Enteric coating composition, enteric coating film, and preparation comprising same

Abstract

Disclosed are an enteric coating composition, an enteric coating film, and a preparation comprising same. The enteric coating composition according to an embodiment of the present disclosure comprises: hydroxypropyl methylcellulose phthalate (HPMCP); a plasticizer selected from triacetin or acetylated monoglyceride; a mixed solvent containing purified water and ethanol; and a PH adjuster for adjusting the pH to a range of 2.5 to 7.0, wherein the PH adjuster is sodium hydrogen carbonate ( NaHCO3).

Description

Enteric coating composition, enteric coating film and preparation containing the same

[0001] The present disclosure relates to an enteric coating composition, an enteric coating film, and a preparation comprising the same.

[0002] Enteric formulations are dosage forms designed to delay drug dissolution for a certain period of time after administration. They are generally manufactured using a special prescription or manufacturing method so that they do not disintegrate or dissolve for a certain period of time under gastric fluid conditions (around pH 1.2), but disintegrate and dissolve within a certain period of time under small intestinal fluid conditions (around pH 6.8).

[0003] Film coating is commonly used to manufacture enteric formulations. Depending on the solvent used, film coating can be categorized into aqueous and non-aqueous coatings. The former uses water as the solvent, while the latter uses a mixed solvent containing an organic solvent. Aqueous coatings offer economical and environmental advantages due to their low solvent usage, and unlike non-aqueous coatings (also known as oil-based coatings), they pose no risk of explosion. Examples of enteric soft capsule compositions using aqueous coatings are disclosed in Korean Patent No. 10-1380652, Korean Patent Publication No. 10-2015-0079282, and Korean Patent Publication No. 10-2020-0117883. However, aqueous coatings are performed at relatively high temperatures to evaporate moisture, which can significantly affect the formulation. Furthermore, they require a relatively long coating time compared to non-aqueous coatings. In particular, the long coating time limits productivity. This is why most companies manufacturing enteric formulations use non-aqueous coatings, despite their stability issues.

[0004] However, there is still room for improvement in the manufacturing of enteric formulations using non-aqueous coating methods. Enteric formulations require a higher coating volume than other coating formulations to ensure stable enteric properties. Consequently, the coating layer is relatively thick, requiring a long coating time. This high coating volume also increases product costs. Furthermore, when the process environment varies depending on the properties of the ingredients, it can be difficult to maintain consistent quality.

[0005] [Prior Art Literature]

[0006] Korean Patent No. 10-1380652 (registered on March 27, 2014)

[0007] Korean Patent Publication No. 10-2015-0079282 (published on July 8, 2015)

[0008] Korean Patent Publication No. 10-2020-0117883 (published on October 14, 2020)

[0009] The present disclosure provides an enteric coating composition, an enteric coating film, and a preparation including the same that can improve coating efficiency in a non-aqueous coating method.

[0010] According to one aspect of the present disclosure, an enteric coating composition may be provided, comprising: hydroxypropyl methylcellulose phthalate (HPMCP); a plasticizer selected from triacetin or acetylated monoglyceride; a mixed solvent comprising purified water and ethanol; and a pH adjuster for adjusting the pH to a range of 2.5 to 7.0, wherein the pH adjuster is sodium bicarbonate (sodium bicarbonate, NaHCO3).

[0011] At this time, it may be 50 to 150 parts by weight of hydroxypropyl methylcellulose phthalate (HPMCP), 125 to 210 parts by weight of purified water, 725 to 980 parts by weight of ethanol, 10 to 65 parts by weight of plasticizer, and 1 to 6 parts by weight of pH adjuster.

[0012] Additionally, the hydroxypropyl methylcellulose phthalate (HPMCP) may be selected from HPMPC-HP 50, HPMCP-HP 55, or HPMCP-HP 55S.

[0013] According to another aspect of the present disclosure, an enteric coating film formed from the above-described enteric coating composition can be additionally provided.

[0014] According to another aspect of the present disclosure, a formulation comprising the above-described enteric coating film can be additionally provided.

[0015] At this time, the formulation of the above preparation can be selected from among tablets, hard capsules, hollow hard capsules, and soft capsules.

[0016] When an enteric coating film is manufactured using an enteric coating composition according to the embodiments of the present disclosure, the coating speed can be increased compared to conventional non-aqueous coating methods, thereby shortening the coating time and reducing the coating amount, thereby improving coating efficiency. Furthermore, after the coating process, there is no clouding of the capsule surface or poor curing of the formulation.

[0017] Figure 1 (a) is a photograph of Comparative Example 1 in which a white cloud phenomenon occurred on the capsule surface and a photograph of Example 3 in which no white cloud phenomenon occurred, and Figure 1 (b) is a photograph in which it can be confirmed that the excipient formulation in Comparative Examples 1 and 2 was cured.

[0018] Figure 2 is a photograph of Comparative Example 1 in which a white clouding phenomenon occurred on the surface (joint) of an Omega 3 soft capsule, and a photograph of Example 3 in which no white clouding occurred.

[0019] Figure 3 is a photograph showing the separation state of the coated hard capsule in Example 5 after coating.

[0020] Hereinafter, the present disclosure will be described in detail with reference to the attached drawings. The following description should be understood as providing specific examples of the present disclosure, and the technical concepts of the present disclosure are not limited to the following description. Furthermore, the attached drawings are provided to aid understanding of the present disclosure, and the technical concepts of the present disclosure are not limited to the attached drawings.

[0021] Definition of Terms

[0022] The terms used in the description of the present disclosure may be defined as follows.

[0023] 'Enteric properties' may mean properties that do not disintegrate for more than 2 hours under in vitro gastric fluid conditions (pH 1.2) and disintegrate within 1 hour under in vitro intestinal fluid conditions (pH 6.8).

[0024] A "hard capsule" may refer to a formulation comprising a shell material composed of a pair of capsule substrates that are joined together, and a fill material filled inside the shell. Furthermore, a pair of capsule substrates that correspond to the shell material without fill material may also be included. In the latter case, the formulation may be referred to as an "empty capsule" or a "hollow hard capsule."

[0025] A 'soft capsule' may mean a liquid formulation comprising a single smooth shell material and a fill material filled inside the shell.

[0026] 'Tablet' can mean a preparation manufactured by compressing granules or powder into a certain shape.

[0027] Enteric coating composition

[0028] The present disclosure can provide an enteric coating composition. An enteric coating composition according to one embodiment of the present disclosure can include an enteric compound; a plasticizer; a mixed solvent including an organic solvent; and a pH regulator that increases the pH. The enteric coating composition can be used in the form of a solution, and is hereinafter referred to as an "enteric coating solution."

[0029] An enteric coating composition according to one embodiment of the present disclosure may include 50 to 150 parts by weight of an enteric compound, 125 to 210 parts by weight of purified water, 725 to 980 parts by weight of an organic solvent, 10 to 65 parts by weight of a plasticizer, and 1 to 6 parts by weight of a pH regulator.

[0030] The enteric compound may include hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), polyvinylacetate phthalate (PVAP), and copolymers of ethyl acrylate and ethyl methacrylate (Eudragit), derivatives of each of these, or mixtures thereof.

[0031] In one example, the enteric compound may be hydroxypropyl methylcellulose phthalate (hereinafter referred to as HPMCP). HPMCP is a type of cellulose derivative that is a major component of plant cell walls. HPMCP may be any commercially available product, and these commercial products may be classified into HPMCP-HP 50, HPMCP-HP 55, HPMCP-HP 55S, etc., depending on the viscosity of the HPMCP. The HPMCP usable in the enteric coating composition according to the embodiments of the present disclosure is not particularly limited, and a plurality of different HPMCP products may be mixed and used.

[0032] A plasticizer may serve to even out the surface of an enteric coating film formed using an enteric coating composition and prevent cracks from forming in the enteric coating film. In one example, the plasticizer may be selected from, but is not limited to, triacetin, acetylated monoglyceride, triethylene citrate, glycerin esters of fatty acids, or mixtures thereof.

[0033] In one example, the plasticizer may be a commercially available product, for example, Almax-5000 (product name), a commercial product of acetylated monoglyceride, may be used.

[0034] The mixed solvent may be an organic solvent or a mixed solvent containing an organic solvent. Here, the organic solvent may be at least one selected from the group consisting of acetone, ethanol, dichloromethane, dioxane, methanol, and isopropanol, but is not limited thereto.

[0035] In one example, the mixed solvent may be a mixed solvent of acetone and ethanol. In another example, the mixed solvent may refer to a solvent in which an organic solvent and water (specifically, purified water) are mixed, for example, a mixed solvent of water (purified water) and ethanol.

[0036] The pH adjusting agent can play a role of upwardly adjusting the pH of the enteric coating composition. More specifically, the pH adjusting agent can upwardly adjust the pH of the enteric coating composition to a range of about 2.5 to 7.0, more specifically to a range of about 2.5 to 6.8, and even more specifically to a range of about 2.8 to 6.8. The pH adjusting agent can be at least one selected from the group consisting of sodium hydroxide (NaOH), potassium hydroxide (KOH), ammonia, triethylamine (TEA), trimethylamine (TMA), ammonium bicarbonate ((NH4)HCO3), sodium bicarbonate (sodium bicarbonate, NaHCO3), sodium phosphate, tribasic sodium phosphate, disodium pyrophosphate, and sodium pyrophosphate. In one example, the pH adjusting agent can be sodium bicarbonate (sodium bicarbonate).

[0037] The present disclosure is characterized by using a pH adjuster to upwardly adjust the pH of an enteric coating solution when forming an enteric coating film using a non-aqueous coating method. As described above, the non-aqueous coating method has relatively higher productivity than the aqueous coating method, and is thus widely adopted by companies manufacturing enteric preparations. However, unlike the aqueous coating method, a pH adjuster has not been used in the past in the non-aqueous coating method. This is because enteric compounds do not dissolve well in water, but are relatively soluble in organic solvents. Therefore, while a pH adjuster has been used in the aqueous coating method to help the enteric compound dissolve in water, it is understood that the necessity of a pH adjuster has not been recognized in the existing oil-based coating method. However, the inventors of the present disclosure have discovered that, as in the aqueous coating method, when a pH adjuster is used to upwardly adjust the pH of the enteric coating solution in the oil-based coating method, the coating efficiency is increased, leading to the present disclosure.

[0038] Conventional non-aqueous coating methods are sensitive to the process environment (e.g., moisture, temperature, etc.), frequently resulting in cloudiness (a cloudy, turbid state) on the capsule surface after coating or poor curing of the formulation. For example, the pH of non-aqueous enteric coating solutions is approximately 2, and the presence of moisture often leads to incomplete film formation. However, increasing the drying temperature to remove moisture (e.g., above 35°C) can have a negative effect on the capsule contents (e.g., death of lactic acid bacteria if the contents are lactic acid bacteria). In contrast, lowering the drying temperature to minimize the effect on the capsule contents (e.g., below 25°C) can lead to excessively long coating times, which increases product costs and causes the formulation to harden. Furthermore, to ensure stable enteric properties (no disintegration for more than 2 hours at pH 1.2 in vitro), the coating film layer must be formed thickly, which increases coating time and the use of excessive raw materials, which in turn increases product costs. Against this backdrop, the embodiments of the present disclosure propose a method for using a pH regulator in a non-aqueous coating method. Using a pH regulator to increase the pH of an enteric coating solution, as described in the embodiments of the present disclosure, improves coating efficiency and minimizes the aforementioned problems. Furthermore, the embodiments of the present disclosure can be applied not only to hard capsules or tablets, but also to soft capsules and hollow hard capsules. This will be described in more detail in the test examples described below.

[0039] Meanwhile, the enteric coating composition according to the embodiments of the present disclosure may further include additives commonly used in the art, such as lubricants, surfactants, sweeteners, pigments (colorants), and antifoaming agents, in amounts commonly used, as needed. Such additives may be used alone or in combination of two or more.

[0040] The above-described long-lasting coating composition can be manufactured by the following method.

[0041] In one embodiment, the enteric coating composition can be prepared by dissolving a pH adjuster in purified water, adding ethanol and a plasticizer, and then dissolving the enteric compound.

[0042] More specifically, the enteric coating composition can be prepared by dissolving sodium bicarbonate (sodium bicarbonate) in purified water, adding ethanol and an acetylated monoglyceride as a plasticizer, and then dissolving HPMCP. The amount of each component added can vary depending on the composition of the enteric coating composition described above.

[0043] In another embodiment, the enteric coating composition may be prepared by simultaneously dissolving an enteric compound, a plasticizer, and a pH regulator in a mixed solvent comprising purified water and an organic solvent. The amount of each component added may vary depending on the composition of the enteric coating composition described above.

[0044] Meanwhile, in the method for manufacturing the above-described long-lasting coating composition, dissolution or mixing of each component can be accomplished through a conventional stirring device.

[0045] Enteric coating film

[0046] The present disclosure can additionally provide an enteric coating film prepared using the enteric coating composition described above. The enteric coating film can be prepared by forming the enteric coating composition described above into a solution (enteric coating solution), coating the solution onto a dosage form such as a tablet or capsule, and drying the solution.

[0047] Enteric coating films according to embodiments of the present disclosure may include an enteric compound, a pH regulator, and a plasticizer. Furthermore, the enteric coating film may further include additives commonly used in the art, such as lubricants, surfactants, sweeteners, pigments, and antifoaming agents, as needed.

[0048] Meanwhile, conventional coating methods can be used to coat an enteric coating composition onto a dosage form such as a tablet or capsule. For example, spray coating can be performed using a coating device such as a pan coating device, a drum-type coating device, a fluidized bed coating device, a stirred fluidized coating device, or a motorized fluidized coating device. Examples of spray coating devices include, but are not limited to, an air spray device. In addition, the drying conditions after coating are not particularly limited and can be performed to a degree that can maintain the dry state required for the final product.

[0049] When an enteric coating film is manufactured using an enteric coating composition according to embodiments of the present disclosure, the coating speed (meaning the spraying speed of the enteric coating solution) can be faster than with conventional non-aqueous coating methods, thereby shortening the coating time (meaning the spraying time of the enteric coating solution) and reducing the total spraying amount (meaning the total spraying amount of the enteric coating solution). In addition, since the white turbidity phenomenon on the capsule surface or the poor curing of the formulation do not occur after the coating process, the coating efficiency can be improved while maintaining the coating quality of the hard capsule. Furthermore, when applied to soft capsules, coating is possible even at temperatures below 20°C, especially at 10°C, thereby maintaining the coating quality and improving the stability of the formulation. In addition, when applied to hollow hard capsules, coating quality at a commercially available level can be maintained similarly when coating with a coater and a fluidized bed granulator.

[0050]

[0051] Preparations containing enteric coating films

[0052] The present disclosure can additionally provide a formulation comprising the enteric coating film described above. The formulation according to the present disclosure may be a pharmaceutical formulation or a food formulation. Furthermore, the formulation according to the present disclosure may include, but is not limited to, a tablet, a hard capsule, a hollow hard capsule, or a soft capsule. Furthermore, the size of the tablet or capsule described above may be the size of a commonly distributed tablet or capsule.

[0053] The contents of the formulation according to the present disclosure are not particularly limited. For example, the contents may include all raw materials, nutritional ingredients, and separately approved raw materials registered in the Health Functional Food Codex as main ingredients of health functional foods. Even if the formulation is not a health functional food, it may include edible oils and fats as general foods.

[0054] In addition, the form of the contents is not particularly limited and may be, for example, liquid contents, suspension contents, or solubilizer contents. More specifically, i) Liquid contents such as oils include EPA and DHA-containing fats and oils for health functional foods, gamma-linolenic acid-containing fats, krill oil and hemp seed oil for general foods, choline alphoseraide and cucurbit seed oil for pharmaceuticals, etc., and such ingredients are not particularly limited. ii) Suspension contents in which a particle-containing powdered ingredient is mixed with an oil-based excipient include milk thistle, red ginseng, hyaluronic acid, aloe gel, etc. for health functional foods, and magnesium oxide, ursodexoxycholic acid, bilberry dry extract, etc. for pharmaceuticals, and such ingredients are not particularly limited. In addition, iii) the contents in the form of a viscous substance in powder or lump form dissolved in a solvent may include plant sterols and phosphatidylserine for health functional foods, and acetaminophen, naproxen, ibuprofen for pharmaceuticals, etc., and such ingredients are not particularly limited.

[0055] Furthermore, the contents may be substances that cause bad breath or discoloration when digested in the stomach, such as algae omega-3 oil, refined fish oil, garlic, vitamin B1, various egg oils, etc. depending on the purpose of the intestinal properties, or intestinal bacteria that are weak to acids, such as bifidobacteria, ingredients that irritate the stomach, such as capsaicin, iron agents, such as ferrous fumarate and dried iron sulfate, antipyretics, analgesics, anti-inflammatory agents, antitumor agents, antibacterial agents, etc., which are intended to have a long-term effect, but are not limited thereto.

[0056]

[0057] Exam example

[0058] Hereinafter, the present disclosure will be described in more detail through test results of examples and comparative examples. However, the present disclosure is not limited to the following examples.

[0059] (1) Manufacturing and testing of hard capsules

[0060] Classification Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 HPMCP (HP55) 12.0 wt% 12.0 wt% 12.0 wt% 12.0 wt% 12.0 wt% 12.0 wt% Purified water 12.81 wt% 12.79 wt% 12.75 wt% 12.6 wt% 12.82 wt% 12.68 wt% Ethanol 74.09 wt% 73.97 wt% 73.85 wt% 73.0 wt% 74.13 wt% 73.62 wt% Plasticizer 1.0 wt% (Almax) 1.0 wt% (Triacetin) 1.0 wt% (Almax) 2.4 wt% (Almax)1.0wt%(Almax)1.0wt%(Almax)Sodium bicarbonate(sodium bicarbonate)0.10wt%0.24wt%0.40wt%-0.05wt%0.7wt%Total100wt%100.0wt%100.0wt%100wt%100wt%pH2.83.66.51.52.17.5

[0061] Enteric coating solutions corresponding to Examples 1 to 3 and Comparative Examples 1 to 3 were prepared with the compositions shown in [Table 1] above. In Comparative Example 1, sodium bicarbonate (pH adjuster) was not added. Almax-5000 (Ilshin Wells) was used as a plasticizer (triacetin was used in Example 2), and HP55 (Lotte Fine Chemical) was used as HPMCP. The enteric coating solution was prepared by first dissolving sodium bicarbonate (sodium bicarbonate) in purified water (except Comparative Example 1), then adding ethanol and a plasticizer, and then dissolving HPMCP, and the amounts added are as shown in [Table 1].

[0062] Next, 250 mg of excipients (lactose:crystalline cellulose:maltodextrin = 1:1:1) were filled into HPMC hard capsules (No. 2), and the enteric coating solutions according to the examples and comparative examples were coated using a commercial coating machine (Sejong Pharmatech C30FC product; equipment conditions: spray nozzle 0.8Φ, air 25-38 L / min). At this time, the coating conditions (spray speed, temperature, and spray time) that allowed normal coating were recorded, and the coating amount per capsule weight was calculated based on the coating conditions.

[0063] For the coated hard capsules, 1) appearance quality inspection, 2) filler (lactic acid bacteria) inspection, and 3) disintegration test were conducted, and the results are summarized in [Table 2] below. The appearance quality inspection focused on whether the capsule exterior had a cloudy appearance, and the filler inspection focused on whether the filler had hardened. The disintegration test (1st solution, 2nd solution) was conducted according to the provisions of the Health Functional Food Codex Test Method.

[0064] ClassificationExample 1Example 2Example 3Comparative Example 1Comparative Example 2Comparative Example 3Coating ConditionsSpray Speed ​​(rpm)17~2017~2012~1412~1417~2021~23Exhaust Air Volume (rpm)1,8001,8002,0002,0001,8001,800Supply Air Volume (rpm)1,4001,4001,5001,5001,4001,400Supply / Exhaust Temperature (℃)85 / 3385 / 3385 / 3585 / 3585 / 3385 / 32Spray Time45 min45 min400 min400 min45 min40 minCoating Amount (Compared to Capsule Weight)35%35%35%100%100%35%Appearance Quality Inspection Suitable Suitable Suitable Occurrence (turbidity) Occurrence (turbidity) Suitable Filling material Inspection Suitable Suitable Suitable Curing Suitable Disintegration 1st liquid test (pH 1.2, 2 hours) Suitable Suitable Suitable Suitable Suitable Unsuitable (disintegration) Disintegration 2nd liquid test (pH 6.8, within 60 minutes) Suitable Suitable Suitable Suitable Suitable Suitable

[0065] Referring to [Table 2], the hard capsules coated with the enteric coating solutions corresponding to Examples 1 to 3 were found to be suitable in all of the appearance quality inspection, filler inspection, and disintegration test. However, when the pH adjuster was not added as in Comparative Example 1, or when a smaller amount of the pH adjuster was added than in the Examples as in Comparative Example 2, a white clouding phenomenon appeared on the capsule surface, and a problem occurred in which the excipients hardened. In this regard, Fig. 1 (a) shows a photograph of Comparative Example 1 in which a white clouding phenomenon occurred on the capsule surface and a photograph of Example 3 in which no white clouding occurred, and Fig. 1 (b) shows a photograph confirming that the excipients in Comparative Examples 1 and 2 were hardened. On the other hand, when the pH adjuster was added in an excess amount than in the Examples as in Comparative Example 3, there were no abnormalities in the appearance quality and filler, but it was confirmed that the capsules disintegrated within 2 hours in the first solution disintegration test, which was unsuitable.

[0066] In particular, when comparing the coating conditions and coating amount, in the case of the enteric coating solution corresponding to Examples 1 to 3, the spraying speed was increased and the temperature was somewhat lowered compared to Comparative Examples 1 to 2, so it was confirmed that the spraying time was greatly reduced, and accordingly, the coating amount was also confirmed to be greatly reduced.

[0067]

[0068] (2) Manufacturing and testing of soft capsules

[0069] Enteric coating solutions corresponding to Examples 1 to 3 and Comparative Examples 1 to 3 described in [Table 1] above were prepared and coated onto Omega-3 soft capsules (Ovlong 15, 750 mg) using a commercial coating machine (C30FC product of Sejong Pharmatech). At this time, the coating temperature at which normal coating was possible was recorded, and the coated hard capsules were subjected to an appearance quality inspection and a disintegration test, and the results are summarized in [Table 3] below.

[0070] ClassificationExample 1Example 2Example 3Comparative Example 1Comparative Example 2Comparative Example 3Coating temperature (℃)151510303030Quality (appearance cloudiness, etc.)SuitableSuitableSuitable Occurrence (cloudiness) Occurrence (cloudiness)SuitableDisintegration 1st liquid test (pH 1.2, 2 hours)SuitableSuitableSuitableSuitableNot suitableDisintegration 2nd liquid test (pH 6.8, within 60 minutes)SuitableSuitableSuitableSuitable

[0071] Referring to [Table 3], the enteric coating solutions of Examples 1 to 3 were found to be suitable in both the appearance quality inspection and the disintegration test when coating soft capsules. However, when no pH adjuster was added to the enteric coating solution, as in Comparative Example 1, or when a smaller amount of pH adjuster was added than in the Examples, as in Comparative Example 2, a problem occurred in which a white clouding phenomenon appeared on the capsule surface. In this regard, Fig. 2 shows a photograph of Comparative Example 1 in which a white clouding phenomenon occurred on the surface (joint) of an Omega 3 soft capsule and a photograph of Example 3 in which no white clouding occurred. On the other hand, when a pH adjuster was added in excess of the Examples, as in Comparative Example 3, there was no problem with the appearance quality, but it was found to be unsuitable in the first disintegration solution test.

[0072] In particular, when soft capsules were coated with the enteric coating solutions corresponding to Examples 1 to 3, it was confirmed that coating was possible even at low temperatures of 10 to 15°C. Therefore, it was found that the embodiments of the present disclosure could prevent the white clouding phenomenon that may occur in the coating film even in soft capsules, and could improve the stability of liquid formulations by enabling coating at low temperatures of 20°C or lower.

[0073]

[0074] (3) Test by hard capsule coating machine

[0075] Classification Example 4 Example 5 Comparative Example 4 HPMCP (HP50) 5.0 wt% 5.0 wt% 5.0 wt% Purified water 13.82 wt% 17.00 wt% 13.92 wt% Ethanol 79.98 wt% 72.50 wt% 80.08 wt% Plasticizer 1.0 wt% (Almax) 5.0 wt% (Almax) 1.0 wt% (Almax) Sodium bicarbonate (baking soda) 0.2 wt% 0.5 wt% - Total 100.0 wt% 100.0 wt% 100.0 wt% pH 4.5 6.5 1.5

[0076] In order to determine whether there is a difference in coating quality depending on the type of commercial coating machine, enteric coating solutions corresponding to Examples 4, 5, and Comparative Example 4 were prepared. Almax-5000 (Ilshin Wells) was used as the plasticizer, and HP50 (Lotte Fine Chemical) was used as the HPMCP.

[0077] Next, hollow hard capsules (HPMC white capsules #0) were prepared, and 3,000 capsules were coated using a fully punched commercial coating machine (C30FC product of Sejong Pharmatech; equipment conditions: spray nozzle 0.8Φ, air 25-38 L / min) and a fluidized bed coater (DPL-1 product of Chinese company; equipment conditions: spray nozzle 2.0Φ). At this time, the coating conditions (spray speed, temperature, and spray time) that allowed normal coating were recorded, and the coating amount per capsule weight was calculated based on the coating conditions.

[0078] For the coated hard capsules, an appearance quality inspection and a disintegration test were conducted, and the results are summarized in [Table 5] below. The appearance quality inspection focused on whether or not the capsule exterior had a cloudy appearance, and the disintegration test (1st solution, 2nd solution) was conducted according to the provisions of the Health Functional Food Codex Test Method. For the disintegration test, 500 mg of excipients (lactose:crystalline cellulose:maltodextrin = 1:1:1) were filled as contents.

[0079] ClassificationExample 4Example 5Comparative Example 4Coating Machine TypeSejong Pharmatech C30FCFluidized Bed Coating MachineDPL-1Fluidized Bed Coating MachineDPL-1Sejong Pharmatech C30FCFluidized Bed Coating MachineDPL-1Coating ConditionsInjection Speed ​​(rpm)17~207~117~1112~147~11Exhaust Air Volume (rpm)2,000--1,900-Supply Air Volume1,600rpm23~40Hz23~40Hz1,400rpm23~40HzSupply / Exhaust Temperature (℃)100 / 35Inlet 50 / Product 37Inlet 50 / Product 37100 / 35Inlet 50 / Product 37 Spray time 45 minutes 120 minutes 120 minutes 60 minutes 120 minutes Coating amount (compared to capsule weight) 40% 20% 20% 40% 20% Quality (white turbidity, etc.) Suitable Suitable Suitable Inappropriate Inappropriate Disintegration 1st liquid test (pH 1.2, 2 hours) Suitable Suitable Suitable Inappropriate Inappropriate Disintegration 2nd liquid test (pH 6.8, within 60 minutes) Suitable Suitable Suitable Suitable Suitable

[0080] Referring to [Table 5], all of the hollow hard capsules coated with the enteric coating solutions corresponding to Comparative Example 4, Example 4, and Example 5 were well coated. However, in the case of Comparative Example 4, the enteric material was not well settled on the surface of the hollow hard capsule, so the appearance quality was unsuitable, and it was confirmed to be unsuitable in the first disintegration liquid test. On the other hand, in the case of Example 4 or Example 5, the enteric material was well settled on the surface of the hollow hard capsule, so the appearance quality was suitable, and it was confirmed to be suitable in the disintegration test. In this regard, FIG. 3 is a photograph showing the separated state of the hollow hard capsule coated in Example 5 after coating. That is, it was confirmed that the enteric coating solution according to the embodiment of the present disclosure had good coating quality even when applied to hollow hard capsules in a commonly used commercial coating machine (a fully punched commercial coater, a fluidized bed coater), and thus it was confirmed that it is commercially usable.

[0081] The embodiments of the present disclosure have been described above. However, those skilled in the art will appreciate that various modifications to the present disclosure, such as simple design changes, omission of certain components, and simple changes in purpose, can be made within the scope of the technical concepts of the present disclosure as defined in the claims, depending on specific applications of the technology. It is self-evident that such modifications also fall within the scope of the present disclosure.

Claims

1. Hydroxypropyl methylcellulose phthalate (HPMCP); A plasticizer selected from triacetin or acetylated monoglyceride; A mixed solvent containing purified water and ethanol; and Contains a pH regulator that adjusts the pH to a range of 2.5 to 7.0, An enteric coating composition wherein the pH adjusting agent is sodium bicarbonate (sodium bicarbonate, NaHCO3).

2. In claim 1, An enteric coating composition comprising 50 to 150 parts by weight of hydroxypropyl methylcellulose phthalate (HPMCP), 125 to 210 parts by weight of purified water, 725 to 980 parts by weight of ethanol, 10 to 65 parts by weight of a plasticizer, and 1 to 6 parts by weight of a pH regulator.

3. In claim 1, An enteric coating composition wherein the above hydroxypropyl methylcellulose phthalate (HPMCP) is selected from HPMPC-HP 50, HPMCP-HP 55 or HPMCP-HP 55S.

4. An enteric coating film formed with an enteric coating composition according to any one of claims 1 to 3.

5. A preparation comprising an enteric coating film according to claim 4.

6. In claim 5, The formulation of the above preparation is a preparation selected from among tablets, hard capsules, hollow hard capsules and soft capsules.

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