Vitamin d2 microcapsules and methods of making the same

Abstract

The application belongs to the technical field of medicine embedding, and particularly discloses a vitamin D2 microcapsule and a preparation method thereof, which comprises a coating layer and a core layer in the coating layer, wherein the coating layer is a high molecular film coating material, and comprises acrylic resin L100 and a styrene maleic acid copolymer; the core layer is vitamin D2; and the mass ratio of the coating layer to the core layer is 1:20-50.The specific preparation steps are as follows: S1, dispersing vitamin D2 in an organic solvent under a protective atmosphere; S2, dissolving the high molecular film coating material with an organic solvent; S3, dropping the solution obtained in S2 into the solution obtained in S1, uniformly mixing, and removing the organic solvent through evaporation to obtain the vitamin D2 microcapsule.The vitamin D2 microcapsule provided by the application has good stability in the raw drug stage after being prepared by the above method, and has the characteristics of simple process route, good coating effect, high drug bioavailability and the like, and is convenient for engineering application.

Description

Technical Field

[0001] This invention belongs to the field of drug encapsulation technology, specifically relating to vitamin D2 microcapsules and their preparation methods. Background Technology

[0002] Vitamin D2 (VD2) is a vitamin used to prevent and treat rickets and osteomalacia. It is insoluble in water but readily soluble in ether and ethanol. It is easily degraded by light, oxygen, and heat; therefore, improving the stability of VD2 is an important research direction for this type of material.

[0003] Currently, the main technical solutions focus on microencapsulation technology. This technology encapsulates solids, liquids, or gases within microcapsules to form semi-permeable or sealed membranes, and allows for control over the release rate of the core material. The encapsulated substance is generally called the core material, and the encapsulating material is called the wall material. The particle size is approximately 1–1000 μm, and the shapes include square, spherical, rice-grain-shaped, or irregular. The capsule wall has a single-layer or multi-layer structure and can contain one or more core materials. The advantages of microencapsulation technology are: 1. It can improve some physical properties of the encapsulated substance (solubility, apparent density, appearance, color, etc.), reduce the impact of the environment on the encapsulated substance, thereby improving the stability of the encapsulated substance; 2. It allows for controlled release of substances as needed; reduces the toxicity of substances; and isolates incompatible substances; 3. It can mask tastes and odors, etc.

[0004] Peng Xianghong et al., in their paper "Stability and Structural Study of Vitamin D2 Encapsulated by β-Cyclodextrin" published in the Journal of Wuhan University, used β-cyclodextrin to form an inclusion complex with vitamin D2 (VD2) in a 60% ethanol aqueous solution. They measured the change in VD2 content in the inclusion complex under accelerated experimental conditions of light, high temperature, and high humidity. The results showed that the inclusion complex formed intermolecular hydrogen bonds and a new crystal form, thereby improving its stability. However, this process uses a phase separation encapsulation technique, but the amount of β-cyclodextrin used as the wall material is several times that of the VD2 used as the core material. The introduction of a large amount of wall material will seriously affect the dosage accuracy of subsequent formulations.

[0005] CN110368369A, "Calcium Supplements and Their Preparation Methods," discloses a calcium supplement and its preparation method. Through the physical blending and synergistic effect of calcium salts, vitamin D, and various functional excipients, sustained-release and immediate-release tablet cores are prepared. This controls the rational release of the effective components of the calcium supplement and vitamin D in the gastrointestinal tract after oral administration, thereby promoting effective calcium intake and improving the total calcium absorption rate. The inventors found that this patent application focuses on improving the effect of vitamin D in the finished drug from a macroscopic level, failing to delve into the microscopic level to protect vitamin D from oxidative deterioration during storage.

[0006] CN114209065A, "A Vitamin D2 Microcapsule Powder and Its Preparation Method," discloses a method for preparing vitamin D2 microcapsules. The method involves dissolving vitamin D2 microcapsules in vegetable oil, emulsifying them with modified starch and antioxidants, spray drying, and encapsulating them with starch to form the microcapsule product. The product's characteristics include high stability and water solubility due to the emulsification process forming microcapsules.

[0007] Due to its inherent properties, it can be added to milk powder, rice cereal, soft drinks, and calcium supplements to supplement vitamin D2. However, this invention is applied in the food industry, which differs significantly from the application scenarios of pharmaceutical raw materials, and therefore cannot meet the vitamin D2 testing requirements for pharmaceutical raw materials. Summary of the Invention

[0008] This invention provides a vitamin D2 microcapsule and its preparation method. This method can easily form a good molecular thin film layer on the surface of vitamin D2 powder, which can isolate the influence of external factors and better protect the stability of vitamin D2 powder in the raw material stage.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: a vitamin D2 microcapsule, the microcapsule comprising a coating layer and an inner core layer, wherein the coating layer is a polymer film coating material, including acrylic resin L100 and styrene-maleic acid copolymer; the core layer is vitamin D2; the mass ratio of the coating layer to the core layer is 1:20~50.

[0010] Furthermore, the microcapsule particle size is 20-50 μm.

[0011] Furthermore, the mass ratio of acrylic resin L100 to styrene-maleic acid copolymer is 5:1~3.

[0012] Furthermore, the mass ratio of acrylic resin L100 to styrene-maleic acid copolymer is 5:2.

[0013] This invention also relates to a method for preparing the aforementioned vitamin D2 microcapsules, comprising the following steps:

[0014] S1. Disperse vitamin D2 in an organic solvent under a protective atmosphere;

[0015] S2. Dissolve the polymer film coating material in an organic solvent;

[0016] S3. Add the solution obtained in S2 dropwise to the solution obtained in S1, mix well, and then remove the organic solvent by evaporation to obtain vitamin D2 microcapsules.

[0017] Furthermore, the organic solvent in S1 is one or a mixture of several of diethyl ether, ethanol, and methanol.

[0018] Furthermore, the mass ratio of vitamin D2 to organic solvent is 1:5~10.

[0019] Furthermore, the organic solvent in S2 is one or a mixture of acetone, ethanol, and isopropanol; the mass ratio of the polymer film coating material to the organic solvent is 1:3~10.

[0020] Furthermore, the mass ratio of the polymer film coating material to the organic solvent is 1:5~7.

[0021] Furthermore, when removing organic solvents by evaporation, a rotary evaporator is used for vacuum distillation at a temperature below 35°C. After the vacuum level reaches below -0.095 MPa, it is maintained for 10 to 15 minutes. Then, the inlet valve is opened, the material is poured out, and it is allowed to cool naturally to room temperature.

[0022] The present invention has the following beneficial effects:

[0023] This invention uses a polymeric film coating material made of acrylic resin L100 and styrene-maleic acid copolymer as the coating layer. Acrylic resin L100 is relatively stable in acidic media and does not release in gastric acid; however, in alkaline media, it reacts with alkali to form soluble salts, rapidly releasing vitamin D2, thus allowing for precise delivery to absorption sites such as the small intestine. The combination of acrylic resin L100 and styrene-maleic acid copolymer enhances the hydrogen bonding between the resin and vitamin D2 molecules, strengthens the bonding effect between the coating layer and the vitamin D2 surface, significantly improves the stability of the active pharmaceutical ingredient vitamin D2, and extends its shelf life. Detailed Implementation

[0024] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention.

[0025] Example 1

[0026] The method for preparing vitamin D2 microcapsules includes the following steps:

[0027] (1) Preparation of dispersion: Under nitrogen protection, weigh 100g of vitamin D2 (VD2) and disperse it in 1000g of methanol solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0028] (2) Preparation of coating solution: Accurately weigh 4.0g of acrylic resin L100 and 1g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 25g of propanol and isopropanol, and set aside for use;

[0029] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 32℃. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0030] Example 2

[0031] The method for preparing vitamin D2 microcapsules includes the following steps:

[0032] (1) Preparation of dispersion: Under nitrogen protection, weigh 5g of vitamin D2 (VD2) and disperse it in 25g of methanol solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0033] (2) Preparation of coating solution: Accurately weigh 0.07g of acrylic resin L100 and 0.03g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 0.7g of equal amounts of propanol and isopropanol, and set aside for later use;

[0034] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 34℃. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0035] Example 3

[0036] The method for preparing vitamin D2 microcapsules includes the following steps:

[0037] (1) Preparation of dispersion: Under nitrogen protection, weigh 500g of vitamin D2 (VD2) and disperse it in 2500g of ether solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0038] (2) Preparation of coating solution: Accurately weigh 10g of acrylic resin L100 and 6g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 84g of propanol and isopropanol, and set aside for use;

[0039] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 30℃. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0040] Example 3

[0041] The method for preparing vitamin D2 microcapsules includes the following steps:

[0042] (1) Preparation of dispersion: Under nitrogen protection, weigh 2000g of vitamin D2 (VD2) and disperse it in 10000g of ethanol solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0043] (2) Preparation of coating solution: Accurately weigh 30g of acrylic resin L100 and 10g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 280g of propanol and isopropanol, and set aside for use;

[0044] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 35°C. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0045] Example 4

[0046] The method for preparing vitamin D2 microcapsules includes the following steps:

[0047] (1) Preparation of dispersion: Under nitrogen protection, weigh 50g of vitamin D2 (VD2) and disperse it in 300g of ethanol solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0048] (2) Preparation of coating solution: Accurately weigh 1.5g of acrylic resin L100 and 0.6g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 12.6g of propanol and isopropanol, and set aside for use;

[0049] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 35°C. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0050] Example 5

[0051] The method for preparing vitamin D2 microcapsules includes the following steps:

[0052] (1) Preparation of dispersion: Under nitrogen protection, weigh 300g of vitamin D2 (VD2) and disperse it in 1500g of methanol solution. Stir at room temperature until VD2 is fully dispersed and set aside for use.

[0053] (2) Preparation of coating solution: Accurately weigh 5.0g of acrylic resin L100 and 1.0g of styrene-maleic acid copolymer, dissolve them in a mixed solvent of 30.0g of propanol and isopropanol, and set aside for use;

[0054] (3) Coating treatment: The coating liquid is slowly added to the dispersion, stirred evenly and then poured into the rotary evaporator bottle. The temperature is set to 35°C. The organic solvent is removed by ultrasonic vibration and rotary evaporation. After the vacuum degree reaches below -0.095MPa, the air inlet valve is slowly opened after 10 minutes, the material is poured out and cooled naturally to room temperature to obtain vitamin D2 microcapsules.

[0055] The vitamin D2 microcapsules obtained in the above examples were placed in open petri dishes at room temperature for 1 to 6 weeks. The vitamin D2 content was determined according to CN115184519 A "Detection Method for Vitamin D Dissolution in Vitamin D Soft Capsules", with unencapsulated vitamin D2 as a control; see Table 1 for details.

[0056] Table 1

[0057] .

[0058] As shown in Table 1, the stability of vitamin D2 was improved to varying degrees through microencapsulation, with the vitamin D2 content increasing by 75.8%-139.9% compared to unencapsulated vitamin D2. In Example 4, the vitamin D2 content remained above 80% even after six weeks.

[0059] The above embodiments describe preferred embodiments of the present invention, but the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other way. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention. Therefore, the protection scope of this patent should be determined by the appended claims.

Claims

1. A vitamin D2 microcapsule for improving vitamin D2 stability, characterized in that: The vitamin D2 microcapsule comprises a polymer film coating material covering layer and an inner vitamin D2 core layer; the polymer film coating material comprises acrylic resin L100 and styrene-maleic acid copolymer, with a mass ratio of 5:1~3; the mass ratio of the coating layer to the core layer is 1:20~50; The specific steps for preparing vitamin D2 microcapsules are as follows: S1. Disperse vitamin D2 in an organic solvent under a protective atmosphere; the organic solvent in this step is one or a mixture of several of diethyl ether, ethanol, and methanol. S2. Dissolve the polymer film coating material in an organic solvent; the organic solvent in this step is one or a mixture of acetone, ethanol, and isopropanol; the mass ratio of the polymer film coating material to the organic solvent is 1:3~10. S3. Add the solution obtained in S2 dropwise to the solution obtained in S1, mix well, and then remove the organic solvent by evaporation to obtain vitamin D2 microcapsules.

2. The vitamin D2 microcapsule according to claim 1, characterized in that: The microcapsule particle size is 20-50 μm.

3. The vitamin D2 microcapsule according to claim 1, characterized in that: The mass ratio of acrylic resin L100 to styrene-maleic acid copolymer is 5:

2.

4. The vitamin D2 microcapsule according to claim 1, characterized in that: The mass ratio of vitamin D2 to organic solvent in S1 is 1:2~5.

5. The vitamin D2 microcapsule according to claim 1, characterized in that: The mass ratio of polymer film coating material to organic solvent in S2 is 1:5~7.

6. The vitamin D2 microcapsules according to any one of claims 1 to 5, characterized in that: When removing organic solvents by evaporation in S3, a rotary evaporator is used for vacuum distillation at a temperature below 35°C. After the vacuum reaches below -0.095MPa, it is maintained for 10-15 minutes. Then, the inlet valve is opened, the material is poured out, and it is allowed to cool naturally to room temperature.