CN102670563A - Preparation method of soft capsule without gelatin - Google Patents

Abstract

The invention discloses a method for preparing gelatin-free soft capsules, which belongs to the technical field of soft capsule processing. The present invention uses pullulan polysaccharide as the main ingredient, mixes it with microbial polysaccharide gums such as xanthan gum, carrageenan or gellan gum or seaweed polysaccharide gum respectively, and makes a rubber film through processes such as sol, degassing, salivation, and drying, and then It is made by pressing with a rotary film method soft capsule machine. The present invention only uses pullulan, xanthan gum, carrageenan and other microbial polysaccharide gums or seaweed gums as raw materials, does not use gelatin at all, and adopts the two-step process of "salivating film making" and "rotating film soft capsule pressing". During the pressing process, any oil-soluble medicine or health food can be loaded to obtain gelatin-free soft capsules.

Description

A kind of preparation method of gelatin-free soft capsule

technical field

The invention discloses a method for preparing gelatin-free soft capsules, which belongs to the technical field of soft capsule processing.

Background technique

Soft capsules refer to capsules in which medicinal material extracts, liquid medicines or appropriate excipients are mixed evenly and then sealed in soft capsules by dripping or pressing methods. They are prepared by dripping or pressing methods, and their shapes are round, Oval shape, fish shape, tube shape etc. According to statistics, in the current new drug development process, more than 40% of the new chemical systems exhibit poor biopharmaceutical properties, such as low solubility or poor permeability. These deficiencies pose a serious challenge to the development of orally absorbable compounds and oral formulations. The development of soft capsule preparations has made up for the poor water solubility of some oral compounds to a certain extent. Compared with other oral preparations, soft capsule preparations can not only provide a liquid medium to make the drug easy to dissolve, but also improve the biopharmaceutical efficacy of hydrophobic compounds, and minimize the amount of dust in the drug production process. This improves the safety of production personnel. In addition, soft capsules are not only used in medicine, but also widely used in cosmetics, bathroom supplies, nutritional health products, art supplies, etc.

Soft capsules have elasticity and plasticity, can prevent oxidation, moisture and light, and can improve drug stability. Since there is no binder, the material is not pressed during the preparation process, so the drug release is fast and the bioavailability is good. The content uniformity is good, and the content deviation is very low.

Soft capsules are suitable as the carrier of the following drugs:

1. Oily substances and low melting point substances are most suitable for making soft capsules. the

2. Substances that are unstable when exposed to light, humidity and heat, and easily oxidized can be made into soft capsules.

3. Soft capsules can be made into rectal suppositories.

4. Drugs with bad smell and soft capsules of trace active drugs. the

5. Drugs with volatile components and easy to escape. the

6. Hydrophobic drugs with poor bioavailability.

At present, the soft capsules sold in my country's market are mainly gelatin soft capsules prepared by pressing. The medicinal solution is placed on a film of uniform thickness made of gelatin-based soft capsule material, and pressed through a mold. The shape of the mold determines the shape of the capsule. There are two types of pressing methods, the flat film method and the rotating film method, and the rotating film method is the current mainstream method. During the production of the pressing method, two tapes are made from the tape shaping drum, and are transferred to the left and right rotary dies through the upstream rollers, and the tapes are squeezed and bonded through the die hole flanges of the left and right rotary dies, and the wedge-shaped liquid injector is simultaneously extruded in the die holes. A certain amount of material liquid (medicine or health food, etc.) is injected into the pressed cavity. Due to the continuous rotation of the rolling die, the flange of the die hole squeezes and bonds the adhesive tape to form a soft capsule.

However, the basic components of currently commercially available gelatin soft capsules include gelatin, glycerin and water. Gelatin is a kind of protein substance obtained by hydrolysis of animal skin and bone. Since the gelatin rubber is easy to lose water and become hard, absorb water and become soft, and will undergo cross-linking reaction when it encounters aldehydes, it is not suitable to use substances that are easy to absorb moisture, weather and chemically react with the capsule shell for filling. In addition, because the hydrophilic substances in the content will migrate to the gelatin shell, which limits its wide application, especially in traditional Chinese medicine. The "mad cow disease" that swept across Europe in recent years also had an impact on the traditional capsule market. The US FDA believes that gelatin should be removed from the list of routinely safe foods. In addition, Buddhists, Muslims and vegetarians will not accept this kind of animal gelatin soft capsules. In China, the quality inspection of soft capsules only focuses on the contents, and does not regulate the quality standards of soft capsule shells. For a long time, there have been some deficiencies in the quality inspection of soft capsule shells, coupled with the lack of management in the domestic gelatin market, the quality is uneven, and some people even use industrial gelatin prepared from leather base rubber to prepare soft capsules, making traditional gelatin soft capsules There are many potential safety hazards in quality.

Therefore, in order to meet the needs of the market, it is particularly important to develop soft capsules that do not contain gelatin ingredients. At present, some natural, semi-synthetic and synthetic substances have been used to replace gelatin to prepare the capsule skin of soft capsules. Such as gum arabic, xanthan gum, ethyl cellulose (EC), carboxy methyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), etc.

The invention uses pullulan polysaccharide as the main material and combines it with other compound glues to successfully develop a new polysaccharide-based soft capsule without gelatin, which can be used for filling oil-soluble medicines and health foods.

Contents of the invention

The purpose of the present invention is to provide a preparation method of gelatin-free soft capsules, and make a gelatin-free polysaccharide-based soft capsule product.

Technical scheme of the present invention: a preparation method of gelatin-free soft capsules, using pullulan polysaccharide as the main ingredient, mixed with microbial polysaccharides: xanthan gum, carrageenan or gellan gum, or seaweed polysaccharide gum as compound ingredients, After sol, degassing, salivation, drying and other processes to make a rubber film, and then use the rotary film method soft capsule machine to compress. Gelatin is not used at all, and the two-step process of "salivating film making" and "rotating film soft capsule pressing" is adopted. During the pressing process, any oil-soluble medicine or health food that needs to be filled is packed into the soft capsule, that is, Gelatin-free soft capsules are available. The steps are:

(1) Sol and salivation film production:

Weigh 100g of pullulan, add 2~8g of one or several microbial polysaccharide gums or alginate (such as xanthan gum, carrageenan, or gellan gum, etc.) and mix. Add 500~1000mL of deionized water and 40~90g of glycerin, place in a constant temperature water bath at 70-80°C to heat and stir to dissolve, after 3 hours of dissolution, place the completely dissolved glue in a vacuum of 0.09~0.1Mpa Degassing at low temperature for 30 minutes, pour the degassed glue into the film forming device, dry at 60~70°C for 10~18 hours, and peel off the film after it is completely dry.

(2) Compression of gelatin-free soft capsules:

Two gelatin-free diaphragms made by the above-mentioned process are respectively placed on the two rollers of the rotary film method soft capsule pressing machine, then soft capsule molding is carried out according to the conventional gelatin soft capsule pressing process, and the obtained gelatin capsules are formed while molding. Medicines or health food that need to be filled are packed into soft capsules.

Beneficial effects of the present invention:

This product uses polysaccharide mixture as the film-forming material of soft capsules, without using any gelatin ingredients, and the product is safe and reliable. The samples have passed the mechanical performance test and disintegration test of soft capsules, and all performance indicators have reached the technical standards of gelatin soft capsules.

The present invention can completely change the current situation that gelatin is used as the main film-forming material in my country's soft capsules, improve the scientific and technological level of my country's soft capsule processing industry, greatly improve the economic benefits of enterprises, and provide a new method for my country's pharmaceutical enterprises and health food production enterprises. A new dosage form to protect people's health.

Detailed ways

Example 1

Weigh 100g of pullulan and 3g of xanthan gum, mix them evenly, add 50g of glycerin, then add 500mL of deionized water, mix them evenly, place them in a constant temperature water bath at 70°C for heating and stirring to dissolve, place them in a 0.09~0.1Mpa Degassing under vacuum for 30 minutes, then poured into a film forming device, dried in a drying oven at 60-70°C for 12 hours, and peeled off the film. Two gelatin-free diaphragms made by the above-mentioned process are respectively placed on the two rollers of the rotary film method soft capsule pressing machine, then soft capsule molding is carried out according to the conventional gelatin soft capsule pressing process, and the obtained gelatin capsules are formed while molding. Medicines or health food that need to be filled are packed into soft capsules. The prepared soft capsules are similar to gelatin soft capsules in terms of transparency, elasticity and mechanical strength, and the disintegration time limit meets the standard stipulated in the 2005 edition of the National Pharmacopoeia for soft capsules, and they are completely dissolved within 15 minutes.

Example 2

Weigh 100g of pullulan and 4g of carrageenan, mix well, add 60g of glycerin, then add 700mL of deionized water, mix well, heat and stir in a constant temperature water bath at 70°C to dissolve, and place in a vacuum of 0.09~0.1Mpa Degassing at high temperature for 30 minutes, then poured into the film forming device, dried in a drying oven at 60~70°C for 14 hours, and peeled off the film. Put two gelatin-free diaphragms prepared by the above-mentioned process on the two rollers of the rotary film method soft capsule manufacturing machine, then carry out soft capsule molding according to the pressing process of conventional gelatin soft capsules, and place the gelatin capsules at the same time as molding. The medicine that needs to be filled is put into the soft capsule. The prepared soft capsules are similar to gelatin soft capsules in terms of transparency, elasticity and mechanical strength, and the disintegration time limit meets the standard stipulated in the 2005 edition of the National Pharmacopoeia for soft capsules, and they are completely dissolved within 15 minutes.

Example 3

Weigh 100g of pullulan polysaccharide and 2g of gellan gum, mix well, add 70g of glycerin, then add 900mL of deionized water, mix well, place in a constant temperature water bath at 70°C to heat and stir to dissolve, place in a 0.09~0.1Mpa Degassing under vacuum for 30 minutes, then poured into a film forming device, dried in a drying oven at 60~70°C for 18 hours, and peeled off the film. Put two gelatin-free diaphragms prepared by the above-mentioned process on the two rollers of the rotary film method soft capsule manufacturing machine, then carry out soft capsule molding according to the pressing process of conventional gelatin soft capsules, and place the gelatin capsules at the same time as molding. The medicine that needs to be filled is put into the soft capsule. The prepared soft capsules are similar to gelatin soft capsules in terms of transparency, elasticity and mechanical strength, and the disintegration time limit meets the standard stipulated in the 2005 edition of the National Pharmacopoeia for soft capsules, and they are completely dissolved within 15 minutes.

Claims (4)

1. gelatin-free preparation of soft capsule method; It is characterized in that with the pulullan polysaccharide being major ingredient, be equipped with microbial polysaccharide: xanthan gum, carrageenan or gellan gum, or alginate jelly is composite material; Do not use gelatin fully; Adopt " sialorrhea system film " and " rotating the compacting of embrane method soft capsule " two step process, in pressing process, any oil-soluble medicine of required fill or health food are packed in the soft capsule, make the soft capsule that does not contain gelatin; Step is:

(1) colloidal sol and sialorrhea system film:

Take by weighing pulullan polysaccharide 100g; Add a kind of or several microorganisms polysaccharide glue or alginate jelly 2 ~ 8g, mix, add deionized water and the 40 ~ 90g glycerol of 500 ~ 1000mL; The heated and stirred dissolving; Glue after the dissolving fully placed carry out deaeration under the vacuum, the glue after the deaeration is poured in the film formation device, treat to take off film behind its bone dry;

(2) compacting of gelatin-free soft capsule:

Two gelatin-free diaphragms that (1) prepared is good set by step are placed on respectively on two rollers of rotation embrane method soft capsule press; Pressing process according to the normal gelatin soft capsule carries out the soft capsule molding then, and in molding, the medicine of required fill or health food is packed in the soft capsule.

2. according to the said gelatin-free preparation of soft capsule of claim 1 method, it is characterized in that heated and stirred is dissolved as described in the step (1): 70 ~ 80 ℃ of heated and stirred are dissolved 3 h.

3. according to the said gelatin-free preparation of soft capsule of claim 1 method, it is characterized in that glue described in the step (1) places carries out deaeration and be under the vacuum: glue places under the vacuum of 0.09 ~ 0.1Mpa and carries out deaeration 30min.

4. according to the said gelatin-free preparation of soft capsule of claim 1 method, it is characterized in that treating described in the step (1) that taking off film behind its bone dry is: place 60 ~ 70 ℃ of down dry 10 ~ 18h, treat to take off film behind its bone dry.