CN115671056A

CN115671056A - Vitamin E granules and preparation method and application thereof

Info

Publication number: CN115671056A
Application number: CN202211263141.3A
Authority: CN
Inventors: 黄海琴; 朱红艳; 徐丽星
Original assignee: Nantong University
Current assignee: Nantong University
Priority date: 2022-10-14
Filing date: 2022-10-14
Publication date: 2023-02-03

Abstract

The invention discloses a vitamin E particle and a preparation method and application thereof. The vitamin E particles are prepared from vitamin E and a solid adsorption material; the solid adsorbent material may be selected from porous calcium silicate, colloidal silica or mica. The vitamin E particles have high drug loading capacity and good compressibility, and the vitamin E particles or vitamin E tablets which are attractive in appearance, proper in hardness, free of leakage and good in stability can be prepared.

Description

Vitamin E granules and preparation method and application thereof

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to vitamin E granules as well as a preparation method and application thereof.

Background

Vitamin E (Vitamin E ) is also called tocopherol, and its main component is alpha-tocopherol (molecular structure is shown as following formula), which is an important fat-soluble Vitamin in the body, can inhibit the free radical reaction in the body, and has multiple biological functions of resisting oxidation and regulating immunity. Vitamin E is insoluble in water, soluble in organic solvents such as ethanol, stable to heat, stable under acidic conditions, but very easy to oxidize. Vitamin E is clinically used for resisting oxidation, improving blood circulation, protecting tissues, reducing cholesterol, preventing hypertension and the like. When vitamin E is oxidized, the above-mentioned biological activity is significantly reduced. Therefore, how to prepare liquid vitamin E to solidify and maintain its stability is a difficult problem in clinical application.

Vitamin E products in the market at present comprise vitamin E tablets, vitamin E injections and vitamin E soft capsules, wherein the most common vitamin E product is a soft capsule preparation. At present, the soft capsule has wide application fields in the fields of medicines, foods and cosmetics, and has become a preferred preparation form of a part of hydrophobic drugs, low-melting-point drugs, easily-oxidized drugs and various oily solution solidification due to the advantages of high bioavailability, safe sealing, accurate content and the like of the soft capsule. However, soft capsules also have inevitable drawbacks during application. The capsule shell of soft capsules is usually made of gelatin, and the aging and hardening of the gelatin, which are caused by long-term storage, moisture content, temperature, ultraviolet light and irradiation of visible light, lead to slow disintegration of the soft capsule. Because the capsule shell contains more glycerin, the phenomenon of adhesion is easy to occur in the storage process or at higher temperature. The soft capsule has complex production and preparation process, high requirements on instruments, temperature, humidity and the like in the preparation process, and the defects of easy oil leakage, high glue solution viscosity and the like in the preparation process, thereby increasing the difficulty of the production of the soft capsule. In addition, emulsifiers, preservatives, fatty substances and the like are usually added into the soft capsule, so that the soft capsule has the risk of poor stability and the like.

In view of these drawbacks of soft gelatin capsules, attempts have been made in the prior art to non-softgel vitamin E by microencapsulation or embedding techniques. However, the embedding technology or the microencapsulation technology has the defects of low encapsulation efficiency, easy oil leakage, poor stability, complex preparation process and the like.

Disclosure of Invention

The invention aims to overcome the existing defects of a vitamin E soft capsule carrier and provide a vitamin E granule with simple preparation method and high stability.

In order to achieve the purpose, the invention adopts the following technical scheme:

a vitamin E granule is prepared from vitamin E and solid adsorbent material; the solid adsorbent material is selected from porous calcium silicate, colloidal silica or mica.

Further, the solid adsorption material is porous calcium silicate.

Furthermore, the dosage of the vitamin E and the porous calcium silicate is 3.0-5.0L: 1g of the total weight of the composition. Preferably 4.0 to 5.0L:1g of the total weight of the composition.

The preparation method of the vitamin E granules comprises the steps of adding the solid adsorption material and the vitamin E into a high-speed stirring granulator, and continuously stirring the solid adsorption material and the vitamin E at the rotating speed of 200-500 rpm to fully and uniformly mix the solid adsorption material and the vitamin E, so that the vitamin E granules are obtained.

Further, the rotation speed is preferably 300 to 400rpm.

Mixing the obtained vitamin E granules with lubricants such as magnesium stearate or talcum powder, and directly tabletting; alternatively, the obtained vitamin E granules are mixed with a direct compression excipient (e.g., MCC PH-302, lactose FlowLac 100, etc.) uniformly, and then magnesium stearate or talc powder is added to the mixture, and the mixture is mixed uniformly and then tabletted.

The vitamin E particles have high drug loading capacity and good compressibility, and the vitamin E particles or vitamin E tablets which are attractive in appearance, proper in hardness, free of leakage and good in stability can be prepared.

Drawings

FIG. 1 is a scanning electron micrograph of calcium silicate (A) and vitamin E granules (B) in example 1.

Fig. 2 shows the results of the determination of the angle of repose of different drug-loaded particles in example 1.

Detailed Description

The invention is described in further detail below with reference to the figures and the specific examples, which should not be construed as limiting the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention. The experimental methods and reagents of the formulations not specified in the examples were carried out according to the conventional conditions in the art.

Example 1

Examination of the liquid absorption capacity of different absorbent materials. Oily liquid vitamin E is slowly dripped into materials such as porous calcium silicate, colloidal silicon dioxide, microcrystalline cellulose, mica, talcum powder and the like, and the oil absorption capacity of different materials with the same quantity on liquid is recorded.

Table 1 investigation of liquid oil absorption properties of different adsorption materials

As shown in Table 1, the oil absorption of the porous calcium silicate is the largest, the oil absorption value reaches 4.4mL/g, and the particles are drier and have good fluidity. The results show that the porous calcium silicate has a high oil absorption value.

As shown in fig. 1, the porous calcium silicate is rich in pores, and oil droplets are uniformly adsorbed on the surface of the porous calcium silicate after the oily carrier is added, which shows that the porous calcium silicate of the type has good capacity of adsorbing oily drugs.

Meanwhile, the flowability of the particles after adsorbing the oily drug with porous calcium silicate, colloidal silicon dioxide and microcrystalline cellulose as carriers was measured. As a result, as shown in fig. 2, the porous calcium silicate particles had an angle of repose of 42 ° and had good fluidity.

Example 2

100g of solid adsorbing material and 100g of vitamin E are fully mixed to obtain 1:1 vitamin E granules. Wherein, the solid adsorption material is colloidal silicon dioxide and porous calcium silicate respectively.

Separately, 50g of vitamin E granules were put into a polyethylene bag, sealed, placed in a drug stability test box at 40 ℃/75% RH, and the change in the vitamin E content was measured under relatively severe storage conditions to evaluate the stability.

Table 2 determination of vitamin E particle content

Reaction conditions (40 ℃,75% RH)	Porous calcium silicate	Colloidal silica
			Day
0	99.45％	99.21％
			Day 5	99.20％	98.62％
Day 10	99.04％	98.1％
			Day 15	98.37％	94.26％
Day 30	97.47％	90.21％

The results show that vitamin E granules prepared with colloidal silica as the solid adsorption material had a significantly reduced content at 40 ℃ under a relative humidity of 75% RH; and the porous calcium silicate is used as a solid adsorbent, although no antioxidant exists, the content of the vitamin E particles is reduced by less than 1 percent within 15 days of placement, and the stability is higher within 30 days.

Example 3

The vitamin E granules prepared in example 2 were added with an appropriate amount of talc powder and directly tableted. The tablet appearance (color, whether oil stain exists, whether the tablet is cracked or not, whether oil leakage exists or not) and the tablet hardness are used as indexes to examine the tabletting effect.

Table 3 compressibility examination of vitamin E particles

	Colloidal silica	Porous calcium silicate
			Hardness of	20N	80N
Appearance of the product	With oil stain	White (slight yellow)
			Breakage rate	60％	Almost without breakage
Whether or not there is a leak	More leakage	Leakage of fluid

As shown in table 3. During the tabletting process, it is possible that the crystalline structure of the porous calcium silicate is broken at a relatively low pressure, so that the structures are tightly bonded together, showing superior bonding ability, and achieving the desired hardness with a minimum of pressure. At the same time, strong adhesive properties can be exhibited at low pressure.

The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments, and improvements and modifications without departing from the scope of the present invention should be within the scope of the present invention.

Claims

1. A vitamin E granule characterized by: is prepared from vitamin E and solid adsorption material; the solid adsorbent material is selected from porous calcium silicate, colloidal silica or mica.

2. Vitamin E granules according to claim 1, characterized in that: the solid adsorption material is porous calcium silicate.

3. Vitamin E granules according to claim 3, characterized in that: the dosage of the vitamin E and the porous calcium silicate is 3.0 to 5.0L:1g of the total weight of the composition.

4. A process for the preparation of vitamin E granules according to claim 1, characterized in that: adding the solid adsorption material and the vitamin E into a high-speed stirring granulator, and continuously stirring the solid adsorption material and the vitamin E at the rotating speed of 200-500rpm to fully mix the solid adsorption material and the vitamin E to obtain vitamin E granules.

5. The method of claim 4, wherein: the rotation speed is preferably 300 to 400rpm.

6. Use of vitamin E granules according to any one of claims 1 to 3 for the preparation of a vitamin E preparation.

7. Use according to claim 6, characterized in that: the vitamin E preparation is obtained by mixing vitamin E granules with a direct compression excipient and then tabletting.