Application of edible oil in production of vitamin D drops

Abstract

This invention relates to the application of edible oils in the production of vitamin D drops, belonging to the field of pharmaceutical preparation technology. This invention uses specific types of edible oils (such as medium-chain triglycerides) as lubricants in the vitamin D drop pelleting process, which can completely solve the problem of liquid paraffin in vitamin D drops while ensuring pellet quality. Among single edible oils, medium-chain triglycerides and soybean oil produce the best pellet quality, while using a combination of medium-chain triglycerides and soybean oil can further improve pellet quality.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation production technology, specifically relating to the application of edible oil in the production of vitamin D drops. Background Technology

[0002] Vitamin D drops are commonly used clinically to prevent and / or treat vitamin D deficiency in children and adolescents at risk of developing the condition, to prevent vitamin D deficiency in adults, pregnant women, and lactating women at risk of developing the condition, and as an adjunct to specific treatments for vitamin D deficiency or osteoporosis at risk of vitamin D deficiency. The contents of vitamin D drops are primarily composed of vegetable oil and vitamin D, while the capsule shell is mainly composed of gelatin, glycerin, and water. The main equipment used to prepare vitamin D drops includes a gel filling and soft capsule machine.

[0003] Liquid paraffin is a common lubricant in soft capsule machines, often used as a release agent to prevent adhesion between the capsule film and the mold / pressure rollers. Throughout the capsule compression process, liquid paraffin is contained in an oil box and continuously circulated through pipelines to ensure lubrication between the capsule film and the mold / pressure rollers. Therefore, paraffin is carried into both the inner and outer surfaces of the vitamin D drops during compression, and the contents of the vitamin D drops also contain a small amount of liquid paraffin. Because liquid paraffin has a lubricating effect and can cause a laxative effect when ingested, and since the primary population taking vitamin D drops is children, including infants under 100 days old, whose constitutions are more sensitive, excessive intake of liquid paraffin may lead to symptoms such as allergies, skin itching, and diarrhea. The safety of liquid paraffin is also a concern. The residual amount of liquid paraffin has become one of the indicators that need to be strictly controlled in pharmaceutical preparations. The strictest requirement from the FDA is that the lubricant impurity content be <0.8 mg / capsule, or less than 0.2% based on the contents.

[0004] Existing technologies have studied how to reduce the liquid paraffin content in the preparation of vitamin D drops using edible oil as a lubricant. To remove residual liquid paraffin from the surface of soft capsules, a specialized soft capsule cleaning process is typically required. For example, patent (CN208942915U) proposes a rotating drum device for soft capsules that eliminates the need for cleaning. This device uses a frame, a mesh cage, crossbars, and an oil-absorbing cloth to clean the oil from the soft capsule surface. Specifically, during the soft capsule shaping process, the oil-absorbing cloth removes residual liquid paraffin, eliminating the need for ethanol cleaning and allowing direct drying. Journal articles (“Structure, Principle, and Application of Roller-Type Soft Capsule Making Machine in Traditional Chinese Medicine Preparation Production,” Wei Zengyu et al., *Mechanical and Electrical Information*, 2013, Issue 35) disclose the use of anhydrous ethanol to wash away the lubricating oil from the surface of newly formed soft capsules before drying. Using oil-absorbing cloths for cleaning creates blind spots and fails to remove residual liquid paraffin from inside the softgels. While using solvents like anhydrous ethanol to remove the liquid paraffin poses safety hazards in the production environment, the softgels become hard and brittle after ethanol soaking or washing, affecting their usability. Furthermore, the residual liquid paraffin inside the softgels is difficult to remove completely. Therefore, current technology cannot effectively control the liquid paraffin content in vitamin D drops and cannot completely solve the problem of liquid paraffin in vitamin D drops.

[0005] Furthermore, most of the existing methods for detecting liquid paraffin involve the food industry and employ gas chromatography. However, when using gas chromatography to determine droplet samples, the edible oils in the soft capsule contents can interfere with the determination of liquid paraffin, thus posing significant problems in terms of measurement accuracy and making quantitative detection impossible.

[0006] Based on this, the present invention, in addition to the quantitative detection of liquid paraffin in general processes, further uses edible oil as a lubricant to prepare vitamin D drops, so as to completely solve the problem of liquid paraffin in vitamin D drops and meet the requirements of large-scale production and commercial application. Summary of the Invention

[0007] This invention addresses the problems of existing technologies by proposing the application of edible oils in the production of vitamin D drops. This invention uses specific types of edible oils (such as medium-chain triglycerides) as lubricants during the vitamin D drop pelleting process, which can completely solve the problem of liquid paraffin in vitamin D drops while ensuring pelleting quality. Among single edible oils, medium-chain triglycerides and soybean oil produce the best pelleting quality, and using medium-chain triglycerides and soybean oil can further improve pelleting quality.

[0008] To achieve the above objectives, in a first aspect, the present invention provides the application of edible oil in the production of vitamin D drops. Vitamin D drops are produced using a soft capsule machine, and in the capsule pressing process, edible oil is used as a lubricant to lubricate the capsule shell and complete the subsequent capsule pressing process. The edible oil is selected from at least one of medium-chain triglycerides, olive oil, rapeseed oil, soybean oil, and peanut oil.

[0009] In a preferred embodiment, the medium-chain glyceride is selected from at least one of medium-chain monoglycerides, medium-chain diglycerides, and medium-chain triglycerides.

[0010] In a preferred embodiment, the edible oil is selected from at least one of medium-chain triglycerides, olive oil, rapeseed oil, soybean oil, and peanut oil, more preferably medium-chain triglycerides and / or soybean oil.

[0011] In a preferred embodiment, the edible oil is a mixture of medium-chain triglycerides and soybean oil; wherein the mass ratio of medium-chain triglycerides to soybean oil is preferably 1:0.8-1.5, more preferably 1:1.0-1.5, and most preferably 1:1.2-1.5.

[0012] In a preferred embodiment, the density of the edible oil is 0.60-0.95.

[0013] In a preferred embodiment, the vitamin D drops include a contents and a gel; wherein the contents of the vitamin D drops are made from edible oil and vitamin D, and the gel of the vitamin D drops is made from gelatin, glycerin, and purified water; the edible oil in the contents includes at least one of medium-chain triglycerides, olive oil, rapeseed oil, soybean oil, and peanut oil, and the medium-chain triglycerides include at least one of medium-chain monoglycerides, medium-chain diglycerides, and medium-chain triglycerides.

[0014] In a preferred embodiment, the specific process for producing vitamin D drops using a soft capsule machine is as follows:

[0015] 3) Glue preparation: The raw materials for the vitamin D drops are prepared into a glue solution in a glue preparation tank;

[0016] 4) Solution preparation: Mix the raw materials of the vitamin D drops evenly to obtain the solution to be pressed;

[0017] 3) Capsule pressing: The gelatinous liquid from step 1) and the liquid to be pressed from step 2) are pressed into wet capsules using a capsule machine.

[0018] 4) Shaping and drying.

[0019] In a preferred embodiment, the specific process of shot pressing in step 3) is as follows: set the temperature of the glue barrel to 50-70℃, the temperature of the glue storage box to 50-70℃, the temperature of the spray body to 35-45℃, and the temperature of the cold air to 16-20℃. After the temperature reaches the set temperature, compressed air is introduced into the glue barrel to press out the glue liquid prepared in step 1). The switch of the oil tank containing edible oil is opened to lubricate the rubber. The main unit is turned on, the mold speed is set, the rubber is pulled taut and placed in the track, the thickness of the rubber is adjusted, the mold is pressed, the spray body is lowered, and the medicine liquid to be pressed prepared in step 2) is poured in. After the temperature of the spray body stabilizes, the spray body valve is opened, the spray body temperature is adjusted to make the joint line flat and leak-proof, and the loading amount is adjusted to 0.242g-0.258g.

[0020] In a preferred embodiment, the shot blasting process further includes a step of spraying edible oil onto the uneven areas of the rubber sheet to make the rubber sheet smoother and more effectively encapsulate the contents.

[0021] Secondly, the present invention provides a method for detecting lubricating oil impurities in vitamin D drops, which employs high performance liquid chromatography (HPLC). The chromatographic column is a column packed with octadecylsilane-bonded silica gel, and isocratic elution is performed using a non-polar solvent as the mobile phase. The non-polar solvent is selected from at least one of n-heptane, n-hexane, ethyl acetate, and isopropanol, more preferably n-heptane or n-hexane, and most preferably n-heptane.

[0022] In a preferred embodiment, the chromatographic column is a C18 column, more preferably an Agilent 1 C18 column; the column parameters are preferably 4.6 mm × 150 cm and 5 μm.

[0023] In a preferred embodiment, the column temperature is 30-50°C, more preferably 35-45°C, and most preferably 40°C.

[0024] In a preferred embodiment, the flow rate is 0.8-1.2 ml / min, more preferably 0.9-1.1 ml / min, and most preferably 1.0 ml / min.

[0025] In a preferred embodiment, the detector is a differential detector.

[0026] In a preferred embodiment, the detector temperature is 30-50°C, more preferably 40-50°C, and most preferably 45°C.

[0027] In a preferred embodiment, high performance liquid chromatography is used, with a differential detector, a C18 column, column parameters of 4.6 mm × 150 cm, 5 μm, isocratic elution with n-heptane as the mobile phase, column temperature of 40 °C, flow rate of 1.0 ml / min, and injection volume of 20 μL.

[0028] The "soybean oil" mentioned in this invention refers to a fatty oil extracted from the seeds of soybean (Glycine max (L.) Merr.), a legume.

[0029] The "gelatin" mentioned in this invention refers to a product obtained by purifying collagen from animal skin, bones, tendons and ligaments after incomplete acid hydrolysis, alkaline hydrolysis or enzymatic degradation, or a mixture of the above three different gelatin products.

[0030] The "medium-chain triglyceride" mentioned in this invention refers to caprylic acid (C8H2O) isolated from the fatty oil extracted from the hard, dried portion of the endosperm of coconut (Cocos nucifera L.) or oil palm (Elaeis guineensis Jacq). 16 O2), decanoic acid (C 10 H 20 A mixture of triglycerides obtained by esterification of saturated fatty acids such as O2 with glycerol. Contains caprylic acid (C8H2O). 16 O2) and decanoic acid (C 10 H 20 The total amount of O2 must not be less than 95.0%.

[0031] The "olive oil" mentioned in this invention refers to a fatty oil extracted from the ripe drupe of the olive tree.

[0032] The "peanut oil" mentioned in this invention refers to a fatty oil refined from the mature seeds of the legume plant Arachis hypogaea L. or its varieties.

[0033] The "coconut oil" mentioned in this invention refers to a fatty oil refined from the seeds of the coconut palm, a plant of the palm family.

[0034] The "liquid paraffin" mentioned in this invention refers to a mixture of various liquid saturated hydrocarbons obtained from petroleum.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. This invention uses specific types of edible oils (such as medium-chain triglycerides) as lubricants in the vitamin D drop pelleting process, which can completely solve the problem of liquid paraffin in vitamin D drops while ensuring pelleting quality. Among single edible oils, medium-chain triglycerides and soybean oil produce the best pelleting quality, and using medium-chain triglycerides and soybean oil can further improve pelleting quality.

[0037] 2. The application of edible oil in the production of vitamin D drops provided by this invention can guarantee and improve product quality and ensure medication safety. The method is simple, highly operable, and has high industrialization feasibility, and has already achieved industrial production and commercial application.

[0038] 3. The method for detecting the liquid paraffin content in vitamin D drops provided in the basic embodiment 3 of the present invention can achieve quantitative detection of liquid paraffin, and can quickly, effectively and accurately detect the content of liquid paraffin, thereby ensuring the safety and effectiveness of clinical medication. Attached Figure Description

[0039] Figure 1 The chromatogram of the vitamin D drops prepared in Basic Example 4, wherein peak 1 is the peak of liquid paraffin. Detailed Implementation

[0040] The following embodiments illustrate the invention in more detail, but do not limit the invention in any way.

[0041] The following sources of raw materials are provided as examples:

[0042] Medium-chain triglycerides: purchased from Jiangxi Alpha High-Tech Pharmaceutical Co., Ltd.;

[0043] Olive oil: purchased from Tianjin Xincheng Kangda Pharmaceutical Co., Ltd.

[0044] Rapeseed oil: purchased from Zhongnuo Kailin Pharmaceutical Development (Suzhou) Co., Ltd.;

[0045] Soybean oil: purchased from Shandong Ruisheng Pharmaceutical Excipients Co., Ltd.

[0046] Peanut oil: pharmaceutical grade, purchased from Hubei Gedian Renfu Pharmaceutical Excipients Co., Ltd.;

[0047] Coconut oil: food grade, purchased from Jinan Xinjiulong Biotechnology Co., Ltd.

[0048] Liquid paraffin: purchased from Shandong Ruisheng Pharmaceutical Excipients Co., Ltd.;

[0049] Gelatin: Purchased from Hunan Ercon Gelatin Co., Ltd.;

[0050] All other raw materials are commercially available.

[0051] The capsule machine mentioned in the examples and comparative examples is a fully automatic soft capsule machine of model YWJ100-Ⅱ, purchased from Beijing Xinhangcheng Technology Development Co., Ltd.

[0052] Basic Example 1 uses liquid paraffin as a lubricant to produce vitamin D drops.

[0053] Formulation (for production of 10,000 tablets)

[0054]

[0055]

[0056] Preparation process:

[0057] (I) Glue making

[0058] 1) Add the prescribed amount of glycerin and water to the gelling tank, turn on the stirrer, and set the temperature of the gelling tank to 75℃.

[0059] 2) When the temperature inside the gelatin dissolving tank reaches the set temperature, stop stirring, add the prescribed amount of gelatin, and then start stirring again. At the same time, evacuate to -0.05 to -0.06 MPa and maintain negative pressure stirring for 30 minutes.

[0060] 3) Adjust the set temperature of the gelling tank to 60℃, turn on the vacuum pump and evacuate for 45 minutes, stirring continuously during the evacuation process;

[0061] 4) Turn off the vacuum pump, stop stirring, open the atmospheric connection valve, keep at 60°C and let stand to degas. Let stand to obtain the adhesive solution.

[0062] (II) Solution Preparation

[0063] Add the prescribed amount of vitamin D to soybean oil and stir until well mixed at room temperature to obtain the medicine solution to be pressed.

[0064] (III) Shot Pressing

[0065] After installing and starting the capsule machine, connect the heating cable and heating rod and preheat them. Set the temperature of the glue tank to 60℃, the temperature of the glue storage box to 60℃, the temperature of the spray body to 40℃, and the temperature of the cold air to 18℃. After the temperature reaches the set temperature, introduce compressed air into the glue tank to press out the glue liquid prepared in step (I). Open the switch of the oil tank containing liquid paraffin oil to lubricate the rubber. Turn on the main unit, set the mold speed, tighten the rubber and place it in the track, adjust the thickness of the rubber, press the mold, lower the spray body, and pour in the medicine liquid to be pressed prepared in step (II). After the spray body temperature stabilizes, open the spray body valve, adjust the spray body temperature to make the seam line flat and leak-proof, and adjust the filling amount to 0.242g-0.258g. When pressing, discard the capsules pressed out when the spray body temperature fluctuation is > ±0.3℃.

[0066] (iv) Shaping and drying

[0067] The compressed capsules were first shaped in a rotating drum for 20 minutes, and then dried overnight in a perforated tray. The first-pass yield was 94.3%.

[0068] Basic Example 2 uses methanol as the mobile phase to determine the content of liquid paraffin in vitamin D drops. Analytical conditions:

[0069] Equipment: High performance liquid chromatograph, detector is differential detector;

[0070] Column: Agilent 1 C18 (4.6 mm × 250 cm, 5 μm);

[0071] Mobile phase: methanol;

[0072] Flow rate: 1 mL / min;

[0073] Elution method: isocratic elution;

[0074] Running time: 10 minutes;

[0075] Column temperature: 40℃;

[0076] Detector temperature: 45℃;

[0077] Injection volume: 20 μL.

[0078] Preparation of the test solution: Accurately weigh 1.0 g of the contents of Basic Example 1, place it in a 5 mL volumetric flask, dissolve it in methanol and dilute to the mark, shake well, and the solution is ready.

[0079] Preparation of reference solution: Accurately weigh / transfer the liquid paraffins shown in Table 1, place them in a 20 mL volumetric flask, dissolve them in methanol and dilute to the mark, shake well to obtain the reference stock solution.

[0080] Table 1

[0081]

[0082] The test solution and reference solution were precisely measured and injected into the liquid chromatograph, and the chromatograms were recorded. However, no peaks were detected in the chromatograms. Therefore, the detection method was improved.

[0083] Basic Example 3 uses n-heptane as the mobile phase to determine the liquid paraffin content in vitamin D drops.

[0084] (1) Analysis conditions:

[0085] Equipment: High performance liquid chromatograph, detector is differential detector;

[0086] Column: Agilent 1 C18 (4.6 mm × 250 cm, 5 μm);

[0087] Mobile phase: n-Heptane;

[0088] Flow rate: 1.0 mL / min;

[0089] Elution method: isocratic elution;

[0090] Running time: 10 minutes;

[0091] Column temperature: 40℃;

[0092] Detector temperature: 45℃;

[0093] Injection volume: 20 μL.

[0094] Preparation of the test solution: Accurately weigh 1.0 g of the contents of Basic Example 1, place it in a 5 mL volumetric flask, add n-heptane to dissolve and dilute to the mark, shake well to obtain the test solution.

[0095] Preparation of reference solution: Accurately weigh / transfer the liquid paraffin shown in Table 2, place them in a 20mL volumetric flask, dissolve them in n-heptane and dilute to the mark, shake well to obtain the reference solution.

[0096] Table 2

[0097]

[0098] Accurately measure 10 μL of the test solution and reference solution and inject them into the liquid chromatograph. Record the chromatograms and determine the content of liquid paraffin using the standard curve method. The correlation coefficient between the peak area and concentration of other reference solutions of different concentrations should be greater than 0.995. The results are shown in Table 3.

[0099] Table 3

[0100]

[0101] The linearity requirement is a correlation coefficient r > 0.995 and an RSD < 10%. Therefore, the detection method of this invention meets the linearity requirement.

[0102] As can be seen from the basic examples 2-3, the choice of mobile phase has a great influence on the separation effect of liquid paraffin. Using n-heptane as the mobile phase can achieve a good separation effect of liquid paraffin, thereby realizing the effective detection of liquid paraffin in vitamin D drops. However, using methanol as the mobile phase cannot effectively separate liquid paraffin.

[0103] The contents of the vitamin D drops prepared in Basic Example 1 were used as a sample. The liquid paraffin content was tested under the analytical conditions of Basic Example 3. The liquid paraffin content in the vitamin D drops was found to be 0.67%, which does not meet the strictest FDA requirements (<0.2%).

[0104] Basic Example 4 uses medium-chain triglycerides to partially replace liquid paraffin oil as a lubricant in the production of vitamin D drops.

[0105] Based on the fact that the liquid paraffin content in Basic Example 1 exceeds FDA requirements, a solution is sought to partially replace liquid paraffin as a lubricant in the production of vitamin D drops. The specific process is as follows:

[0106] Except for the shot pressing process, the rest is the same as in basic Example 1.

[0107] The shot pressing process is as follows:

[0108] After installing and starting the capsule machine, connect the heat tracing cable and heating rod and preheat them. Set the glue tank temperature to 60℃, the glue storage box temperature to 60℃, the spray temperature to 40℃, and the cold air temperature to 18℃. After the set temperature is reached, compressed air is introduced into the glue tank to press out the glue liquid prepared in step (I). The switch of the oil tank containing liquid paraffin is opened to lubricate the rubber sheet. The main machine is turned on, the mold speed is set, the rubber sheet is pulled taut and placed in the track, and the thickness of the rubber sheet is adjusted. The conduit for introducing liquid paraffin on the shot press is disconnected at the connection of the pressure roller. The spray gun containing medium-chain triglycerides is used to fully spray the mold and pressure roller, lubricating the mold and pressure roller with the medium-chain triglycerides. The mold is tightened, the spray body is lowered, and the medicine liquid to be pressed prepared in step (II) is poured in. After the spray body temperature stabilizes, the spray body valve is opened, and the spray body temperature is adjusted to make the joint line flat and leak-proof. The loading amount is adjusted to 0.242g-0.258g. During pressing, the capsules pressed out when the spray body temperature fluctuation is > ±0.3℃ are discarded. The first pass rate of shot pressing is 95.7%.

[0109] The liquid paraffin content in the vitamin D drops prepared in Basic Example 4 was detected using the method of Basic Example 3. The liquid paraffin content in the vitamin D drops was found to be 0.50%, which is better than that of Basic Example 1, but still does not meet the most stringent FDA requirements (<0.2%). The chromatogram is shown below. Figure 1 .

[0110] Based on the fact that the liquid paraffin content in Basic Example 4 is higher than the FDA requirement, we are seeking a solution to use edible oil to completely replace liquid paraffin as a lubricant in the production of vitamin D drops, as detailed in Examples 1-7 and Comparative Example 1.

[0111] Example 1: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0112] Formulation (for production of 10,000 tablets)

[0113]

[0114]

[0115] Preparation process:

[0116] (I) Glue making

[0117] 1) Add the prescribed amount of glycerin and water to the gelling tank, turn on the stirrer, and set the temperature of the gelling tank to 75℃.

[0118] 2) When the temperature inside the gelatin dissolving tank reaches the set temperature, stop stirring, add the prescribed amount of gelatin, and then start stirring again. At the same time, evacuate to -0.05 to -0.06 MPa and maintain negative pressure stirring for 30 minutes.

[0119] 3) Adjust the set temperature of the gelling tank to 60℃, turn on the vacuum pump and evacuate for 45 minutes, stirring continuously during the evacuation process;

[0120] 4) Turn off the vacuum pump, stop stirring, open the atmospheric connection valve, keep at 60°C and let stand to degas. Let stand to obtain the adhesive solution.

[0121] (II) Solution Preparation

[0122] Add the prescribed amount of vitamin D to soybean oil and stir until well mixed at room temperature to obtain the medicine solution to be pressed.

[0123] (III) Shot Pressing

[0124] After installing and starting the capsule machine, connect the heating cable and heating rod and preheat them. Set the temperature of the glue tank to 60℃, the temperature of the glue storage box to 60℃, the temperature of the spray body to 40℃, and the temperature of the cold air to 18℃. After the temperature reaches the set temperature, introduce compressed air into the glue tank to press out the glue liquid prepared in step (I). Open the switch of the oil tank containing medium-chain triglycerides to lubricate the rubber. Turn on the main unit, set the mold speed, tighten the rubber and place it in the track, adjust the thickness of the rubber, press the mold, lower the spray body, and pour in the medicine liquid to be pressed prepared in step (II). After the spray body temperature stabilizes, open the spray body valve, adjust the spray body temperature to make the seam line flat and leak-proof, and adjust the filling amount to 0.242g-0.258g. Discard the capsules pressed when the spray body temperature fluctuation is > ±0.3℃ during pressing.

[0125] (iv) Shaping and drying

[0126] The pressed capsules are first shaped in a rotating drum for 20 minutes, and then dried overnight in a perforated tray.

[0127] Example 2: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0128] Except for step (iii), in which soybean oil is used to replace medium-chain triglycerides, the rest is the same as in Example 1.

[0129] Example 3: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0130] Except for replacing medium-chain triglycerides with olive oil in step (iii), the rest is the same as in Example 1.

[0131] Example 4: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0132] Except for step (iii), in which rapeseed oil is used to replace medium-chain triglycerides, the rest is the same as in Example 1.

[0133] Example 5: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0134] Except for replacing medium-chain triglycerides with peanut oil in step (iii), the rest is the same as in Example 1.

[0135] Example 6: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0136] Except for step (iii), in which medium-chain triglycerides and soybean oil are used as lubricants in a mass ratio of 1:1, the rest is the same as in Example 1.

[0137] Example 7: Preparation of Vitamin D Drops Using Edible Oil as a Lubricant

[0138] Except for step (iii), in which medium-chain triglycerides and soybean oil are used as lubricants in a mass ratio of 1:1.5, the rest is the same as in Example 1.

[0139] Comparative Example 1

[0140] Except for step (iii), in which coconut oil is used to replace medium-chain triglycerides, the rest is the same as in Example 1.

[0141] The liquid paraffin content and first-pass yield of the pelleting in Basic Examples 1 and 4, and the first-pass yield of the pelleting of Vitamin D drops prepared in Examples 1-7 and Comparative Example 1 are shown in Table 4.

[0142] Table 4

[0143]

[0144] As can be seen from Table 4, using different edible oils as lubricants in Examples 1-7 to produce vitamin D drops can avoid the presence of liquid paraffin in the vitamin D drops and achieve a shot-pressing pass rate that is comparable to or better than that of using liquid paraffin as a lubricant (Basic Example 1).

[0145] Comparing Examples 1-5 and Comparative Example 1, it can be seen that the type of edible oil also has a certain impact on the quality of pelleting. Due to differences in composition and surface tension, different edible oils have different effects on the lubrication of the pellets and the formation of the pellets. Soybean oil and medium-chain triglycerides showed the highest first-pass yield compared to other edible oils, while coconut oil had the lowest first-pass yield. Comparing Examples 1-2 and Examples 6-7, it can be seen that using a combination of soybean oil and medium-chain triglycerides can improve the first-pass yield of pelleting.

[0146] The present invention is not limited to the technical means disclosed above, but also includes technical solutions composed of any combination of the above technical features. The above descriptions are specific embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications are also considered within the scope of protection of the present invention.

Claims

1. Use of edible oil in the production of vitamin D drops, characterized in that, Vitamin D drops are produced using a soft capsule machine. In the capsule pressing process, edible oil is used as a lubricant to lubricate the capsule shell and complete the subsequent capsule pressing process. The edible oil is a mixture of medium-chain triglycerides and soybean oil in a mass ratio of 1:0.8-1.

5. The vitamin D drops include a contents and a gel; wherein the contents of the vitamin D drops are made from edible oil and vitamin D, and the gel of the vitamin D drops is made from gelatin, glycerin and purified water; the edible oil in the contents includes at least one of medium-chain triglycerides, olive oil, rapeseed oil, soybean oil and peanut oil, and the medium-chain triglycerides include at least one of medium-chain monoglycerides, medium-chain diglycerides and medium-chain triglycerides.

2. The application as described in claim 1, characterized in that, The density of the edible oil is 0.60-0.

95.

3. The application as described in claim 1, characterized in that, The edible oil is a mixture of medium-chain triglycerides and soybean oil, wherein the mass ratio of medium-chain triglycerides to soybean oil is 1:1.0-1.

5.

4. The application as described in claim 3, characterized in that, The edible oil is a mixture of medium-chain triglycerides and soybean oil, wherein the mass ratio of medium-chain triglycerides to soybean oil is 1:1.2-1.

5.

5. The application as described in claim 1, characterized in that, The specific process for producing vitamin D drops using a soft capsule machine is as follows: 1) Glue preparation: The raw materials for vitamin D drops are prepared into a glue solution in a glue preparation tank; 2) Solution preparation: Mix the raw materials of the vitamin D drops evenly to obtain the solution to be pressed; 3) Capsule pressing: The gelatinous liquid from step 1) and the liquid to be pressed from step 2) are pressed into wet capsules using a capsule machine; 4) Shaping and drying.

6. The application as described in claim 5, characterized in that, Step 3) The specific process of shot blasting is as follows: Set the temperature of the glue barrel to 50-70℃, the temperature of the glue storage box to 50-70℃, the temperature of the spray body to 35-45℃, and the temperature of the cold air to 16-20℃. After the temperature reaches the set temperature, introduce compressed air into the glue barrel to press out the glue liquid prepared in Step 1). Open the switch of the oil tank containing edible oil to lubricate the rubber, turn on the main unit, set the mold speed, tighten the rubber and put it into the track, adjust the thickness of the rubber, press the mold, lower the spray body, and pour in the pressurized medicine liquid prepared in Step 2). After the spray body temperature stabilizes, open the spray body valve, adjust the spray body temperature to make the joint line flat and leak-proof, and adjust the loading amount to 0.242g-0.258g.

7. The application as described in claim 5, characterized in that, The shot blasting process also includes a step of spraying edible oil onto the uneven areas of the rubber sheet to make the rubber sheet smoother and more easily wrap the contents.

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