CA2872050C - Mixing and extruding method for preparing starch softgel capsules - Google Patents

Abstract

The invention discloses an extrusion method for preparing starch-based softgel capsules, which, specifically, includes the following 2 steps: 1, co-extruding the starch premix and gel solution to form composite starch film. 2, processing two composite starch films into starch-based softgel capsules by rotary die process.

Description

9HUNAN 3.0-005 MIXING AND EXTRUDING METHOD FOR PREPARING
STARCH SOFTGEL CAPSULES
FIELD OF INVENTION
[0001] This invention relates to a preparation method of softgel capsules, more specifically, of non-gelatin softgel capsules.
BACKGROUND OF THE INVENTION

[0002] Softgel capsules are generally used for enclosing the medicines that should not directly contact esophagus and that must be disintegrated in the stomach or intestines. At present, most softgel capsules used for medicines or dietary supplements are made of gelatin extracted from animal skins or the bones, and the extraction process involves acid or alkali treatment, which unavoidably generates animal protein residues. These residues will interact with the enclosed content in the softgel capsules and thus lead to negative consequences such as drug spoilage.

[0003] In addition, animal-source gelatin is not acceptable to vegetarians and/or the people with Islamic and Jewish beliefs, and those with allergic constitution should also avoid intake of gelatin products.

[0004] As starch is made from rich resource of plants, its price is far lower than that of gelatin. The starch, when modified, achieves better gelation performance and mechanical strength, which makes its characteristics close to that of the gelatin. Since starch-based softgel capsules can overcome the shortcomings of existing gelatin 9HUNAN 3.0-005 softgel capsules and at the same time has the advantage of low cost, It is worthy of popularization.

[0005] By the existing technologies, Pat. No. CN1483393A discloses a starch softgel capsule preparation method, wherein the starch and starch derivatives are dissolved in water and heated to 60-65 C, and then add plasticizer and put the mixed solution into the heat-insulated trough to prepare the softgel capsule shell using Glue stick method.

[0006] Pat. No. ON 103055317A discloses a preparation method of instant plant softgel capsules wherein the raw material is dissolved in water and then made into softgel capsules using softgel machine.

[0007] The general practice in the above mentioned methods is to add water to the material to form aqueous solution, which is then input to the softgel capsule machine to form softgel capsules. However, due to the poor water-solubility of starch and other polymers, it is not easy to obtain uniform mixture using water phase---thus affects the quality of the finished product and particularly, leads to the problems like uneven softgel capsule shells and improper encapsulation.

[0008] In this invention, the raw material is mixed in a screw extruder. The advantage of this mixing method lies in that the starch (or starch derivatives) and additives are heated to a relatively higher temperature inside the extruder and melt into a semi-solid form, which is then repeatedly pressed, kneaded, cut, and blended by the screw. The combined effects of these actions can change the molecular chain structure of the starch and lead to solid phase 9HUNAN 3 . 0 -0 0 5 chemical reaction, and thus further improves the mechanical strength of the starch. Additionally, the extruded film has uniform thickness, which overcomes such deficiency as uneven shell thickness and improper encapsulation. It is a great technical progress!
OBJECT OF THE INVENTION

[0009] It is therefore an object of the present invention to provide a method of starch-based softgel capsule preparation, aiming to tackle the existing problems of uneven mixture and improper encapsulation in conventional mixing technologies.

[0010] The invention includes the following steps:

[0011] ( a ) Preparation of composite starch film: Mix starch, anti-caking agent, and gel solution to form starch-based premix, which is then transferred to the extruder to form composite starch film.

[0012] (b) Preparation of starch-based softgel capsules: Process two pieces of composite starch films to starch-based softgel capsules using rotary die process.
DETAILED DESCRIPTION OF EACH STEP

[0013] Step 1: Preparation of composite starch film

[0014] The composite starch film is prepared by mixing the starch and the gel solution through the following steps:

[0015] Prepare the gel solution by dissolving gel, water retention agent, emulsifier, and gelatinization agent in water, and mix the 9HUNAN 3.0-005 starch and anti-caking agent for 5minutes in the high-speed mixer at the speed of 1500-2000rpm and under the temperature of 60 ct; then slowly add the gel solution into the high-speed mixer while keep stirring for another 5minutes to get the starch-based premix ready;
Feeds the starch-based premix into the double screw-type extruder, through which, the starch-based premix is extruded out as granules.
Process the granules into a composite film by single-type extruder.

[0016] The raw material is native or modified starch (modified by chemical or physical process), preferably, modified corn starch, potato starch, tapioca starch, wheat starch, mung bean starch, rice starch, or oxidized mung bean starch, of which, mung bean starch should be the priority choice. The suggested carboxyl group content in the modified starch is in the range of 0.2%-0.3%.

[0017] The said gel is one or a combination of the substances selected from the group consisting of amylopectin, gellan gum, carrageenan, xanthan gum, and guar gum , among which, carrageenan is the priority choice.

[0018] For starch, preferably oxidized mung bean starch, and for gel, preferably carrageenan gel.

[0019] The said water retention agent in Step 1 is pharmaceutical glycerin or pharmaceutical grade sorbitol.

[0020] The said anti-caking agent mentioned in Step 1 is pharmaceutical stearic acid or fatty glyceride

[0021] The said emulsifier in Step 1 is ionic emulsifier, preferably pharmaceutical alkali metal salts sulfate or 91-1LJNAN 3.0-005 alkali metal salts sulfonate, such as pharmaceutical sodium dodecyl sulfonate or pharmaceutical sodium dodecyl sulfate.

[0022] The said gelatinization agent Step 1 is deionized water.

[0023] The parameters of the double screw-type extruder mentioned in Step 1 are as follows: material temperature, 80-170 C; screw rotation speed, 60-400 rpm; (Optimized speed should be: 90-160 C, 100-150 C, 100-140 C, 110-130 C, 120 C, 125 C.)

[0024] The parameters of the single screw-type extruder mentioned in Step 1 are as follows: material temperature, 80-165 C; screw rotation speed, 60-300 rpm; (Optimized speed should be: 90-160 C, 100-150 C, 100-140 C, 110-130 C, 100 C, 105 C.) .

[0025] The composition of the gel solution:

[0026] Gel: 15%-25% of the gel solution (by weight)

[0027] Water retaining agent: 1%-5% of the gel solution (by weight)

[0028] Emulsifier: 0.02-1% of the gel solution (by weight)

[0029] Deionized water.

[0030] Step 2: Preparation of starch-based softgel--Rotary die method

[0031] Feed two pieces of composite starch films into the two adjoining cylinder moulds respectively; adjust the mould temperature to 40-90 C and start up the machine. Then, the two cylinder moulds drive the two composite films spinning inward in different direction.
The grooves on the mould can be vacuumed to make the composite starch =
9HUNAN 3.0-005 film adhered to the mould form pits, which are then pressed by the mould into softgel capsules with cavities. At the same time of the softgel capsule formation, the softgel capsule content is filled from right above the junction of the two cylinder moulds.

[0032] The advantage of this invention is that, the premixed material is thoroughly and uniformly mixed, stirred, kneaded, and blended through the extruder, and meanwhile, the extruder ensures continuous production, and thus reduces the cost.

[0033] The starch-based softgel capsule prepared according to this present invention can be used for the preparation of drugs, dietary supplements, and functional foods.
EXAMPLES

[0034] The examples set forth below further explain the content of this present invention and the nature of the product produced by this invention. The following examples are illustrative, and should not be viewed as limiting the scope of the present invention

[0035] Example 1:

[0036] Raw materials and their weight ratio:

[0037] Gel: carrageenan, 2%;

[0038] Starch: corn starch, 75%;

[0039] Water retaining agent: pharmaceutical glycerin, 1%;

[0040] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0041] Emulsifier: pharmaceutical sodium dodecyl sulfate, 0.02%;

9HUNAN 3.0-005

[0042] Gelatinization agent: Deionized water, 21.78%.

[0043] The parameters of the double screw-type extruder are as follows

[0044] The rotation speed is set to 350 RPM, and the designed temperature for each slider is as follows:

[0045] Slide 1: 25 C

[0046] Slide 2-3: 110 C

[0047] Slide 4-6: 145 C

[0048] Slide 7-9: 165 C

[0049] Slide 10-12: 160 C

[0050] Nozzle: 160 C

[0051] The parameters of the single screw-type extruder are as follows

[0052] Extrudes at the rotation speed of 300 RPM, and the designed temperature is 120 C.

[0053] Steps to prepare composite films: Prepare the gel solution by dissolving gel, water retention agent, emulsifier, and gelatinization agent in water, and mix the starch and anti-caking agent for 5 minutes in the high-speed mixer at the speed of 1500-2000rpm and under the temperature of 60 C; Then slowly add the gel solution into the high-speed mixer while keep stirring for another 5 minutes to get the starch-based premix ready; Feeds the starch-based premix into the double screw-type extruder to extrude 9HUNAN 3.0-005 the premixed material into mixed starch granules, which are then made into composite films made of starch and gel solution by single screw-type extruder. Starch-based softgel capsules preparation: Put the composite film into the rotary die with temperature control device to make starch-based softgel. The mold temperature is set at 60 C.

[0054] Example 2

[0055] Raw materials and their weight ratio:

[0056] Gel: Xanthan gum, 2%;

[0057] Starch: corn starch, 75%;

[0058] Water retaining agent: pharmaceutical glycerin, 3%;

[0059] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0060] Emulsifier: pharmaceutical grade twelve sodium alkyl sulfate, 0.02%;

[0061] Gelatinization agent: Deionized water, 19.78%;

[0062] Other parameters and processes are the same as those in Example 1.

[0063] Example 3

[0064] Raw materials and their weight ratio:

[0065] Gel: guar gum, 2%;

[0066] Starch: starch, 75%;

[0067] Water retaining agent: pharmaceutical grade glycerin, 1%;

9HUNAN 3.0-005

[0068] Anti-caking agent: pharmaceutical grade stearic acid, 0.5%;

[0069] Emulsifier: pharmaceutical grade twelve sodium alkyl sulfate, 0.02%;

[0070] Gelatinization agent: Deionized water, 21.48%;

[0071] Other parameters and processes are the same as those in Example 1.

[0072] Example 4

[0073] Raw materials and their weight ratio:

[0074] Gel: carrageenan, 2%;

[0075] Starch: oxidized mung bean starch 75%, with carboxyl content of 0.1%

[0076] Water retaining agent: pharmaceutical glycerin, 1%;

[0077] Anti-caking agent: pharmaceutical stearic acid, 0.5%;

[0078] Emulsifier: Gelatinization agent: pharmaceutical sodium dodecyl sulfate, 0.3%;

[0079] Gelatinization: Deionized water, 21.2%;

[0080] Other parameters and processes are the same as those in Example 1.

[0081] Example 5

[0082] Raw materials and their weight ratio:

[0083] Gel: cross-linking cassava starch, 10%;

9HUNAN 3.0-005

[0084] Starch: wheat starch, 65%;

[0085] Water retaining agent: pharmaceutical glycerin, 0%;

[0086] Anti-caking agent: pharmaceutical stearic acid, 0%;

[0087] Emulsifier: pharmaceutical sodium dodecyl sulfate.

[0088] Gelatinization agent: Deionized water, 25%;

[0089] Other parameters and processes are the same as Example 1.

[0090] Example 6

[0091] Raw materials and their weight ratio:

[0092] Gel: carrageenan, 2%;

[0093] Starch: oxidized mung bean starch, 80% with carboxyl content of 0.4%

[0094] Water retaining agent: pharmaceutical glycerin, 1%;

[0095] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0096] Emulsifier: pharmaceutical sodium dodecyl sulfate, 0.02%.

[0097] Gelatinization agent: deionized water. 16.78%.

[0098] Other parameters and processes are the same as those in Example 1.

[0099] Example 7:

[0100] Raw materials and their weight ratio:

[0101] Gel: carrageenan, 2%;

9HUNAN 3.0-005

[0102] Starch: oxidized mung bean starch, 80% with carboxyl content of 0.28.

[0103] Water retaining agent: pharmaceutical glycerin, 1%;

[0104] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0105] Emulsifier: pharmaceutical sodium dodecyl sulfate, 0.02%;

[0106] Gelatinization agent: Deionized water, 16.78%.

[0107] Other parameters and processes are the same as those in Example 1.

[0108] Example 8

[0109] Raw materials and their weight ratio:

[0110] Gel: guar gum, 2%;

[0111] Starch: oxidized mung bean starch, 80% with carboxyl content of 0.28.

[0112] Water retaining agent: pharmaceutical grade glycerin, 1%;

[0113] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0114] Emulsifier: pharmaceutical sodium dodecyl sulfate, 0.02%;

[0115] Gelatinization agent: Deionized water. 16.78%.

[0116] Other parameters and processes are the same as Example 1.

[0117] Comparative Example.

[0118] Raw materials and their weight ratio:

[0119] Gel: carrageenan, 2%;

=
9HUNAN 3.0-005

[0120] Starch: cassava starch, 75%;

[0121] Water retaining agent: pharmaceutical glycerin, 1%;

[0122] Anti-caking agent: pharmaceutical stearic acid, 0.2%;

[0123] Emulsifier: pharmaceutical sodium dodecyl sulfate, 0.02%;

[0124] Gelatinization agent: Deionized water, 21.78%.

[0125] Put the above materials into a sandwich-type pot and stir, and then add the same amount (by weight) of deionized water, stir and steam heat to make it melt. Maintain the temperature for 1 - 2 hours and allow it to stay static until the foams float up. Keep warm and filter to make it paste-like solution for use. Apply conventional method to prepare softgel capsules.

[0126] The softgel capsule prepared by the invention is used for encapsulating essential oil. The following result is based on a 6-month long examination on the stability of the softgel capsules within specific time and on the condition of ( T = 40 2 C, RH =75% ), using essential oil of ligusticumchuanxionghort as sample material.
Use the content of ligustilide as the index to inspect the characters and disintegration time. Disintegration time measurement: follow the method A in the appendix X of Chinese Pharmacopoeia 2010 2'1 edition, according to which, the softgel capsuleshould be completely disintegrated within 1 hour; Ligustilide content measurement: apply regular method to measure ligustilide content. Calculate the average value of ligustilide content and disintegration time (sample size:
softgel capsules) 9HUNAN 3.0-005

[0127] Table 1 Stability Study Examples Time Appearance disintegra Ligustilid (unit: tion time e content month) limit Examples 0 Clean and leakage 35 100.2%
free 1 Clean and leakage 35 99.8%
free 3 Clean and leakage 37 92.5%
free 6 Clean and leakage 40 83.1%
free Examples 0 Clean and leakage 35 100.5%
free 1 Clean and leakage 36 98.3%
free 3 Clean and leakage 38 93.5%
free 6 Clean and leakage 41 84.1%
free Examples 0 Clean and leakage 34 99.9%
free 1 Clean and leakage 36 97.9%
free 3 Clean and leakage 39 90.6%
free 6 Clean and leakage 42 83.9%
free Examples 0 Clean and leakage 30 100.5%
free 1 Clean and leakage 30 99.5%
free 3 Clean and leakage 32 98.9%
free 6 Clean and leakage 37 90.6%
free Examples 0 Clean and leakage 37 99.8%
free 9HUNAN 3.0-005 1 Clean and leakage 38 96.9%
free 3 Clean and leakage 39 90.2%
free 6 Clean and leakage 43 82.9%
free Examples 0 Clean and leakage 29 100.1%
free 1 Clean and leakage 30 99.6%
free 3 Clean and leakage 32 98.7%
free 6 Clean and leakage 37 91.2%
free Examples 0 Clean and leakage 25 100.3%
free 1 Clean and leakage 27 99.8%
free 3 Clean and leakage 30 99.0%
free 6 Clean and leakage 31 98.7%
free Examples 0 Clean and leakage 38 100.1%
free 1 Clean and leakage 39 98.1%
free 3 Clean and leakage 41 93.2%
free 6 Clean and leakage 43 83.2%
free Comparati 0 Clean and leakage 52 99.9%
ye Example free 1 Clean and leakage 55 92.7%
free 3 Slight leakage 67 84.6%
on outer wall 6 Seriousleakageon 76 70.3%
outer wall

Claims (5)

1. A method for preparing starch-based softgel capsules, comprising:
(1) preparing composite starch extrusion film comprising:
(a) forming a premixed material comprising:
(i) mixing a starch and an anti-caking agent in a high speed mixer at a speed of 1500-2000rpm, and (ii) adding a gel solution into the high speed mixer, wherein the gel solution comprises:
a gel in the amount of 15%-25% by weight of the gel solution, a water retention agent in the amount of 1%-5% by weight of the gel solution, an ionic emulsifier in the amount of 0.02%- 1 % by weight of the gel solution, and deionized water;
(b) feeding the premixed material into a double-screw type extruder;
(c) extruding the premixed material through the double-screw extruder to produce starch granules, wherein the double-screw extruder is set to a temperature of 80-170° C and a rotation speed is 60-450 rpm;
(d) processing the starch granules through a single-screw extruder to form pieces of the composite starch extrusion film, wherein the single-screw extruder is set to a temperature of 80-165 °C and a rotation speed is 100-380 rpm;
(2) preparing starch-based sofigel capsules comprising:
processing two pieces of the composite starch extrusion film prepared by step 1 into a starch-based softgel capsule by a rotary die process;
wherein the starch-based softgel capsule comprises the starch in the amount of at least 65%
by weight.

2. The method according to claim 1, wherein the gel is one or a combination of substances selected from the group consisting of amylopectin, gellan gum, carrageenan, xanthan gum, and guar gum..

3. The method according to claim 1 or 2, wherein the emulsifier is an alkali metal sulfate or an alkali metal sulfonate and the anti-caking agent is pharmaceutical stearic acid or glycerol esters of fatty acids.

4. The method of claim 1, 2 or 3 wherein the starch-based softgel capsule comprises the starch in the amount of 65 to 80% by weight.

5. A starch-based softgel capsule prepared according to the method of any one of claims 1 to 4 for use in the preparation of drugs, dietary supplements, and functional foods.