CN112156154B - Instant gastrodia tuber granules and preparation method thereof - Google Patents
Instant gastrodia tuber granules and preparation method thereof Download PDFInfo
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- CN112156154B CN112156154B CN202011085150.9A CN202011085150A CN112156154B CN 112156154 B CN112156154 B CN 112156154B CN 202011085150 A CN202011085150 A CN 202011085150A CN 112156154 B CN112156154 B CN 112156154B
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- 239000008187 granular material Substances 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims description 11
- 241000305492 Gastrodia Species 0.000 title description 11
- 241000305491 Gastrodia elata Species 0.000 claims abstract description 47
- 239000000284 extract Substances 0.000 claims abstract description 34
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 24
- 229930195725 Mannitol Natural products 0.000 claims abstract description 24
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- 238000000034 method Methods 0.000 abstract description 15
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- 150000002989 phenols Chemical class 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
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- HEILIGJNYTWOHU-UHFFFAOYSA-N ethanol 2-hydroxybenzoic acid Chemical compound CCO.OC(=O)C1=CC=CC=C1O HEILIGJNYTWOHU-UHFFFAOYSA-N 0.000 description 1
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Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8988—Gastrodia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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Abstract
The invention discloses a gastrodia elata instant granule which comprises a gastrodia elata extract and auxiliary materials, wherein the auxiliary materials comprise cassava starch, mannitol and a flow aid, the weight ratio of the cassava starch to the mannitol is (0.5-2): 1, the weight ratio of the gastrodia elata extract to the cassava starch to the mannitol is 1-5: 1, preparing the gastrodia elata extract by adopting a complex enzyme enzymolysis method. The instant gastrodia elata granules prepared by the method are fragrant and sweet in smell, uniform in particle size, high in forming rate, good in solubility, fluidity and stability, better in compliance and longer in storage period, can be carried about and drunk instantly, are rich in various active ingredients such as polysaccharide, total phenol and gastrodin, and have various medical and health-care purposes of relieving dizziness and headache, resisting epilepsy, enhancing immunity, resisting oxidation and the like.
Description
Technical Field
The invention relates to a gastrodia tuber instant granule and a preparation method thereof.
Background
Gastrodia elata (g.elata) is a perennial herb parasitic plant of the genus gastrodiae of the family orchidaceae, and has been used for over 2000 years in China. The main medicinal part is the dry tuber, and has the effects of calming endogenous wind and relieving spasm, calming liver yang, and dispelling pathogenic wind and dredging collaterals. The rhizoma gastrodiae has complex chemical components, mainly contains phenol, glycosides and polysaccharides as active ingredients, and has pharmacological effects of relieving dizziness and headache, resisting epilepsy, enhancing immunity, resisting oxidation and the like. Gastrodine and p-hydroxybenzyl alcohol are important reference indexes established by quality standards of Gastrodia elata in Chinese pharmacopoeia (2015 edition). The Chinese pharmacopoeia and many modern gastrodia tuber products use the content of gastrodin as quality index, but the pharmacological action of gastrodia tuber is not equal to that of gastrodin, and other phenolic components and polysaccharides also have the activities of antioxidation, anticancer and antitumor.
The traditional extraction method mostly adopts a decoction method, but the method easily causes some heat-sensitive components in the gastrodia elata to lose activity, thereby reducing the drug effect. In recent years, many new technologies are introduced in the extraction of gastrodia elata, such as ultrasonic extraction, microwave-assisted extraction, ultrahigh-pressure extraction, enzymatic extraction and the like, wherein the enzymatic extraction is concerned about due to high extraction efficiency and certain conversion capacity on substances, but most of the existing enzymatic processes use commercial products such as industrial complex enzymes, amylases, cellulases, pectinases and the like, and few systematic studies on the types of enzymes and specific conditions of the enzymatic hydrolysis of gastrodia elata are carried out, so that the content of active ingredients such as polysaccharides, total phenols, gastrodin and the like in the extract is low.
The instant granules have the advantages of accurate dosage, convenient taking and carrying, convenient mechanized mass production and the like, and have a large consumption market. However, the traditional Chinese medicine extract has the characteristics of bitter taste, high viscosity, strong hygroscopicity and the like, so that the prepared granules have poor mouthfeel, low forming rate and short storage period, and the use compliance of consumers is reduced.
Disclosure of Invention
The invention aims to overcome the defects and provides instant gastrodia elata granules and a preparation method thereof. The product provided by the invention has the advantages of high dissolving speed, good taste, high forming rate, good fluidity, difficult moisture absorption, long storage life and the like, and the content of multi-index active ingredients such as polysaccharide, total phenol, gastrodin and the like in the product is higher, so that the product has better medical and health care purposes.
The above purpose is realized by the following technical scheme:
the rhizoma gastrodiae instant granules comprise a rhizoma gastrodiae extract and auxiliary materials, wherein the auxiliary materials comprise cassava starch, mannitol and a flow aid, and the weight ratio of the cassava starch to the mannitol is 0.5-2: 1, the weight ratio of the gastrodia elata extract to the cassava starch to the mannitol is 1-5: 1.
preferably, the weight ratio of the cassava starch to the mannitol is 1: 1, the weight ratio of the gastrodia elata extract to the cassava starch and the mannitol is 3: 1.
preferably, the glidant is aerosil, and the weight of the glidant is 1-2% of the instant granules.
Further preferably, the gastrodia elata extract is prepared by the following method: crushing the gastrodia elata into 100-300 times of fine powder, adding 20-50 times of water and 0.5-1.5% of complex enzyme according to the weight of the medicinal materials, performing enzymolysis for 1-3 hours at the temperature of 40-70 ℃ and under the condition of pH 3-7, filtering after the enzymolysis is finished, and performing spray drying on the filtrate to obtain powder, namely the gastrodia elata extract, wherein the complex enzyme consists of cellulase, hemicellulase and papain.
Preferably, the weight ratio of the cellulase to the hemicellulase to the papain is 1-3: 0.5-2: 0.5 to 2.
Preferably, the weight ratio of the cellulase to the hemicellulase to the papain is 2: 1: 1.
preferably, the gastrodia elata is crushed into fine powder of 200 meshes.
Preferably, 40 times of water and 0.9% of complex enzyme are added according to the weight of the medicinal materials, and the enzymolysis time is 2.5h under the conditions of the temperature of 60 ℃ and the pH value of 5.
A method for preparing rhizoma Gastrodiae instant granule comprises the following steps:
(1) preparing a gastrodia elata extract:
crushing gastrodia elata to 100-300 fine powder, adding 20-50 times of water and 0.5-1.5% of complex enzyme according to the weight of medicinal materials, performing enzymolysis for 1-3 hours at the temperature of 40-70 ℃ and under the condition of pH 3-7, filtering after the enzymolysis is finished, and performing spray drying on filtrate to obtain powder, namely the gastrodia elata extract, wherein the complex enzyme consists of cellulase, hemicellulase and papain, and the weight ratio of the cellulase to the hemicellulase to the papain is 1-3: 0.5-2: 0.5 to 2.
(2) Preparation of instant granules:
adding cassava starch and mannitol into the gastrodia elata extract, stirring and uniformly mixing, adding water to prepare a soft material, sieving and carrying out wet granulation, drying granules, adding a flow aid, and uniformly mixing to obtain the gastrodia elata chewable tablet, wherein the weight ratio of the cassava starch to the mannitol is 0.5-2: 1, the weight ratio of the gastrodia elata extract to the cassava starch to the mannitol is 1-5: 1, the glidant is micropowder silica gel, and the weight of the glidant is 1-2% of that of the instant granules.
The beneficial effects of the invention are:
(1) the instant gastrodia elata granules prepared by the method disclosed by the invention are fragrant and sweet in smell, uniform in particle size, high in forming rate, good in solubility, fluidity and stability, better in compliance and longer in storage period, and the granules can be carried about and instantly drunk, so that the instant gastrodia elata granules have a great market prospect.
(2) The instant gastrodia elata granules prepared by the method are rich in various active ingredients such as polysaccharide, total phenol, gastrodin and the like, and have various medical and health-care purposes such as dizziness and headache alleviation, epilepsy resistance, immunity enhancement, oxidation resistance and the like.
(3) The preparation method is green and efficient, simple to operate, free of toxic and harmful solvents, less in active ingredient damage and high in extraction efficiency.
Drawings
FIG. 1 shows the influence of the types of adjuvants on the molding rate of rhizoma Gastrodiae granules.
Fig. 2 shows the DPPH free radical scavenging experimental results of the instant gastrodia tuber granules.
Fig. 3 shows the result of hydroxyl radical scavenging experiment of instant gastrodia tuber granule.
Fig. 4 shows the result of the ABTS free radical scavenging experiment of the instant gastrodia tuber granules.
Detailed Description
In order to better understand the present invention, the following examples further illustrate the invention, but should not be understood as the definition of the invention, for those skilled in the art who make the above summary of the invention, some insubstantial modifications and adaptations are considered to fall within the scope of the invention.
EXAMPLE 1 selection of granule formulation
1. Selection of auxiliary Material types
First, the formulation of the instant granules was investigated, and the granules were granulated using corn starch, potato starch, tapioca starch, erythritol, mannitol, sorbitol, and xylitol as carriers, and the influence of the type of carrier on the granulation process and the granule molding rate, hygroscopicity, and flowability was investigated, and the results are shown in table 1. The gastrodia elata extracts are all commercially available products in the same batch, and the weight ratio of the gastrodia elata extracts to the auxiliary materials is 5: the granulation process uses wet granulation as is conventional in the art.
TABLE 1 Effect of different excipients on the preparation of granules
As can be seen from Table 1, the granules were seen in appearance as white tapioca starch, potato starch, corn starch and mannitol granules, and the erythritol, sorbitol and xylitol granules were seen in appearance as yellow or pale yellow, in which erythritol was slightly bonded, and agglomeration occurred more seriously between sorbitol and xylitol granules; from the odor and dissolution after hot water dissolution, corn starch and potato starch have a slight starch taste, whereas tapioca starch feels lighter, and mannitol, erythritol, sorbitol and xylitol have a sweet odor and a sweet and cool mouthfeel.
As can be seen from figure 1, the molding rate of the mannitol particles is the highest, and reaches more than 80%, because the mannitol can increase the sweet taste of the particles and has better molding property, but the mannitol is expensive, and compared with starch, the starch is more easily obtained and is cheaper, the cassava starch and the mannitol are finally selected as carriers of the gastrodia elata extract in the granules.
2. Selection of the amount of auxiliary materials
Uniformity experiment design, as shown in table 2, the gastrodia elata extract and the auxiliary materials tapioca starch and mannitol are mixed uniformly according to a certain proportion to prepare instant granules.
TABLE 2 Experimental design for homogeneity
TABLE 3 results of homogeneity experiments
Note that, the calculation formula of the composite score: the total score (molding ratio measurement value/95) × 0.5+ (10/hygroscopicity measurement value) × 0.3+ (20/angle of repose measurement value) × 0.2 (wherein 95, 10, 20 represent molding ratio, hygroscopicity and angle of repose optimum values, respectively)
As can be seen from table 3, the total score of sample 4 is 92.93, which is the highest value of the sample, i.e. the ratio of the gastrodia elata extract to the auxiliary materials is 3: 1, cassava starch: mannitol is 1: 1, the molding ratio, hygroscopicity and angle of repose were all good, indicating that the yield of granules was higher and the stability and flowability were better under these conditions.
Example 2 preparation of Gastrodia elata extract
Polysaccharide, gastrodin and total phenol are main active ingredients of the gastrodia elata, the content of the active ingredients in the existing extract is low, although an enzymolysis method is a conventional method for improving the content of the active ingredients of the medicinal material extract, most of the existing enzymolysis processes for the gastrodia elata only investigate one or two active ingredients, and still have low content of part of the active ingredients.
(1) Selection of particle size for comminution
Pulverizing rhizoma Gastrodiae to 20, 100, 150, 200, 300 mesh with ball mill, performing enzymolysis with cellulase for 2 hr under the same conditions, filtering, spray drying, and determining polysaccharide, gastrodin and total phenol content in the extract, the results are shown in Table 4.
TABLE 4 influence of rhizoma Gastrodiae particle size on enzymolysis effect
As can be seen from table 1, when the particle size of the gastrodia elata powder reaches 200 meshes, the content of polysaccharide, gastrodin and total phenol in the enzymatic hydrolysis product is close to the maximum value, the difference from the enzymatic hydrolysis effect when the gastrodia elata powder is crushed to 300 meshes is not large, and 200 meshes are selected as the optimal gastrodia elata crushing particle size in order to save mechanical cost.
(2) Selection of compound enzyme type and proportion
According to the literature and the results of preliminary experiments, cellulase, hemicellulase, pectinase, amylase and papain are selected to carry out enzymolysis experiments under the same conditions. Filtering after enzymolysis, spray drying, and determining the content (%) of polysaccharide, gastrodin and total phenols in the extract, wherein the results are shown in Table 5.
TABLE 5 Effect of Complex enzyme species on the enzymolysis Effect
| Class of enzyme | Polysaccharides | Gastrodin | Total phenols |
| Cellulase + pectinase (1: 1) | 37.39 | 3.37 | 0.66 |
| Cellulase + papain (1: 1) | 30.28 | 3.14 | 0.57 |
| Amylase | 29.96 | 2.89 | 0.38 |
| Hemicellulase + papain (1: 1) | 26.56 | 2.61 | 0.32 |
| Cellulase + hemicellulase (1: 1) | 39.50 | 3.21 | 0.63 |
| Cellulase + amylase (1: 1) | 40.27 | 3.38 | 0.70 |
| Amylase + papain (1: 1) | 28.15 | 2.71 | 0.37 |
| Pectinase + amylase (1: 1) | 31.26 | 2.94 | 0.46 |
| Cellulase + amylase + pectinase (1: 1: 1) | 31.78 | 2.94 | 0.49 |
| Amylase + pectinase + papain (1: 1: 1) | 30.05 | 2.86 | 0.45 |
| Cellulase + hemicellulase + papain (1: 1: 1) | 48.49 | 2.96 | 0.54 |
| Cellulase + hemicellulase + papain (2: 1: 1) | 51.56 | 3.59 | 0.80 |
| Cellulase + hemicellulase + papain (3: 2: 1) | 46.33 | 3.47 | 0.71 |
| Cellulase + hemicellulase + papain (1: 2: 2) | 43.89 | 2.83 | 0.69 |
| Cellulase + hemicellulase + papain (2: 2: 1) | 50.07 | 3.33 | 0.70 |
As can be seen from table 2, under the action of the cellulase, hemicellulase and papain complex enzyme, the content of polysaccharide, gastrodin and total phenols in the gastrodia elata extract is relatively high, and when the weight ratio of the three enzymes is 2: 1: 1, the comprehensive effect is the best, so the complex enzyme is selected for enzymolysis and subsequent experiments are carried out.
(3) Optimization of enzymolysis conditions
On the basis of determining the kind of the complex enzyme, the feed-liquid ratio, the addition amount of the complex enzyme, the enzymolysis temperature, the pH value, the enzymolysis time and the like which influence the enzymolysis effect are further optimized, and the results are shown in tables 6 and 7.
TABLE 6 enzymatic hydrolysis conditions for each test sample
| Sample number | Ratio of material to liquid | Enzyme addition amount | Temperature of enzymolysis | pH | Time of enzymolysis |
| 1 | 1：50 | 1.2 | 50 | 6 | 3 |
| 2 | 1：20 | 0.7 | 65 | 4 | 1.5 |
| 3 | 1：40 | 0.9 | 60 | 5 | 2.5 |
| 4 | 1：30 | 1.5 | 55 | 3 | 1 |
| 5 | 1：25 | 0.5 | 70 | 7 | 1.5 |
| 6 | 1：45 | 1.0 | 45 | 4.5 | 2.5 |
| 7 | 1：35 | 0.8 | 40 | 5.5 | 2 |
TABLE 7 Effect of enzymatic conditions on the content of three active ingredients
| Sample number | Polysaccharides | Gastrodin | Total phenols |
| 1 | 49.01 | 3.67 | 0.77 |
| 2 | 43.47 | 3.58 | 0.73 |
| 3 | 61.93 | 3.89 | 0.88 |
| 4 | 48.56 | 3.64 | 0.74 |
| 5 | 51.07 | 3.51 | 0.71 |
| 6 | 52.71 | 3.62 | 0.76 |
| 7 | 57.83 | 3.61 | 0.75 |
As can be seen from the above results, test 3 is: the ratio of material to liquid is 1: 40. the enzyme addition amount is 0.9%, the enzymolysis temperature is 60 ℃, the pH is 5, and the enzymolysis time is 2.5h, and the content of three active ingredients in the extract is higher.
Example 3
A rhizoma Gastrodiae instant granule is prepared by the following steps:
(1) preparing a gastrodia elata extract:
pulverizing rhizoma Gastrodiae to fine powder of 200, adding 40 times of water and 0.9% complex enzyme according to the weight of the medicinal materials, performing enzymolysis at 60 deg.C and pH 5 for 2.5h, filtering after enzymolysis, and spray drying the filtrate to obtain powder, i.e. rhizoma Gastrodiae extract, wherein the complex enzyme comprises cellulase, hemicellulase and papain, the weight ratio of cellulase, hemicellulase and papain is 2: 1: 1.
(2) Preparation of instant granules:
according to the weight ratio of the gastrodia elata extract to the auxiliary materials of 3: 1, adding an auxiliary material into the gastrodia elata extract, wherein the auxiliary material consists of cassava starch and mannitol in a weight ratio of 1: 1, stirring and mixing uniformly, adding water to prepare a soft material, performing wet granulation by a 20-mesh screen, drying granules, adding 1.5 percent (by weight) of superfine silica gel powder, and mixing uniformly to obtain the finished product.
Detecting antioxidant activity of rhizoma Gastrodiae instant granule, using Vc granule and rhizoma Gastrodiae instant granule prepared by hot water reflux extraction method as control, the detection method comprises:
weighing 2.5g of rhizoma gastrodiae instant granules under the optimal enzymolysis condition, adding 100mL of pure water to prepare a solution with the concentration of 25mg/mL, and diluting to 5, 10, 15, 20 and 25 mg/mL.
(1) DPPH free radical scavenging experiment
Taking 1.00mL of rhizoma gastrodiae sample and 1.00mL of 0.2mmol/L DPPH solution, putting the mixture into a 10.00mL centrifuge tube, fully and uniformly mixing, standing the mixture at room temperature in a dark place for 30min, and then centrifuging the mixture for 5min at 10000 r/min. The supernatant was measured for absorbance A at a wavelength of 517 nm. Determining the absorbance A of the mixture of 1.00mL of sample and 1.00mL of absolute ethyl alcohol by the same methodbAnd the absorbance A of 1.00mL of DPPH solution and 1.00mL of ultrapure water0. Triplicate determinations were made. DPPH free radical clearance was calculated as follows:
(2) Hydroxy radical scavenging test
1.00mL of 6.00mmol/L FeSO are added into a centrifuge tube in sequence4·7H2O solution, 1.00mL of 6.00mmol/L salicylic acid-ethanol solution and 1.00mL of sample diluents with different concentrations are mixed uniformly immediately, and finally 1.00mL of 6.00mmol/L H is added2O2The solution is subjected to 37 deg.C water bath for 30min, and the absorbance A is measured at 510nm wavelengthXUltrapure water was used as a reference. H is replaced by ultrapure water for the same method measurement2O2Absorbance A in solutionX0And absorbance A when the sample diluent was replaced with ultrapure water0. Triplicate determinations were made. Hydroxyl radical clearance was calculated as follows:
(3) ABTS free radical scavenging experiments
And mixing the 7.00mmol/L ABTS solution and the 2.45mmol/L potassium persulfate solution in equal volume, and reacting for 16h in the dark to obtain an ABTS mother liquor. The ABTS stock was diluted with phosphate buffer to an absorbance of 0.70. + -. 0.02 at 734 nm. Accurately sucking 1.00mL of sample diluent with different concentrations and 1.00mL of ABTS solution, mixing the solution vigorously, standing the mixture at room temperature in a dark place for 6min, and immediately measuring the absorbance A at 734 nm. ABTS free radical clearance was calculated as follows:
wherein: a is the absorbance of 1.00mLABTS +1.00mL of sample solution; a. theb1.00mL of H2Absorbance of O +1.00mL of sample solution; a. the01.00mLABTS +1.00mL H2And (4) absorbance of O.
As can be seen from FIGS. 2-4, the instant granules of rhizoma Gastrodiae prepared by complex enzymolysis can be used for DPPH*The clearance rate of free radicals is equivalent to that of the gastrodia tuber instant granules prepared by a hot water reflux extraction method, but the clearance rate of the free radicals is equivalent to that of the gastrodia tuber instant granules prepared by the hot water reflux extraction method*OH clearance and ABTS*+The clearance rate of free radicals is obviously higher than that of the latter, especially in ABTS*+In the aspect of free radical clearance, the gastrodia tuber instant granules prepared by the invention are equivalent to Vc.
Claims (1)
1. A preparation method of instant gastrodia elata granules is characterized by comprising the following steps:
(1) preparing a gastrodia elata extract:
pulverizing rhizoma Gastrodiae to fine powder of 200 meshes, adding 40 times of water and 0.9% complex enzyme according to the weight of the medicinal materials, performing enzymolysis at 60 deg.C and pH 5 for 2.5h, filtering after the enzymolysis is finished, and spray drying the filtrate to obtain powder, i.e. rhizoma Gastrodiae extract, wherein the complex enzyme comprises cellulase, hemicellulase and papain, the weight ratio of cellulase, hemicellulase and papain is 2: 1: 1;
(2) preparation of instant granules:
adding cassava starch and mannitol into the gastrodia elata extract, stirring and uniformly mixing, adding water to prepare a soft material, sieving and performing wet granulation, drying granules, adding a glidant, and uniformly mixing to obtain the gastrodia elata chewable tablet, wherein the weight ratio of the cassava starch to the mannitol is 1: 1, the weight ratio of the gastrodia elata extract to the cassava starch and the mannitol is 3: 1, the glidant is micropowder silica gel, and the weight of the glidant is 1-2% of that of the instant granules.
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