CN109925296B - Coating method of traditional Chinese medicine pellets - Google Patents
Coating method of traditional Chinese medicine pellets Download PDFInfo
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Abstract
The invention provides a coating method of traditional Chinese medicine pellets, which comprises the steps of coating a layer of powder layer on the surfaces of pellets containing traditional Chinese medicine extracts by using pharmaceutically acceptable auxiliary materials, and then coating by adopting a fluidized bed coating technology; the coating method of the traditional Chinese medicine pellet can be used for coating various traditional Chinese medicine pills, is particularly suitable for the pellets containing traditional Chinese medicine extracts with larger viscosity, can obviously improve the problems of viscosity, bed collapse, color difference, color spots and the like in the fluidized bed coating process of the traditional Chinese medicine extract pellets, has the advantages of high pill forming rate, good formability, simple operation, low production cost, high efficiency and the like, and is suitable for industrial mass production application.
Description
Technical Field
The invention belongs to the field of medicine manufacturing, and particularly relates to a coating method of traditional Chinese medicine pellets.
Background
The traditional Chinese medicine pellet is a spherical or spheroidal preparation with the diameter of 0.5-1.5mm and generally not more than 2.5mm, and has the technical advantages of simple production process, good fluidity, beautiful appearance, strong stability and the like. Belonging to a multiple unit type drug delivery system, has a plurality of advantages compared with a single dose type drug delivery system; each administration dose usually contains dozens or hundreds of pellets, and the drug release behavior is the sum of the individual pellets; the distribution area in the body is large, the bioavailability is high, and the intestinal irritation is small; long retention time in stomach, small particle size, small influence of food conveying rhythm on transportation and the like.
Because the micro-pills prepared from the traditional Chinese medicine extract or the traditional Chinese medicine powder generally have stronger hygroscopicity, the moisture absorption problem of the micro-pills is improved by adopting a film coating technology. For some traditional Chinese medicine pellets with bad smell or containing volatile oil, the smell can be covered or the loss of the volatile oil can be reduced by film coating. The most common coating method at present is a solvent coating method, which comprises an organic solvent coating and a water solvent coating, but the use of the organic solvent may cause solvent residue to influence the quality of the medicine, and the method has special requirements on the selection of the type of the organic solvent, thereby limiting the application of the organic solvent coating method to a certain extent; compared with organic solvent coating, the aqueous solvent coating does not need to use organic solvent, reduces the quality risk caused by solvent residue, reduces the coating cost, and gradually becomes the mainstream choice of the traditional Chinese medicine pellet coating technology.
Coating of traditional Chinese medicine pellets is usually carried out by adopting a coating pan or a fluidized bed, however, most of extracts of traditional Chinese medicine preparations, especially traditional Chinese medicine compound preparations, are extractum, fluid extract or amorphous powder, and the materials generally have high viscosity and hygroscopicity and unstable physicochemical properties, so that the problems of adhesion, bed collapse, gun mouth blockage, low pill forming rate and the like are easily caused in the process of coating by using the fluidized bed, and great difficulty is brought to coating of the traditional Chinese medicine pellets. For example, the traditional Chinese medicine acanthopanax senticosus extract pellet contains a large amount of saponin, flavone, polysaccharide and other ingredients, has high viscosity, and is easy to cause coating failure due to the problems of viscosity, bed collapse and the like in the fluidized bed coating process. At present, the method for solving the problems mainly comprises the steps of diluting the coating solution, reducing the spraying speed of the coating solution, or adding a certain amount of anti-sticking agents such as ethanol, talcum powder and the like into the coating solution, but the dilution of the coating solution often causes the reduction of the coating speed, improves the production cost, cannot achieve the ideal coating effect for certain traditional Chinese medicine micro-pills with larger viscosity, and simultaneously, the addition of excessive anti-sticking agents can cause the change of the drug release performance of the micro-pills, thereby causing adverse effects on the drug quality.
Disclosure of Invention
The invention aims to provide a coating method of traditional Chinese medicine pellets, which is used for solving the problems in the prior art. The purpose of the invention is realized by the following technical scheme:
the invention provides a coating method of traditional Chinese medicine pellets, which comprises the following steps: 1) coating a layer of powder layer on the surface of a micropill element pill containing a traditional Chinese medicine extract by using pharmaceutically acceptable auxiliary materials to obtain a micropill a, and 2) coating the micropill a by adopting a fluidized bed coating technology; wherein, the pharmaceutically acceptable auxiliary materials in the powder layer are selected from talcum powder, acrylic resin or calcium stearate, preferably the talcum powder or the acrylic resin, and most preferably the talcum powder;
in the coating method of the traditional Chinese medicine pellet, the mesh number of the talcum powder is 800 meshes or higher, preferably 1000-2000 meshes, and more preferably 1200-2000 meshes; the mesh number of the acrylic resin and/or the calcium stearate is 200 meshes or more.
Further, the amount of the talcum powder in the powder layer is 6-25% of the mass of the traditional Chinese medicine extract, and is preferably 8-10%; the dosage of the acrylic resin is 10-25% of the mass of the traditional Chinese medicine extract, and is preferably 15-25%.
In the coating method of the traditional Chinese medicine pellet, the weight increase of the coating is preferably 2-8%, and more preferably 6-8%.
The coating method of the traditional Chinese medicine pellet comprises the following steps: 1) placing the pellet containing Chinese medicinal extract in fluidized bed pan, drying, adding pharmaceutically acceptable adjuvants, and mixing until a layer of uniform powder layer is formed on the surface of pellet; 2) adding water or water-containing organic solvent into the coating material to obtain coating solution, spraying into fluidized bed, and coating to obtain coated Chinese medicinal pellet. Wherein the coating material can be selected from one or more of hydroxypropyl methylcellulose E3, talcum powder, titanium dioxide, polysorbate, Opadry 03A690067 type or Opadry 80W690000 type; the aqueous organic solvent is preferably an aqueous ethanol solution.
Specifically, in the coating method of the traditional Chinese medicine pellet, the traditional Chinese medicine pellet is a traditional Chinese medicine pellet containing acanthopanax senticosus extract; the acanthopanax extract is prepared by the following method: pulverizing radix Acanthopanacis Senticosi, adding water or aqueous ethanol, heating for extraction, filtering, concentrating the filtrate, and drying;
the pill core of the traditional Chinese medicine pellet is a blank pill core, or a medicine-containing pill core prepared by mixing pharmaceutically acceptable auxiliary materials and a traditional Chinese medicine extract; the blank pellet core can be purchased commercially or prepared by adopting a conventional pelleting technology, and the preparation method of the blank pellet core comprises the following steps: (1) taking one or more of microcrystalline cellulose, starch and lactose as excipient, sieving with 200 mesh sieve, placing into pill forming equipment, and mixing; the pill forming equipment can be selected from common pill making or granulating equipment, such as a centrifugal granulator, an extrusion spheronizer or a side-spraying fluidized bed; (2) adding one or more of dextrin pulp, hydroxypropyl methylcellulose and water as binder to make the material flow into flocculent state to form fine particles; (3) maintaining the material in flocculent state, adding excipient and binder again to slowly grow the particles into the target pellet core.
Further, the traditional Chinese medicine micropill pill can be prepared by the conventional pill forming technology in the field, such as an extrusion rolling method, a centrifugal granulation method, a fluidized bed granulation method and the like; preferably, the pharmaceutical composition is prepared by a fluidized bed granulation method, and specifically comprises the following steps: taking the traditional Chinese medicine extract according to the prescription amount, adding a proper amount of water or hydrous ethanol, and uniformly stirring to prepare a medicine solution; putting the pellet core into fluidized bed pan, and spraying the above medicinal solution to obtain Chinese medicinal pellet.
Preferably, pharmaceutically acceptable auxiliary materials can be further added into the medicine solution, and the pharmaceutically acceptable auxiliary materials are selected from one or more of talcum powder, superfine silica gel powder, lactose, chitosan and microcrystalline cellulose.
The traditional Chinese medicine micropill pill is an uncoated traditional Chinese medicine micropill preparation prepared from a traditional Chinese medicine extract and pharmaceutically acceptable auxiliary materials. The inventor finds in long-term experiments that many traditional Chinese medicine extracts have high viscosity, the prepared traditional Chinese medicine micropill pills are easy to stick during the coating process, the coating solution needs to be diluted to an extremely low concentration (less than 1% or 2%), or a large amount of anti-sticking agent is added to complete the coating only marginally, but the operation brings many problems, for example: the volume of the coating liquid is multiplied due to the lower concentration of the coating liquid, and the coating efficiency is obviously reduced; low pill forming rate by coating, poor formability and the like; for pellet formulations with special release requirements (sustained release, controlled release, etc.), a large amount of anti-sticking agent can also affect the release profile of the drug, causing unpredictable effects on the drug quality.
Through a great deal of research, the inventor finds that a layer of uniform powder layer is coated on the plain pills by adopting specific pharmaceutic adjuvant before fluidized bed coating, can effectively solve the problems of pill adhesion, bed collapse, color spots and the like during coating, and partial research experiments are as follows:
preparation of Chinese medicine micro pill
Preparing an acanthopanax extract: taking RADIX Acanthopanacis Senticosi (collected from the area of iron strength in Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi (Latin name: ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) by Prof. of Songhua university of southwest traffic, crushing into 5mm granules, adding 8 times of deionized water, heating to 80 deg.C, extracting for 4 times, 1.5 hr each time, and mixing extractive solutions; concentrating the combined solution under reduced pressure until the relative density is 1.18-1.20g/mL to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparing a pill core: a commercially available microcrystalline cellulose blank pellet core (Hangzhou high-grade biological nutrition technology Co., Ltd.) with a particle size of 750-850 μm is used.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 45% ethanol solution under stirring until the solid content of the solution is 30%, heating in water bath to 50 deg.C until the extract powder is completely dissolved; (2) adding 8% (relative to extract powder) of microcrystalline cellulose into the completely dissolved liquid medicine, and stirring uniformly. (3) Heating the prepared liquid medicine to 50 ℃ in water bath, and continuously stirring. And (3) putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill containing the acanthopanax senticosus extract.
Selection of auxiliary material types of powder layer
The experimental materials used in this experiment were as follows:
pulvis Talci (1000 mesh, available from Guangxi Longshengmi Talcum development Co., Ltd.), silica gel micropowder (particle size of 20-40nm, available from Anhui Shanhe pharmaceutic adjuvant, Inc.), calcium stearate (80 mesh, available from Shanghai Chang, pharmaceutical adjuvant technology Co., Ltd.), magnesium stearate (200 mesh sieved), available from Anhui Shanhe pharmaceutic adjuvant, Inc.), acrylic resin (100 mesh and 200 mesh, available from Shanghai Chang, pharmaceutical adjuvant technology Co., Ltd.), ethyl cellulose (200 mesh sieved), available from Shanghai Chang, pharmaceutical adjuvant technology Co., Ltd.), microcrystalline cellulose (200 mesh sieved), available from Anhui Shanhe pharmaceutic adjuvant, cellulose acetate phthalate (200 mesh sieved), available from Anhui Shanhe pharmaceutic adjuvant, Zeolite (200 mesh sieved), and povidone (200 mesh sieved, Hydroxypropyl methylcellulose (200 mesh screen, available from Anhui mountain river pharmaceutic adjuvant, Inc.).
Placing the pellets obtained in the first step and the preparation of the traditional Chinese medicine pellets in a fluidized bed coating pot, drying for 10 minutes, scattering the auxiliary materials in the table 1 by using a powder scattering gun, uniformly mixing to coat a layer of uniform fine powder on the surfaces of the pellets, weighing an Opadry 03A690067 type coating premix (Shanghai Carlekang coating technology Co., Ltd.) according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, treating for 2-3 cycles by using a homogenizer, starting a fluidized bed, spraying a coating solution, regulating the flow rate from small to large until the coating is finished, and drying to obtain the traditional Chinese medicine pellets.
TABLE 1 screening of auxiliary Material types for powder layers
Note: the dosage percentage of the auxiliary materials is relative to the traditional Chinese medicine extract powder.
The results in table 1 show that, among many common auxiliary materials, only talc powder, calcium stearate and acrylic resin are used, the problem of pellet stickiness can be improved to different degrees, and the yield of the target pellets is high; when talcum powder or acrylic resin is used as a powder layer, the coating process is smoother, the coating duration is shorter, the efficiency is higher, and particularly, the effect of the talcum powder is the best.
Thirdly, selecting the particle size of the auxiliary materials of the powder layer
The experimental materials used in this experiment were as follows:
talcum powder (350 mesh, 800 mesh, 1000 mesh, 1250 mesh, all from Guangxi Longsheng Huamei Talcum development Co., Ltd.), Talcum powder (2000 mesh, from Beijing Phoenix extract medicine and drug component Co., Ltd., Italy Yimi French (IMIFABI)) calcium stearate (from Shanghai Chang, pharmaceutical adjuvant technology Co., Ltd.), acrylic resin (from Shanghai Chang, pharmaceutical adjuvant technology Co., Ltd.)
Placing the pellets obtained in the first step and the preparation of the traditional Chinese medicine pellets in a fluidized bed coating pot, drying for 10 minutes, scattering the auxiliary materials in the table 2 by using a powder scattering gun, uniformly mixing to coat a layer of uniform fine powder on the surfaces of the pellets, weighing the Opadry 03A690067 type coating premix according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, treating for 2-3 cycles by a homogenizer, starting the fluidized bed, spraying coating liquid, regulating the flow rate from small to large until the coating is finished, and drying to obtain the traditional Chinese medicine pellets. .
TABLE 2 particle size screening of powder bed adjuvants
Note: the dosage percentage of the auxiliary materials is relative to the traditional Chinese medicine extract powder.
The results in table 2 show that when the particle size of the talcum powder is 325 meshes, the obtained coated pellets are adhered more, the number of times of bed collapse is more, the yield of the target pellets is low, the coating process is not smooth, the duration is longer, when the particle size of the talcum powder is more than 800 meshes, the obtained pellets have round appearance, the phenomenon of pill adhesion is obviously improved, the coating process is smooth, the coating duration is obviously shortened, and the yield of the target pellets is obviously improved; when the particle size of the talcum powder is more than 1000 meshes, particularly more than 1200 meshes, the pellet has round appearance, no color spot or sticky pellet, the yield reaches more than 90 percent, the coating process is smooth, and the coating duration is greatly shortened.
In addition, when the acrylic resin is 200 meshes or more, the coated pellet has the advantages of round appearance, no color spots, no sticky pellets, smooth coating and higher yield.
Fourthly, selecting the dosage of auxiliary materials of the powder layer
The experimental materials used in this experiment were as follows:
talcum powder (1250 mesh, from Guangxi Longsheng Huamei Talcum development Co., Ltd.), acrylic resin (from Shanghai Chang as pharmaceutical adjuvant technology Co., Ltd.)
Placing the pellets obtained in the first step and the preparation of the traditional Chinese medicine pellets in a fluidized bed coating pot, drying for 10 minutes, scattering auxiliary materials with the dosage shown in the tables 3-1 and 3-2 by using a powder scattering gun, uniformly mixing to coat a layer of uniform fine powder on the surfaces of the pellets, weighing the Opadry 03A690067 type coating premix according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, treating for 2-3 cycles by using a homogenizer, starting a fluidized bed, spraying coating liquid, regulating the flow rate from small to large until the coating is finished, and drying to obtain the traditional Chinese medicine pellets.
TABLE 3-1 powder bed adjuvant dosage Screen
Note: the dosage of the auxiliary materials is calculated relative to the extract powder of the traditional Chinese medicine.
TABLE 3-2 powder bed adjuvant dosage Screen
Note: the dosage of the auxiliary materials is calculated relative to the extract powder of the traditional Chinese medicine.
According to the results of tables 3-1 and 3-2, it can be seen that when the amount of talc is 6-25% of the amount of the extract of the Chinese medicinal materials, the coated pellets have good appearance, high yield (> 80%) of the target pellets, smooth coating process, short coating duration, and the best effect when the amount of talc is 8-10%. When the dosage of the acrylic resin is 10-25% of the mass of the traditional Chinese medicine extract, the coated pellet has round appearance, high yield and short coating time, and the effect is better when the dosage is 15-25%.
When the auxiliary material dosage of the powder layer is lower (the dosage of the talcum powder is less than 6 percent or the dosage of the acrylic resin is less than 10 percent), the pellets are sticky and agglomerated to different degrees, the smoothness of the coating process is poor, the pellets are easy to collapse, and even the coating cannot be smoothly finished; when the auxiliary material dosage is too large (> 25%), the pellet appearance color difference is obvious, and the yield is reduced.
Fifth, selection of weight increment of coating
Placing the pellets obtained in the first step and the preparation of the traditional Chinese medicine pellets in a fluidized bed coating pot, drying for 10 minutes, scattering 10% of talcum powder (1250 meshes) by using a powder scattering gun, uniformly mixing to coat a layer of uniform fine powder on the surfaces of the pellets, weighing an Opadry 03A690067 type coating premix according to the theoretical weight increment in the table 4, adding water to prepare a solution with the solid content of 7%, treating for 2-3 cycles by a homogenizer, starting a fluidized bed to spray coating liquid, regulating the flow rate from small to large until the coating is finished, and drying to obtain the traditional Chinese medicine pellets.
And (3) detecting the moisture absorption rate of the coated pellets: and (3) placing the glass dryer with the supersaturated sodium chloride solution at the bottom in a constant-temperature incubator at 25 ℃ for 24 hours, wherein the relative humidity in the dryer is 75%. Weighing 3g of acanthopanax pellets prepared by the coating method, paving the pellets on the bottom of a weighing bottle with constant weight, precisely weighing the pellets, then placing the pellets in the dryer (the weighing bottle cap is opened), placing the pellets in the dryer in a closed manner at 25 ℃ for more than 24 hours, measuring the pellets once every 24 hours until the weight is within 5mg difference, precisely weighing the pellets, and calculating the moisture absorption rate according to the following formula, wherein the results are shown in table 5.
Moisture absorption rate (mass of sample after moisture absorption-mass of sample before moisture absorption)/mass of sample before moisture absorption x 100%
TABLE 4 coating weight gain screening experiment
| Coating weight gain (%) | 2 | 4 | 8 | 16 |
| Pellet appearance | Round and neat appearance | Round and neat appearance | Round and neat appearance | Pellet viscosity |
| Target pellet yield (%) | 91.03 | 90.42 | 86.26 | 33.16 |
| Duration of coating(min) | 56 | 94 | 239 | 372 |
TABLE 5 moisture absorption data for different coated weighting pellets
| Coating weight gain (%) | Sample weighing (g) before experiment | Weighing bottle (g) before experiment | 6d moisture absorption weight gain% |
| 2 | 3.0071 | 28.2739 | 12.14 |
| 4 | 3.0019 | 28.9884 | 8.65 |
| 6 | 3.0021 | 28.2669 | 1.96 |
| 8 | 3.0078 | 28.2140 | 0.64 |
| 16 | 3.0012 | 28.8743 | 0.23 |
The experimental result shows that when the weight of the coating is increased within the range of 2% -8%, the appearance of the coated pellet is round and round, no color spots exist, no adhesion exists, the yield of the target pellet is high, the coating difficulty is gradually increased when the weight of the coating is increased by more than 8%, the pellet adhesion phenomenon is serious when the weight of the coating is increased by more than 16%, the obtained pellet has large color difference, the yield of the target pellet is obviously reduced, and the coating time is obviously increased. Meanwhile, moisture absorption and weight increase experiments of the pellets show that when the weight increase of the coating is lower than 6%, the moisture-proof effect is poor, the pellets have obvious moisture absorption and weight increase after being stored for 6 days under experimental conditions, and according to the guiding principle of a drug moisture absorption test, the drug can be considered to have slight moisture absorption or no moisture absorption when the moisture absorption and weight increase is lower than 2%, so that the selection range of the packaging material is wider, and the pellet has large production potential.
In conclusion, the coating weight increase within the range of 6-8% can realize good coating effect and play a better moisture-proof role.
Sixth, conventional coating mode comparative test
The self-prepared coating powder used in the experiment comprises the following components: hydroxypropyl methylcellulose E3 (available from Shanghai Chang as pharmaceutical adjuvant technology Co., Ltd.) 100 parts, pulvis Talci (1250 mesh available from Guangxi Longshengmei Huamei Talcum development Co., Ltd.) 4 parts, titanium dioxide (available from Beijing Oriental Kaier commercial Co., Ltd.) 1 part, and Tween 80 (available from Dougelon chemical reagent factory, City).
The conventional coating mode comprises the following steps: according to the table 6, a certain amount of coating material (marked by the coating weight of the pellets increased by 6%) is taken, a coating solvent is added to prepare a coating solution with a certain concentration, the coating solution is stirred for more than 45min by a high-speed shearing machine until the coating material is completely dispersed for later use, the acanthopanax pellets obtained in the step one and the step one of the preparation of the traditional Chinese medicine pellets are put into a fluidized bed, the fluidized bed is started, the coating solution starts to be sprayed when the material temperature is higher than 50 ℃, the speed is increased firstly and then is increased till the coating solution is sprayed completely, and the acanthopanax pellets are dried to obtain the acanthopanax coating liquid.
TABLE 6 comparison of different coating methods
According to the results in table 6, under the conventional coating conditions, no good coating effect can be realized by selecting the commercially available opadry coating premixed powder (containing talcum powder) or the self-prepared coating powder added with the anti-sticking agent (talcum powder), the pellets are seriously sticky, the yield is extremely low, and even the coating is interrupted; after the coating method is used, the same coating material is selected, the coating process is smooth, the appearance of the pellet is round and neat, no color difference or color spots exist, the yield of the pellet is obviously improved, and the coating time is obviously shortened.
The inventors also investigated the coating of the pellet by adding a certain proportion of ethanol solution as an anti-sticking agent, but the problems of pellet stickiness, bed collapse, low yield and the like can not be effectively improved, as shown in table 7.
TABLE 7 examination of the Effect of ethanol addition to coating solution
The coating method of the traditional Chinese medicine pellet can be used for coating various traditional Chinese medicine pellets, is particularly suitable for pellets containing traditional Chinese medicine extracts with larger viscosity, can obviously improve the problems of viscosity, bed collapse, color difference, color spots and the like in the fluidized bed coating process of the traditional Chinese medicine pellets, has the advantages of high pill forming rate, good formability, simple operation, low production cost, high efficiency and the like, and is suitable for industrial mass production application.
Detailed Description
The invention will now be further described with reference to specific examples, which are provided for illustration only and are not to be construed as limiting the invention.
Example 1
Preparing an acanthopanax extract: pulverizing RADIX Acanthopanacis Senticosi (collected from the Yichun region of Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi by Prof. Songhiangchi of southwest traffic university, with Latin name of ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) into granules, adding 8 times of 28% ethanol, heating to boil, extracting for 2 times, 1 hr each time, and mixing extractive solutions; mixing, concentrating under reduced pressure to relative density of 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparation of the pellet core: taking a proper amount of corn starch, and sieving the corn starch by a 200-mesh sieve; weighing 2% (relative to the amount of corn starch) of hydroxypropyl methylcellulose E5 as a binder, and adding water to prepare a 1% binder solution; putting a part of starch into a centrifugal granulator (Chongqing multi-functional centrifugal granulator, model CGC-350), and spraying an adhesive into a storage bin from a spray head of the centrifugal granulator until fine particles are formed; slowly scattering the residual corn starch into a material bin by using a powder adding gun, spraying an adhesive until the particles slowly grow up and become round, and screening out the pellet cores with certain particle sizes as carriers.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 35% ethanol solution under stirring until the solid content is 25%, heating in water bath to 55 deg.C until the extract powder is completely dissolved; (2) adding 5% (based on extract powder) of pulvis Talci into the completely dissolved medicinal liquid, and stirring. (3) Heating the prepared liquid medicine to 55 ℃ in water bath, and continuously stirring. And (3) putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill plain pill in a fluidized bed for 10 minutes, scattering 8% (relative to the extract powder) of talcum powder (1250 meshes, purchased from Guangxi Longsheng Huamei talcum powder development Co., Ltd.) by using a powder scattering gun, and uniformly mixing in the fluidized bed to obtain a micropill a;
preparing a coating layer: (1) preparing a coating solution: hydroxypropyl methyl cellulose E390 parts, talcum powder 3 parts, titanium dioxide 1 parts and polysorbate 801 parts, wherein the above materials are uniformly mixed, the mixed coating powder is weighed according to the theoretical weight increment of 5%, water is added to prepare a solution with the solid content of 7%, and the solution is treated by a homogenizer for 2-3 cycles; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 48 ℃, spraying the prepared coating solution by a spray gun of a bottom spraying or side spraying fluidized bed (multifunctional fluidized bed granulation coating machine, WBF-3G, Chongqing English) until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated traditional Chinese medicine pellet has round appearance and extremely individual visible color difference; yield of the target pellet: 90.32 percent; coating difficulty of the pellets: the whole is smooth; the coating duration was 97 min.
Example 2
Preparing an acanthopanax extract: pulverizing RADIX Acanthopanacis Senticosi (collected from the Yichun region of Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi by Prof. Songhiangchi of southwest traffic university, with Latin name of ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) into granules, adding 8 times of 30% ethanol, heating to boil, extracting for 2 times, 1 hr each time, and mixing extractive solutions; mixing, concentrating under reduced pressure to relative density of 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparation of the pellet core: taking a proper amount of lactose, and sieving by a 200-mesh sieve; 3 percent (relative to the amount of lactose) of hydroxypropyl methylcellulose E5 is weighed as a bonding agent, and water is added to prepare 1 percent bonding agent solution; putting a part of lactose into a centrifugal granulator, and spraying an adhesive into a storage bin from a spray head of the centrifugal granulator until fine particles are formed; and slowly scattering the residual microcrystalline cellulose into a material bin by using a powder adding gun, spraying an adhesive until the particles slowly grow up and become round, and screening out the pellet cores with certain particle sizes as carriers.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 40% ethanol solution while stirring until the solid content of the solution is 30%, heating in water bath to 60 deg.C until the extract powder is completely dissolved; (2) adding 8% (based on extract powder) of pulvis Talci into the completely dissolved medicinal liquid, and stirring. (3) Heating the prepared liquid medicine to 55 ℃ in water bath, and continuously stirring. And (3) putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill pill in a fluidized bed for 10 minutes, scattering 10% (relative to the extract powder) of talcum powder (800 meshes, Guangxi Longsheng Huamei talc development Co., Ltd.) by using a powder scattering gun, and uniformly mixing in the fluidized bed to obtain a micropill a;
preparing a coating layer: (1) preparing a coating solution, namely uniformly mixing 395 parts of hydroxypropyl methyl cellulose E, 5 parts of talcum powder, 1.5 parts of titanium dioxide and 801.5 parts of polysorbate, weighing the mixed coating powder according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, and treating for 2-3 cycles by using a homogenizer; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 43 ℃, spraying the prepared coating solution from a bottom spraying fluidized bed spray gun or a side spraying fluidized bed spray gun until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated Chinese medicinal pellet has round appearance; yield of the target pellet: 80.46 percent; coating difficulty of the pellets: smoothness is realized; the coating duration was 228 min.
Example 3
Preparing an acanthopanax extract: taking RADIX Acanthopanacis Senticosi (collected from the area of iron strength in Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi (Latin name: ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) by Prof. Song Liang of southwest traffic university), crushing into 5mm granules, adding 8 times of deionized water, heating to 80 deg.C, extracting for 4 times, 1.5 hr each time, and mixing extractive solutions; concentrating the combined solution under reduced pressure until the relative density is 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparing a pill core: a commercially available microcrystalline cellulose blank pellet core (Asahi Kasei Co., Ltd., Japan) having a particle size of 750 μm to 850 μm was used.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 45% ethanol solution under stirring until the solid content of the solution is 30%, heating in water bath to 50 deg.C until the extract powder is completely dissolved; (2) adding 8% (calculated by extract powder) of microcrystalline cellulose into the completely dissolved liquid medicine, and uniformly stirring. (3) Heating the prepared liquid medicine to 50 ℃ in water bath, and continuously stirring. And putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill plain pill in a fluidized bed for 10 minutes, scattering 10% (relative to the extract powder amount) of talcum powder (2000 meshes, purchased from Beijing Phoenix extract medicine and medicine component GmbH, Italy Yi-Mi-method ratio (IMIFABI)) by using a powder scattering gun, and uniformly mixing in the fluidized bed to obtain a micropill a;
preparing a coating layer: (1) preparing a coating solution, namely weighing an Opadry 80W690000 type coating premix (Shanghai Carlekang coating technology limited) according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, and treating for 2-3 cycles by using a homogenizer; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 45 ℃, spraying the prepared coating solution from a bottom spraying fluidized bed spray gun or a side spraying fluidized bed spray gun until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated Chinese medicinal pellet has round appearance; yield of the target pellet: 91.23 percent; coating difficulty of the pellets: smoothness is realized; the coating duration is 92 min.
Example 4
Preparing an acanthopanax extract: taking RADIX Acanthopanacis Senticosi (collected from the area of iron strength in Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi (Latin name: ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) by Prof. Song Liang of southwest traffic university), crushing into 8mm granules, adding 8 times of deionized water, heating to 70 deg.C, extracting for 3 times, 1 hr each time, and mixing extractive solutions; concentrating the combined solution under reduced pressure until the relative density is 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparing a pill core: a commercially available sucrose blank pellet core (Shanghai Kalekang coating technology Co., Ltd.) having a particle size of 500 μm to 650 μm was used.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract into 40% ethanol solution while stirring until the solid content of the solution is 35%, heating in water bath to 60 deg.C until the extract powder is completely dissolved; (2) adding 10% (relative to extract powder) of chitosan into the completely dissolved liquid medicine, and stirring uniformly. (3) Heating the prepared liquid medicine to 60 ℃ in water bath, and continuously stirring. And putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill pill in a fluidized bed for 10 min, spraying 7% (relative to the extract powder) of talcum powder (1250 mesh, purchased from Guangxi Longsheng Huamei Talcum development Co., Ltd.) with a powder spraying gun, and mixing uniformly in the fluidized bed to obtain micropill a;
preparing a coating layer: (1) preparing a coating solution, namely weighing an Opadry 03A690067 type coating premix (Shanghai Carlekang coating technology limited) according to the theoretical weight gain of 4%, adding water to prepare a solution with the solid content of 5%, and treating for 2-3 cycles by using a homogenizer; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 45 ℃, spraying the prepared coating solution from a bottom spraying fluidized bed spray gun or a side spraying fluidized bed spray gun until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated Chinese medicinal pellet has round appearance and little color spot; yield of the target pellet: 88.75 percent; coating difficulty of the pellets: smoothness is realized; the coating duration is 114 min.
Example 5
Preparing an acanthopanax extract: taking RADIX Acanthopanacis Senticosi (collected from the area of iron strength of Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi by the Prof of Songhua scientific of southwest traffic university, with the name of latin ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS), crushing into 5mm granules, adding 8 times of deionized water, heating to boil, extracting for 2 times, each time for 0.5 hr, and mixing extractive solutions; concentrating the combined solution under reduced pressure until the relative density is 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparing a pill core: taking a proper amount of microcrystalline cellulose, and sieving to obtain a material with the granularity meeting the requirement; weighing 2% (relative to microcrystalline cellulose) dextrin as binder, adding water to obtain 10% binder solution, heating to 85 deg.C, and gelatinizing; putting a part of microcrystalline cellulose into a side-spraying fluidized bed, and spraying the adhesive into a storage bin from a spray head in the side-spraying fluidized bed until fine particles are formed; and slowly scattering the residual microcrystalline cellulose into a material bin by using a powder adding gun, spraying an adhesive until the particles slowly grow up and become round, and screening out the pellet cores with certain particle sizes as carriers.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 45% ethanol solution while stirring until the solid content of the solution is 30%, heating in water bath to 55 deg.C until the extract powder is completely dissolved; (2) adding 5% (relative to extract powder) of microcrystalline cellulose into the completely dissolved medicinal liquid, and stirring. (3) Heating the prepared liquid medicine to 55 ℃ in water bath, and continuously stirring. And putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill pill in a fluidized bed for 10 min, scattering 8% (of extract powder) of talcum powder (1250 mesh, purchased from Guangxi Longsheng Huamei Talcum development Co., Ltd.) by using a powder scattering gun, and uniformly mixing in the fluidized bed to obtain micropill a;
preparing a coating layer: (1) preparing a coating solution, namely weighing an Opadry 03A690067 type coating premix according to the theoretical weight increment of 5%, adding water to prepare a solution with the solid content of 7%, and treating for 2-3 cycles by using a homogenizer; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 45 ℃, spraying the prepared coating solution from a bottom spraying fluidized bed spray gun or a side spraying fluidized bed spray gun until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated Chinese medicinal pellet has round appearance and no color spot; yield of the target pellet: 90.32 percent; coating difficulty of the pellets: smoothing; the coating duration was 97 min.
Example 6
Preparing an acanthopanax extract: taking RADIX Acanthopanacis Senticosi (collected from the area of iron strength of Yichun city of Heilongjiang province, identified as Chinese medicinal RADIX Acanthopanacis Senticosi (Latin name: ACANTHOPANACANIS SENTICSI RADIX ET RHIZOMA SEU CAULIS) by Prof. of Songhua of southwest traffic university), crushing into 8mm granules, adding 8 times of deionized water, heating to boil, extracting for 2 times, 1 hr each time, and mixing extractive solutions; concentrating the combined solution under reduced pressure until the relative density is 1.18-1.20g/ml to obtain extract; drying the extract liquid to obtain extract powder for later use.
Preparing a blank pill core: taking a proper amount of microcrystalline cellulose, and sieving to obtain a material with the granularity meeting the requirement; 1.5% (with respect to the amount of microcrystalline cellulose) of hydroxypropylmethylcellulose E was weighed3(Shanghai Kalekang coating technology Co., Ltd.) as an adhesive, adding water to prepare a 2% adhesive solution, and fully swelling for more than 12 hours to obtain the adhesive; putting a part of microcrystalline cellulose into a side-spraying fluidized bed, and spraying the adhesive into a storage bin from a spray head in the side-spraying fluidized bed until fine particles are formed; and slowly scattering the residual microcrystalline cellulose into a material bin by using a powder adding gun, spraying an adhesive until the particles slowly grow up and become round, and screening out the pellet cores with certain particle sizes as carriers.
Preparing acanthopanax micropills: (1) gradually adding radix Acanthopanacis Senticosi extract powder into 45% ethanol solution under stirring until the solid content of the solution is 30%, heating in water bath to 50 deg.C until the extract powder is completely dissolved; (2) the completely dissolved liquid medicine is added with 5 percent (calculated by the extract powder) of talcum powder (1250 meshes, Guangxi Longsheng Huamei talc development Co., Ltd.) and evenly mixed. (3) Heating the prepared liquid medicine to 50 ℃ in water bath, and continuously stirring. And putting the pill core into a bottom-spraying or side-spraying fluidized bed, starting to spray the liquid medicine when the temperature of the material is higher than 45 ℃ until the liquid medicine is completely sprayed, and forming the spherical micropill pill.
Preparing a powder layer: drying the spherical micropill essence pill in a fluidized bed for 10 minutes, sprinkling 15% (relative to the extract powder) of acrylic resin (German Rome, Uttch E100, 200 mesh sieve) by using a dusting gun, and uniformly mixing in the fluidized bed to obtain micropill a;
preparing a coating layer: (1) preparing a coating solution, namely weighing an Opadry 80W690000 type coating premix according to the theoretical weight gain of 4%, adding water to prepare a solution with solid content of 5%, and treating for 2-3 cycles by using a homogenizer; (2) and (3) when the temperature of the pellets a in the fluidized bed is higher than 45 ℃, spraying the prepared coating solution from a bottom spraying fluidized bed spray gun or a side spraying fluidized bed spray gun until the coating solution is completely sprayed to form a compact isolation layer, and drying to obtain the pellet coating.
The obtained coated Chinese medicinal pellet has round appearance and small amount of white color spots; yield of the target pellet: 90.16 percent; coating difficulty of the pellets: smoothness is realized; the coating duration is 125 min.
Claims (15)
1. A coating method of traditional Chinese medicine pellets comprises the following steps: 1) coating a layer of powder layer on the surface of a micropill element pill containing a traditional Chinese medicine extract by using pharmaceutically acceptable auxiliary materials to obtain a micropill a, and 2) coating the micropill a by adopting a fluidized bed coating technology to obtain a coated traditional Chinese medicine micropill; wherein, the pharmaceutically acceptable auxiliary materials in the powder layer are selected from talcum powder, acrylic resin or calcium stearate; the mesh number of the talcum powder is 800 meshes or higher; the mesh number of the acrylic resin and/or the calcium stearate is 200 meshes or higher; the amount of the talcum powder in the powder layer is 6-25% of the mass of the traditional Chinese medicine extract; the dosage of the acrylic resin is 10 to 25 percent of the mass of the traditional Chinese medicine extract; the coating weight increment of the traditional Chinese medicine micro-pill is 2 to 8 percent; the traditional Chinese medicine pellet is a traditional Chinese medicine pellet containing acanthopanax senticosus extract.
2. The method for coating Chinese medicinal pellets according to claim 1, wherein the pharmaceutically acceptable auxiliary material in the powder layer is selected from talc or acrylic resin.
3. The method for coating Chinese medicinal pellets according to claim 1, wherein the pharmaceutically acceptable auxiliary material in the powder layer is selected from talc.
4. The method for coating a traditional Chinese medicine pellet as claimed in claim 1, wherein the talc powder has a mesh size of 1000-2000 mesh.
5. The method for coating a traditional Chinese medicine pellet as claimed in claim 4, wherein the talc powder has a mesh size of 1200-2000 mesh.
6. The coating method of the traditional Chinese medicine pellets as claimed in claim 1, wherein the amount of the talcum powder in the powder layer is 8% -10% of the traditional Chinese medicine extract.
7. The coating method of the traditional Chinese medicine pellets of claim 1, wherein the amount of the acrylic resin is 15-25% of the amount of the traditional Chinese medicine extract.
8. The method for coating Chinese medicinal pellets according to claim 1, wherein the weight increase of the coating of the Chinese medicinal pellets is 6-8%.
9. The method for coating the traditional Chinese medicine pellets according to any one of claims 1 to 8, wherein the coating method comprises the following steps: 1) placing the pellet containing Chinese medicinal extract in fluidized bed, drying, adding pharmaceutically acceptable adjuvants, and mixing until a layer of uniform powder layer is formed on the pellet surface; 2) adding water or water-containing organic solvent into the coating material to obtain coating solution, spraying into fluidized bed, and coating to obtain coated Chinese medicinal pellet.
10. The coating method of the traditional Chinese medicine micro-pill according to claim 9, wherein the coating material is selected from one or more of hydroxypropyl methylcellulose E3, talcum powder, titanium dioxide, polysorbate, Opadry 03A690067 type or Opadry 80W690000 type; the aqueous organic solvent is an ethanol aqueous solution.
11. The coating method of the traditional Chinese medicine pellet as claimed in claim 1, wherein the acanthopanax senticosus extract is prepared by the following method: pulverizing radix Acanthopanacis Senticosi, adding water or aqueous ethanol, heating for extraction, filtering, concentrating the filtrate, and drying.
12. The coating method of the traditional Chinese medicine pellets according to claim 1, wherein the pellet core of the traditional Chinese medicine pellets is a blank pellet core, or a drug-containing pellet core prepared by mixing a pharmaceutically acceptable auxiliary material with a traditional Chinese medicine extract; the blank pellet core is purchased commercially or prepared by adopting a conventional pelleting technology, and the preparation method of the blank pellet core comprises the following steps: (1) taking one or more of microcrystalline cellulose, starch and lactose as excipient, sieving with 200 mesh sieve, placing into pill forming equipment, and mixing; the pelleting equipment is selected from a centrifugal granulator, an extrusion spheronizer or a side-spraying fluidized bed; (2) adding one or more of dextrin pulp, hydroxypropyl methylcellulose and water as binder to make the material flow into flocculent state to form fine particles; (3) maintaining the material in flocculent state, adding excipient and binder again to slowly grow the particles into the target pellet core.
13. The coating method of the traditional Chinese medicine pellets according to claim 12, wherein the traditional Chinese medicine pellets are prepared by an extrusion spheronization method, a centrifugal granulation method or a fluidized bed granulation method.
14. The coating method of the traditional Chinese medicine pellets according to claim 13, wherein the traditional Chinese medicine pellets are prepared by a fluidized bed granulation method, and specifically comprise the following steps: taking the traditional Chinese medicine extract according to the prescription amount, adding a proper amount of water or hydrous ethanol, and uniformly stirring to prepare a medicine solution; putting the pellet core into fluidized bed, and spraying the solution to obtain Chinese medicinal pellet.
15. The coating method of the traditional Chinese medicine micro-pill according to claim 14, wherein the solution further comprises pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials are selected from one or more of talcum powder, aerosil, lactose, chitosan and microcrystalline cellulose.
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