Tables 1-4 were cult to a size of 37×27 mm and placed in the mouth of 10 adults. Then, the average time spent until the film was disintegrated by saliva was measured (Criterion of evaluation: The film should not be observed in the mouth, and 80% of the entire film should be dissolved, dispersed or disintegrated. The film weight should be 20% or less of the initial weight.).

{circle around (2)} Intraoral Foreign Body Sensation Test

[0026] Foreign body sensation in the mouth was tested after the disintegration of the film was completed. It was investigated whether foreign body sensation remains in the mouth after the intraoral disintegration test.

TABLE-US-00005 TABLE 5 Eval- Score uation Standard 1 Poor Very severe foreign body sensation and unpleasant taste remain in the mouth after disintegration of the film. 2 Not Severe foreign body sensation and unpleasant taste good remain in the mouth after disintegration of the film. 3 Not bad Slight foreign body sensation and unpleasant taste remain in the mouth after disintegration of the film. 4 Good No foreign body sensation but slight unpleasant taste remains in the mouth after disintegration of the film. 5 Excel- No foreign body sensation or unpleasant taste remains lent in the mouth after disintegration of the film.

{circle around (3)} Flexibility Test

[0027] The flexibility of the film was tested. It was investigated whether breakage occurs when the films as described in Tables 1-4 were folded in half (Criterion of evaluation: not broken or broken. Even a slight breakage was evaluated as broken.).

{circle around (4)} Test Result

[0028] The results of testing the intraoral disintegration, foreign body sensation in the mouth and flexibility of the films as described in Tables 1-4 are shown in Table 1-4.

Experimental Example 2

Preparation of Film Formulation Containing Hemp Powder Extract

[0029] A film formulation containing hemp powder extract was prepared as follows. RGANIC lisiherb's CBD powder was added to ethanol and then dissolved by stirring. Then, after adding purified water, a surfactant, a flavoring agent, a sweetener, a thickener and other excipients, the mixture was homogenized using a homogenizer (Ultra Turrax T-25, IKA). Then, after adding a water-soluble polymer and an inorganic material, the mixture was homogenized using the same homogenizer. Then, after removing gas from the film solution at 30° C. in vacuo, followed by cooling to room temperature, the solution was coated on a polyethylene terephthalate (PET) film to an appropriate thickness. Then, a film formulation containing hemp powder extract was prepared by drying at 60° C. The effect of the addition amount of the inorganic material on the disintegration of the film is shown in Tables 6-9.

TABLE-US-00006 TABLE 6 Comp. Comp. Example Example Comp. Additives Ex. 5-1 Ex. 5-2 5-1 5-2 Ex. 5-3 Hemp powder extract 6.34 6.34 6.34 6.34 6.34 Tween 80 1.60 1.60 1.60 1.60 1.60 Peppermint oil 1.01 1.01 1.01 1.01 1.01 Sweetener Adequate Adequate Adequate Adequate Adequate TiO.sub.2 0.00  0.075  0.375 0.5  6.25 HPMC & HPC 12.67  12.67  12.67  12.67  12.67  Purified water & ethanol To 100% Water-soluble polymer (HPMC & — 168.93:1 33.79:1 25.34:1 2.03:1 HPC):inorganic material (TiO.sub.2) Disintegration 4 minutes About 3 Within 40 Within 20 About 1 or longer minutes seconds seconds minute Foreign body sensation in mouth 4   4   5   5   1   Flexibility Not Not Not Not Broken broken broken broken broken

TABLE-US-00007 TABLE 7 Comp. Comp. Example Example Comp. Additives Ex. 6-1 Ex. 6-2 6-1 6-2 Ex. 6-3 Hemp powder extract 6.34 6.34 6.34 6.34 6.34 Tween 80 1.60 1.60 1.60 1.60 1.60 Peppermint oil 1.01 1.01 1.01 1.01 1.01 Sweetener Adequate Adequate Adequate Adequate Adequate Silicon dioxide 0.00  0.075  0.375 0.5  6.25 HPMC & HPC 12.67  12.67  12.67  12.67  12.67  Purified water & ethanol To 100% Water-soluble polymer (HPMC & — 168.93:1 33.79:1 25.34:1 2.03:1 HPC):inorganic material (silicon dioxide) Disintegration 4 minutes About 3 Within 40 Within 20 About 1 or longer minutes seconds seconds minute Foreign body sensation in mouth 4   5   5   5   1   Flexibility Not Not Not Not Broken broken broken broken broken

TABLE-US-00008 TABLE 8 Comp. Comp. Example Example Comp. Additives Ex. 7-1 Ex. 7-2 7-1 7-2 Ex. 7-3 Hemp powder extract 6.34 6.34 6.34 6.34 6.34 Tween 80 1.60 1.60 1.60 1.60 1.60 Peppermint oil 1.01 1.01 1.01 1.01 1.01 Sweetener Adequate Adequate Adequate Adequate Adequate Talc 0.00  0.075  0.375 0.5  6.25 HPMC & HPC 12.67  12.67  12.67  12.67  12.67  Purified water & ethanol to 100% Water-soluble polymer (HPMC & — 168.93:1 33.79:1 25.34:1 2.03:1 HPC):inorganic material (talc) Disintegration 4 minutes About 3 Within 40 Within 30 About 1 or longer minutes seconds seconds minute Foreign body sensation in mouth 4   5   5   5   1   Flexibility Not Not Not Not Broken broken broken broken broken

TABLE-US-00009 TABLE 9 Comp. Comp. Example Example Comp. Additives Ex. 8-1 Ex. 8-2 8-1 8-2 Ex. 8-3 Hemp powder extract 6.34 6.34 6.34 6.34 6.34 Tween 80 1.60 1.60 1.60 1.60 1.60 Peppermint oil 1.01 1.01 1.01 1.01 1.01 Sweetener Adequate Adequate Adequate Adequate Adequate Calcium phosphate 0.00  0.075  0.375 0.5  6.25 HPMC & HPC 12.67  12.67  12.67  12.67  12.67  Purified water & ethanol to 100% Water-soluble polymer (HPMC & — 168.93:1 33.79:1 25.34:1 2.03:1 HPC):inorganic material (calcium phosphate) Disintegration 4 minutes About 3 Within 40 Within 30 About 1 or longer minutes seconds seconds minute Foreign body sensation in mouth 4   5   5   5   1   Flexibility Not Not Not Not Broken broken broken broken broken

{circle around (1)} Intraoral Disintegration Test

[0030] The intraoral disintegration rate of the prepared film was tested as follows. The films as described in Tables 6-9 were cult to a size of 37×27 mm and placed in the mouth of 10 adults. Then, the average time spent until the film was disintegrated by saliva was measured (Criterion of evaluation: The film should not be observed in the mouth, and 80% of the entire film should be dissolved, dispersed or disintegrated. The film weight should be 20% or less of the initial weight.).

{circle around (2)} Intraoral Foreign Body Sensation Test

[0031] Foreign body sensation in the mouth was tested after the disintegration of the film was completed. It was investigated whether foreign body sensation remains in the mouth after the intraoral disintegration test.

TABLE-US-00010 TABLE 10 Eval- Score uation Standard 1 Poor Very severe foreign body sensation and unpleasant taste remain in the mouth after disintegration of the film. 2 Not Severe foreign body sensation and unpleasant taste good remain in the mouth after disintegration of the film. 3 Not bad Slight foreign body sensation and unpleasant taste remain in the mouth after disintegration of the film. 4 Good No foreign body sensation but slight unpleasant taste remains in the mouth after disintegration of the film. 5 Excel- No foreign body sensation or unpleasant taste lent remains in the mouth after disintegration of the film.

TABLE-US-00011 TABLE 11 Comp. Comp. Comp. Comp. Comp. Comp. Additives Ex. A Ex. B Ex. C Ex. D Ex. E Ex. F Hemp extract 9.03 (hemp 9.03 (hemp 9.03 (hemp 9.03 (hemp 9.03 (hemp 9.03 (hemp oil extract) oil extract) oil extract) powder extract) powder extract) powder extract) Tween 80 1.98 1.98 1.98 1.98 1.98 1.98 Peppermint oil 0.94 0.94 0.94 0.94 0.94 0.94 Sweetener Adequate Adequate Adequate Adequate Adequate Adequate Water-insoluble 0.36 (chitin) 0.36 (chitosan) 0.36 (starch) 0.375 (chitin) 0.375 (chitosan) 0.375 (starch) excipient (organic material) HPMC & HPC 10.06  10.06  10.06  10.06  10.06  10.06  Purified water & To 100% ethanol Disintegration 3 minutes 3 minutes 3 minutes 3 minutes 3 minutes 3 minutes and 30 and 30 and 30 and 30 and 30 and 30 seconds seconds seconds seconds seconds seconds or longer or longer or longer or longer or longer or longer Foreign body 2   3   1   2   3   1   sensation in mouth Flexibility Broken Broken Not broken Broken Broken Not broken

[0032] As can be seen from Table 11, when organic materials of the same amount were added instead of the inorganic material, disintegration time was increased significantly, flexibility was decreased or strong foreign body sensation was felt in the mouth.

[0033] Orally disintegrating films with the compositions as described in Tables 12 and 13 were prepared based on the above experimental results.

TABLE-US-00012 TABLE 12 Addition amount Content Ingredients (mg)/unit (%) Purpose of addition Hemp oil extract 28.72 36.80 Main ingredient Peppermint oil 3.00 3.84 Flavoring agent Sucralose 4.00 5.12 Sweetener Neohesperidine 2.50 3.20 Sweetener Tween 80 6.30 8.07 Surfactant TiO.sub.2 1.13 1.45 Water-insoluble inorganic material Xanthan gum 0.40 0.51 Thickener HPMC 2910 5 cp 20.00 25.62 Excipient HPC-L 12.00 15.37 Excipient Total 78.05 mg 100%

TABLE-US-00013 TABLE 13 Addition amount Content Ingredients (mg)/unit (%) Purpose of addition Hemp powder extract 25.00 30.37 Main ingredient Peppermint oil 3.00 3.64 Flavoring agent Sucralose 4.00 4.86 Sweetener Neohesperidine 2.50 3.04 Sweetener Tween 80 6.30 7.65 Surfactant TiO.sub.2 1.13 1.37 Water-insoluble inorganic material Xanthan gum 0.40 0.49 Thickener HPMC 2910 5 cp 25.00 30.37 Excipient HPC-L 15.00 18.22 Excipient Total 82.33 mg 100%

[0034] The film formulations having the composition described in Tables 12 and 13 were disintegrated within 20 seconds in the mouth and showed superior film flexibility with little foreign body sensation after the disintegration.

INDUSTRIAL APPLICABILITY

[0035] The present disclosure provides an intraoral fast disintegrating formulation containing cannabidiol.

[0036] The present disclosure also provides a film-type fast disintegrating formulation containing a large quantity of cannabidiol, which is disintegrated fast in the mouth.