CN108498478A - A kind of preparation method of starch base hard capsule - Google Patents

Abstract

The invention belongs to technical field of medicine preparation, specifically disclose a kind of preparation method of starch base hard capsule.The preparation method includes starch acidolysis, etherificate, colloidal sol, heat preservation, defoams, dips in gum forming, drying and other steps.The present invention is using acidolysis and is etherified composite modified processing starch, reduces the viscosity of starch, while improving the filming performance of starch；It for 80% high amylose starches is matrix to use amylose content, and modified starch is reinforced phase, and the technique for passing through traditional dip mold prepares starch base hard capsule.Not only have many advantages, such as that transparency is high by the starch base hard capsule prepared by the method for the present invention, show that smooth, folding resistance is good, disintegration time limited is short, also simplifies production technology, be suitble to large-scale promotion application.

Description

A kind of preparation method of starch-based hard capsule

technical field

The invention relates to the technical field of medicine preparation, in particular to a method for preparing starch-based hard capsules.

Background technique

Capsules are generally used to package drugs that are not suitable for direct contact with the esophagus and need to be disintegrated in the stomach or intestinal tract. At present, most of the hard capsules of medicinal or health food are made of gelatin, and gelatin still has certain problems in terms of medicinal properties and safety. On the one hand, gelatin comes from animal skin or bone, which is treated with acid or alkali and boiled. In the production process, there will inevitably be animal protein residues, which are prone to cross-linking reactions with the drugs contained in them and have the risk of carrying viruses, which will lead to adverse consequences such as drug deterioration. On the other hand, animal-derived gelatin is unacceptable to vegetarians and those who hold Islamic, Jewish and other religious beliefs. In addition, people with allergies should also avoid taking gelatin products. Therefore, it is extremely important to find substitutes for gelatin capsules.

Starch is a plant source with a wide range of sources and a very low price. It has good film-forming properties. It is very attractive to prepare empty capsules with it. However, because starch molecules are easy to form strong hydrogen bonds, the starch film is fragile. Brittle, it is difficult to make hollow capsules with high strength and filling resistance. In the existing process of preparing starch hard capsules by traditional dipping and forming methods, the biggest difficulty is that the viscosity of the starch solution is too high and it is difficult to control the thickness. Therefore, finding suitable modified starch materials, and studying the rheology and film-forming properties of starch materials and the phase change of starch during processing to meet the requirements of traditional gelatin equipment and technology is one of the problems that need to be solved urgently.

Contents of the invention

The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art, and provide a method for preparing starch-based hard capsules, which uses acid hydrolysis and etherification compound modification to treat the starch, reduces the viscosity of the starch, and improves the film-forming performance of the starch; Using high amylose starch with 80% amylose content as matrix and modified starch as reinforcing phase, starch-based hard capsules were prepared by traditional dipping and forming process.

Another object of the present invention is to provide the application of the starch-based hard capsules prepared by the above method in the preparation of medicines, health products and functional foods.

In order to achieve the above object, the present invention is achieved through the following schemes:

A preparation method for starch-based hard capsules, comprising the steps of:

S1. Take an appropriate amount of starch and use a hydrochloric acid solution with a concentration of 0.14mol/L to prepare the starch into starch milk with a starch content of 40%, and place it at 35-40°C and 200rpm for 6-24 hours; then use a mass fraction of 5% Adjust the pH of the starch milk to 5.5 with NaOH solution; discard the supernatant after centrifugation, add twice the volume of water to wash by centrifugation for 3 times, dry and react at 40-45°C for 10-12 hours to obtain acid-thinned starch;

S2. Take the acid-thinned starch obtained in S1, prepare starch milk with a starch content of 20% with water, add anhydrous sodium sulfate solution with a mass fraction of 10%, stir and heat in a water bath to 40°C for 10 minutes; while stirring, add a mass fraction of 5% NaOH solution to adjust the pH of the reaction system to above 10.5, quickly add propylene oxide with a volume fraction of 10-30%, put it in an airtight container at 35-40°C and 200rpm for etherification reaction for 21-24 hours; Then adjust the pH of the starch milk to 5.5 with dilute hydrochloric acid with a mass fraction of 10%; discard the supernatant after centrifugation, add twice the volume of water to centrifuge and wash 3 times, and dry and react at 40-45°C for 10-12 hours to obtain modified starch;

S3. Configure a starch solution with a mass fraction of 10-20%, and the starch is composed of the following components in mass percentages: 30-60% modified starch and 40-70% high amylose; put the starch solution at 93-97°C Stir the sol for 40 minutes, dip in glue after heat preservation and defoaming, dry at 35-38°C for 6-9 hours, and then release the mold to obtain starch-based hard capsules.

In the process of preparing starch hard capsules by traditional dipping and forming methods, the biggest difficulty is that the viscosity of the starch solution is too high and it is difficult to control the thickness. And the present invention can reduce the viscosity of starch by acid hydrolysis, can make the starch paste liquid of higher concentration, easy film-forming; The gelatinization temperature of the final modified starch is low, and the starch molecules can be well dispersed and dissolved after heating to form a starch paste with stable fluidity and viscosity. The film formed by the starch paste is transparent, flexible, smooth, and has good folding resistance. Therefore, after acid hydrolysis, etherification and other complex modifications of starch, the properties of the two modified starches can be optimized to obtain better gelling ability and mechanical strength, making them close to the properties of gelatin. High amylose starch with an amylose content of 80% is used as the matrix, and modified starch is used as the reinforcement phase. Through self-reinforcement, not only the mechanical properties of the capsules can be improved, but also their biocompatibility will not be affected. These three key process technologies solve the problems of high viscosity and poor film-forming properties of starch as capsules, and improve the quality of starch capsules.

Preferably, the starch described in S1 is any one or more of corn starch, tapioca starch, and potato starch.

Preferably, the high amylose starch in S3 is any one or more of high amylose corn starch G80, tapioca starch or potato starch with higher amylose content.

More preferably, the starch in S1 is corn starch, and the high-amylose starch in S3 is high-amylose corn starch G80.

The present inventor finds in the exploration to the technology that traditional dipping forming method prepares starch hard capsule, the kind and consumption of acid, the concentration of alkali, the selection of epoxide, the proportioning of matrix and reinforcing phase, the temperature of acidolysis reaction and Time, preparation parameters such as the temperature and time of the etherification reaction have a great influence on the transparency, toughness, friability, tightness and disintegration time limit of the final starch-based hard capsules. If the reaction temperature is too low, the reaction rate is too slow, and the temperature is too high, starch is easy to gelatinize. Through the optimization of these series of conditions, the present invention finally obtains the most preferred preparation parameters, and prepares starch-based hard capsules with high transparency, smooth surface, good folding resistance and short disintegration time limit.

Preferably, the reaction temperature of the acid hydrolysis in S1 is 40° C., and the reaction time is 12 hours.

Preferably, the volume fraction of propylene oxide in S2 is 20%.

Preferably, the etherification reaction temperature in S2 is 40° C., and the reaction time is 22 hours.

Preferably, the centrifugation speed in S1 and S2 is 5000r/min, and the centrifugation time is 10min.

Preferably, the starch in S3 consists of the following components in mass percentage: 40% modified starch and 60% high amylose.

Preferably, the temperature of the sol in S3 is 95°C.

Preferably, the drying temperature in S3 is 35° C., and the drying time is 6 hours.

The starch-based hard capsule prepared by the above method meets the relevant national standards, and has the advantages of high transparency, smooth surface, good folding resistance, short disintegration time limit and the like. Therefore, the present invention also claims the application of the starch-based hard capsules prepared by the method in the preparation of medicines, health products and functional foods.

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

The method provided by the present invention uses acid hydrolysis and etherification compound modification to treat starch, reduces the viscosity of starch, and improves the film-forming performance of starch at the same time; adopts high amylose starch with an amylose content of 80% as the matrix, and the modified starch is used to enhance Phase, starch-based hard capsules were prepared by traditional dipping and forming techniques. The starch-based hard capsule prepared by the method of the invention not only has the advantages of high transparency, smooth surface, good folding resistance, short disintegration time limit, etc., but also simplifies the production process, saves production cost, and is suitable for large-scale popularization and application.

Detailed ways

The present invention will be further elaborated below with specific examples, which are only used to explain the present invention, and are not intended to limit the scope of the present invention. The test methods used in the following examples are conventional methods unless otherwise specified; the materials and reagents used are commercially available reagents and materials unless otherwise specified.

Example 1

The present embodiment provides a kind of preparation method of starch-based hard capsule, comprises the steps:

1. Accurately weigh a certain amount of cornstarch, put it in a stainless steel blending container, use a hydrochloric acid solution with a concentration of 0.14mol/L to prepare the starch into starch milk with a starch content of 40%, and place it in a constant temperature shaking incubator at 35°C and 200rpm Acid hydrolysis in 11h. After the acid hydrolysis, the pH value of the starch milk was adjusted to 5.5 with 5% NaOH solution. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 10h , to get acid-thinned starch.

2. Take the acid-thinned starch obtained in step 1, make starch milk with a starch content of 20% with distilled water, pour it into a stainless steel reactor, add anhydrous sodium sulfate solution with a mass fraction of 10%, stir and heat in a water bath to a constant temperature of 40°C React for 10 minutes; add NaOH with a mass fraction of 5% while stirring to adjust the pH of the reaction system to above 10.5, then quickly add a certain amount of propylene oxide with a volume fraction of 10%, and place it in a closed container at 35°C and 200rpm The etherification reaction was carried out under the conditions for 21h. After the reaction, the pH of the starch milk was adjusted to 5.5 with dilute hydrochloric acid with a mass fraction of 10%. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 10h , to obtain modified starch.

3. Configure a starch solution with a mass fraction of 10-20%. The starch is composed of the following components in mass percentages: 30% modified starch and 70% high-amylose corn starch G80; put the starch solution into a 93°C constant temperature water bath Stir the sol in medium temperature for 40 minutes, dip in glue after heat preservation and defoaming, dry at 35°C for 8 hours, and then release the mold to obtain starch-based hard capsules, which meet the relevant national standards.

Example 2

The present embodiment provides a kind of preparation method of starch-based hard capsule, comprises the steps:

1. Accurately weigh a certain amount of cornstarch, place it in a stainless steel blending container, use a hydrochloric acid solution with a concentration of 0.14mol/L to prepare the starch into starch milk with a starch content of 40%, and place it in a constant temperature shaking incubator at 37°C and 200rpm Acid hydrolysis in 18h. After the acid hydrolysis, the pH value of the starch milk was adjusted to 5.5 with 5% NaOH solution. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 11h , to get acid-thinned starch.

2. Take the acid-thinned starch obtained in step 1, make starch milk with a starch content of 20% with distilled water, pour it into a stainless steel reactor, add anhydrous sodium sulfate solution with a mass fraction of 10%, stir and heat in a water bath to a constant temperature of 40°C React for 10 minutes; add NaOH with a mass fraction of 5% while stirring to adjust the pH of the reaction system to above 10.5, then quickly add a certain amount of propylene oxide with a volume fraction of 30%, and place it in a closed container at 37°C and 200rpm Under the conditions of etherification reaction 24h. After the reaction, the pH of the starch milk was adjusted to 5.5 with dilute hydrochloric acid with a mass fraction of 10%. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 11h , to obtain modified starch.

3. Configure a starch solution with a mass fraction of 10-20%. The starch is composed of the following components in mass percentages: 50% modified starch and 50% high-amylose corn starch G80; put the starch solution into a 97°C constant temperature water bath Stir the sol in medium temperature for 40 minutes, dip in glue after heat preservation and defoaming, dry at 38°C for 9 hours, and then release the mold to obtain starch-based hard capsules, which meet the relevant national standards.

Example 3

The present embodiment provides a kind of preparation method of starch-based hard capsule, comprises the steps:

1. Accurately weigh a certain amount of corn starch, put it in a stainless steel blending container, use a hydrochloric acid solution with a concentration of 0.14mol/L to prepare the starch into starch milk with a starch content of 40%, and place it in a constant temperature shaking incubator at 40°C and 200rpm Acid hydrolysis in 12h. After the acid hydrolysis, the pH value of the starch milk was adjusted to 5.5 with 5% NaOH solution. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 12h , to get acid-thinned starch.

2. Take the acid-thinned starch obtained in step 1, make starch milk with a starch content of 20% with distilled water, pour it into a stainless steel reactor, add anhydrous sodium sulfate solution with a mass fraction of 10%, stir and heat in a water bath to a constant temperature of 40°C React for 10 minutes; add NaOH with a mass fraction of 5% while stirring to adjust the pH of the reaction system to above 10.5, then quickly add a certain amount of propylene oxide with a volume fraction of 20%, and place it in a closed container at 40°C and 200rpm Under the conditions of etherification reaction 22h. After the reaction, the pH of the starch milk was adjusted to 5.5 with dilute hydrochloric acid with a mass fraction of 10%. First use a centrifuge to discard the supernatant, then centrifuge and wash with twice the volume of distilled water for 3 times, set the centrifuge speed to 5000r/min, and centrifuge for 10min, then react in an oven (40-45°C) for 12h , to obtain modified starch.

3. Configure a starch solution with a mass fraction of 10-20%. The starch is composed of the following components in mass percentages: 40% modified starch and 60% high-amylose corn starch G80; put the starch solution into a 95°C constant temperature water bath Stir the sol in medium temperature for 40 minutes, dip in glue after heat preservation and defoaming, dry at 35°C for 6 hours, and then release the mold to obtain starch-based hard capsules, which meet the relevant national standards.

performance analysis

The starch-based hard capsules prepared in Examples 1-3 were used for performance testing, and the results are shown in Table 1.

Table 1 The investigation result of embodiment 1～3 starch-based hard capsule

Appearance traits Friability Disintegration time limit Example 1 More transparent, smooth surface 3 10min Example 2 High transparency, smooth surface 2 9min Example 3 High transparency, smooth surface 0 8min

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the scope of the present invention. For those of ordinary skill in the art, on the basis of the above descriptions and ideas, they can also make There is no need to and cannot exhaustively list all the implementation manners for other changes or changes in different forms. All modifications, equivalent replacements and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the claims of the present invention.

Claims (10)

1. a kind of preparation method of starch base hard capsule, which is characterized in that include the following steps：

S1. take appropriate amount of starch that starch is configured to the starch milk of content of starch 40% with the hydrochloric acid solution of a concentration of 0.14mol/L, It is placed in 35~40 DEG C, acidolysis 6 under the conditions of 200rpm~for 24 hours；Use the NaOH solution that mass fraction is 5% by the pH tune of starch milk again To 5.5；Liquid is discarded supernatant after centrifugation, two volumes water centrifuge washing is added 3 times, in 40~45 DEG C of drying 10~12h of reaction, is obtained Acidified starch；

S2. take acidified starch obtained by S1, the starch milk of content of starch 20% be configured to water, be added mass fraction be 10% it is anhydrous Metabisulfite solution, stir and heating water bath to 40 DEG C reaction 10min；Mass fraction is added while stirring will for 5% NaOH solution The pH of reaction system is adjusted to 10.5 or more, rapidly join volume fraction be 10~30% propylene oxide, be placed in closed container in 35~40 DEG C, etherification reaction 21 under the conditions of 200rpm~for 24 hours；Use the dilute hydrochloric acid that mass fraction is 10% by the pH tune of starch milk again To 5.5；Liquid is discarded supernatant after centrifugation, two volumes water centrifuge washing is added 3 times, in 40~45 DEG C of drying 10~12h of reaction, is obtained Modified starch；

S3. the starch solution that configuration quality score is 10~20%, the starch are grouped as by each group of following mass percent： Modified starch 30~60% and high amylose starches 40~70%；Starch solution is stirred into colloidal sol 40min, heat preservation defoaming in 93~97 DEG C After dip in glue, after 35~38 DEG C of dry 6~9h demoulding to get starch base hard capsule.

2. preparation method according to claim 1, which is characterized in that starch described in S1 be cornstarch, tapioca, Potato starch any one or more of.

3. preparation method according to claim 1, which is characterized in that the reaction temperature of acidolysis described in S1 is 40 DEG C, instead It is 12h between seasonable.

4. preparation method according to claim 1, which is characterized in that the volume fraction of propylene oxide described in S2 is 20%.

5. preparation method according to claim 1, which is characterized in that the reaction temperature being etherified described in S2 is 40 DEG C, instead It is 22h between seasonable.

6. preparation method according to claim 1, which is characterized in that centrifugal rotational speed described in S1 and S2 is 5000r/min, Centrifugation time is 10min.

7. preparation method according to claim 1, which is characterized in that starch described in S3 is each by following mass percent Group is grouped as：Modified starch 40% and high amylose starches 60%.

8. preparation method according to claim 1, which is characterized in that the temperature of colloidal sol described in S3 is 95 DEG C.

9. preparation method according to claim 1, which is characterized in that dry temperature described in S3 is 35 DEG C, and the time is 6h。

10. the starch base hard capsule that any one of claim 1 to 9 the method is prepared is preparing drug, health products and work( Application in energy food.