CN105687151A - Method for preparing tablet medicine on basis of ink-jet 3D printing technology - Google Patents

Method for preparing tablet medicine on basis of ink-jet 3D printing technology Download PDF

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Publication number
CN105687151A
CN105687151A CN201610162870.8A CN201610162870A CN105687151A CN 105687151 A CN105687151 A CN 105687151A CN 201610162870 A CN201610162870 A CN 201610162870A CN 105687151 A CN105687151 A CN 105687151A
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China
Prior art keywords
medicine
tablet
ink
jet
tablet medicine
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CN201610162870.8A
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Chinese (zh)
Inventor
汪焰恩
王淑志
魏庆华
李欣培
杨明明
柴卫红
王凯
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Northwestern Polytechnical University
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Northwestern Polytechnical University
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Priority to CN201610162870.8A priority Critical patent/CN105687151A/en
Publication of CN105687151A publication Critical patent/CN105687151A/en
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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides a method for preparing tablet medicine on the basis of an ink-jet 3D printing technology. The method comprises the following steps: firstly, carrying out 3D scanning on the medicine, building a three-dimensional model of the medicine, and carrying out hierarchical processing on the model; then, mixing main ingredients and auxiliary materials required for printing the medicine at a certain ratio, and pressing the mixture into medicine powder; finally, evenly spreading the mixed medicine on a forming platform through 3D printing equipment, and spraying one layer of biological adhesive with good biodegradability on each layer of medicine powder. The method controls the ratio of the auxiliary materials and the main ingredients in the medicine powder as well as the kinds and the contents of biological adhesives, and combines with the excellent characteristics of the 3D technology to control the structure, the ingredients and the like of the printed medicine, the effective dispersion speed and gradient of the tablet is quantitatively regulated and controlled, and speed for the main ingredients to enter blood and the effective use ratio of the medicine are changed.

Description

A kind of method preparing tablet medicine based on ink-jet 3D printing technique
Technical field
The present invention relates to tablet medicine preparing technical field, be specially a kind of method preparing tablet medicine based on ink-jet 3D printing technique。
Background technology
The pharmaceutical preparation that Vehicles Collected from Market uses mainly includes several forms such as tablet, oral liquid and capsule, and wherein lamellar medicament occupies very big proportion。It is all the mode adopting batch compacting to produce that traditional handicraft prepares lamellar medicament, and namely for the medicament of same batch, in medicine, the content of main component and adjunct ingredient is all certain。But in actual disease diagnoses, medicament demand is different (such as to same disease by different sufferer crowds, old people and child need the medicine intake more relatively small than adult), therefore it is accomplished by medicine in preparation process, carries out individual character manufacturing。
The Formulation that tablet is suppressed after referring to medicine main component and adjuvant Homogeneous phase mixing, it is one of important dosage form of being most widely used in modern medicines preparation, the existing circle of its outward appearance, also there are (such as ellipse, triangle, the rhombus etc.) of abnormity。Traditional handicraft is prepared the method for tablet medicine and is mainly included the diverse ways such as granulating tabletting process (wet method and dry method), direct powder compression。Adopting traditional handicraft to prepare tablet requirement tabletting material (granule or powder) and have good mobility and good compressibility and good lubricity, to ensure that medicament is prone to molding and bright and clean, this is increasing difficulty prepared by medicine virtually。
When utilizing traditional handicraft to prepare tablet medicine, remove the main component in medicine, generally also can add the adjuvant such as disintegrating agent, binding agent。Disintegrating agent is to make tablet split rapidly the material being broken into fine particle in gastro-intestinal Fluid, except the tablet of slow (controlled) release tablet and some specific use, all should add disintegrating agent in general tablet。Owing to they have very strong water swellability, it is possible to disintegrate the adhesion of tablet, make tablet split from an overall tablet and be broken into many tiny granules, it is achieved the disintegrate of tablet, so the dissolving being advantageous in tablet principal agent and absorption。General conventional disintegrating agent has dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose etc. several。Binding agent is primarily to reinforcing sheet agent medicine gluing power in preparation process, makes not easily to occur in tablet manufacture the phenomenons such as sliver。Conventional binding agent has starch slurry, cellulose derivative, polyvidone, gelatin, syrup etc. several。
Pharmacy procedure is selected variety classes, the binding agent of variable concentrations and the disintegrating agent of variety classes, different content can change medicament disintegrating property in health gastrointestinal, and then speed and the effective rate of utilization of tablet medicine entrance blood can be changed。
3D prints also referred to as " increase material manufacture ", be one based on design data file, by material layer by layer deposition to be configured to the emerging rapid shaping technique of three-dimensional body。Biometric print is Industrial Printing technology to be combined with biomedical technology, and it is huge especially in the application prospect of medical domain at present。And 3D printing technique is combined with pharmaceutical industry and also would is that the great development direction that future biological 3D prints。
Therefore, for overcome traditional handicraft prepare lamellar medicament exist effective rate of utilization low, personalization does not highlight, accurate controlled release can not be realized well, easily there is the deficiency such as sliver, disintegrating tablet in manufacture process, the present invention proposes effective medicated powder and adjuvant as matrix material, sprays the novel 3D of the binding agent method printing medicine on matrix material simultaneously。
Summary of the invention
Current along with the development of 3D printing technique, 3D printing technique is applied to traditional industries and traditional industries are carried out innovation optimizes a kind of trend being increasingly becoming development in science and technology of future。3D printing technique is applied in traditional bio-pharmaceuticals by this invention exactly, thus realizing the effect such as the maximum utilization to medicine and accurate controlled release。
The technical scheme is that
A kind of described method preparing tablet medicine based on ink-jet 3D printing technique, it is characterised in that: comprise the following steps:
Step 1: set up the threedimensional model of tablet medicine, and tablet medicine threedimensional model is uniformly divided into N shell；Tablet medicine threedimensional model after layering is imported the control system of ink-jet 3D printing device；
Step 2: medicated powder needed for preparation printing medicine:
Step 2.1: weigh the main component preparing medicine needs；
Step 2.2: supplementary product kind and the content of medicine needs is prepared in selection；
Step 2.3: main component and the adjuvant mix homogeneously of medicine needs will be prepared, and be pressed into Powdered；
Step 3: according to the sufferer disintegrate needs to medicine, select the binding agent of corresponding kind and concentration；And the binding agent chosen is poured in ink-jet 3D printing device liquid storage cylinder；
Step 4: print medicine:
Step 4.1: according to the tablet medicine threedimensional model after the layering set up in step 1, the medicated powder of one layer of step 2 preparation of uniform spreading on forming worktable；
Step 4.2: spray 1 layer binder on the medicated powder that paving is spilt；
Step 4.3: repeat step 4.1 and 4.2, until N shell tablet medicine threedimensional model all prints complete；
Step 5: medicine printed in step 4 is dried process, obtains the tablet medicine prepared。
Further preferred version, a kind of described method preparing tablet medicine based on ink-jet 3D printing technique, it is characterised in that: the threedimensional model of tablet medicine is by needing the medicine printed to carry out 3-D scanning acquisition。
Further preferred version, a kind of described method preparing tablet medicine based on ink-jet 3D printing technique, it is characterised in that: in step 2.2, adjuvant includes disintegrating agent, and adjuvant adopts solid granulates。
Further preferred version, a kind of described method preparing tablet medicine based on ink-jet 3D printing technique, it is characterised in that: in step 3, liquid adhesive selected by binding agent；Step 4.2 adopt atomized spray mode spray binding agent。
Beneficial effect
The innovative point of the present invention is:
1. different with extent according to sufferer crowd, by changing kind and the content of disintegrating agent and binding agent in tablet, it is achieved the effective rate of dispersion of quantitatively regulating and controlling tablet and gradient, change main component and enter speed and the medicine effective rate of utilization of blood。
2. the present invention utilizes 3D printing technique to prepare tablet medicine, is possible not only to realize personalization prepared by medicine, it is also possible to effective solve to occur when tradition pressing prepares tablet medicine disintegrating tablet, the problem such as loose pieces。
3. the present invention adopts the process spraying binding agent on medicated powder to print medicine, so can tablet medicine more easy-formation, simultaneously mechanical property is better。
Detailed description of the invention
Being described below in detail embodiments of the invention, embodiment is illustrative of, it is intended to is used for explaining the present invention, and is not considered as limiting the invention。
This embodiment selects preparation APC (Aspirin Phenacetin and Caffeine) agent to be example。APC (Aspirin Phenacetin and Caffeine) is mainly used in heating, headache, neuralgia, toothache, menstrual pain, myalgia, arthralgia。It is mainly composed of: every containing aspirin 0.22g, phenacetin 0.15g, caffeine 0.035g。
Concrete enforcement step is:
Step 1: set up the layering three-dimensional CAD model of APC (Aspirin Phenacetin and Caffeine) agent:
Step 1.1: APC (Aspirin Phenacetin and Caffeine) agent is carried out 3-D scanning and derives stl file, imports stl file in CAD software, obtains the three-dimensional CAD model of APC (Aspirin Phenacetin and Caffeine) agent；
Step 1.2: the APC (Aspirin Phenacetin and Caffeine) agent threedimensional model imported in CAD is from top to bottom uniformly divided into 9 layers, obtain the layering three-dimensional CAD model of APC (Aspirin Phenacetin and Caffeine) agent, and the APC (Aspirin Phenacetin and Caffeine) agent threedimensional model after layering is imported the control system of ink-jet 3D printing device。
Step 2: medicated powder needed for preparation printing medicine:
Step 2.1: weigh aspirin 0.22g, phenacetin 0.15g, caffeine 0.035g；
Step 2.2: select low-substituted hydroxypropyl cellulose as disintegrating agent, weigh 0.03g low-substituted hydroxypropyl cellulose；
Step 2.3 is by the aspirin weighed, phenacetin, caffeine and low-substituted hydroxypropyl cellulose mix homogeneously, and is pressed into Powdered。
Step 3: according to the sufferer disintegrate needs to medicine, select the binding agent of corresponding kind and concentration；And the binding agent chosen is poured in ink-jet 3D printing device liquid storage cylinder。This prints the sucrose slurry selecting concentration to be 55% as binding agent, is then poured into by sucrose slurry in the liquid storage cylinder of ink-jet 3D printing device。
Step 4: print medicine:
Step 4.1: according to the APC (Aspirin Phenacetin and Caffeine) agent threedimensional model after the layering set up in step 1, the medicated powder of one layer of step 2 preparation of uniform spreading on forming worktable；
Step 4.2: spray 1 layer binder on the medicated powder that paving is spilt；
Step 4.3: repeat step 4.1 and 4.2, until 9 synusia agent medicine threedimensional models all print complete；
Step 5: medicine printed in step 4 is dried process, makes binding agent better be combined with medicated powder, obtains the tablet medicine prepared。
First medicine is carried out 3-D scanning and sets up the threedimensional model of medicine and model is carried out layered shaping by the present invention, then main component needed for printing medicine and adjuvant is mixed by a certain percentage and is pressed into medicated powder。Finally, by 3D printing device, the medicated powder uniform spreading mixed is sprinkled upon on shaped platform, and on every layer of medicated powder, sprays one layer of biological binding agent with good biodegradability properties。The method controls structure and the composition etc. of printed medicine by controlling the ratio of adjuvant and main component in medicated powder, the species content of biological binding agent and the good characteristic of the modern 3D printing technique of combination, realize effective rate of dispersion and the gradient of quantitatively regulating and controlling tablet, change main component and enter blood flow velocity and medicine effective rate of utilization。
Although above it has been shown and described that embodiments of the invention, it is understandable that, above-described embodiment is illustrative of, being not considered as limiting the invention, above-described embodiment can be changed when without departing from principles of the invention and objective, revises, replace and modification by those of ordinary skill in the art within the scope of the invention。

Claims (4)

1. the method preparing tablet medicine based on ink-jet 3D printing technique, it is characterised in that: comprise the following steps:
Step 1: set up the threedimensional model of tablet medicine, and tablet medicine threedimensional model is uniformly divided into N shell；Tablet medicine threedimensional model after layering is imported the control system of ink-jet 3D printing device；
Step 2: medicated powder needed for preparation printing medicine:
Step 2.1: weigh the main component preparing medicine needs；
Step 2.2: supplementary product kind and the content of medicine needs is prepared in selection；
Step 2.3: main component and the adjuvant mix homogeneously of medicine needs will be prepared, and be pressed into Powdered；
Step 3: according to the sufferer disintegrate needs to medicine, select the binding agent of corresponding kind and concentration；And the binding agent chosen is poured in ink-jet 3D printing device liquid storage cylinder；
Step 4: print medicine:
Step 4.1: according to the tablet medicine threedimensional model after the layering set up in step 1, the medicated powder of one layer of step 2 preparation of uniform spreading on forming worktable；
Step 4.2: spray 1 layer binder on the medicated powder that paving is spilt；
Step 4.3: repeat step 4.1 and 4.2, until N shell tablet medicine threedimensional model all prints complete；
Step 5: medicine printed in step 4 is dried process, obtains the tablet medicine prepared。
2. a kind of method preparing tablet medicine based on ink-jet 3D printing technique according to claim 1, it is characterised in that: the threedimensional model of tablet medicine is by needing the medicine printed to carry out 3-D scanning acquisition。
3. a kind of method preparing tablet medicine based on ink-jet 3D printing technique according to claim 1, it is characterised in that: in step 2.2, adjuvant includes disintegrating agent, and adjuvant adopts solid granulates。
4. a kind of method preparing tablet medicine based on ink-jet 3D printing technique according to claim 1, it is characterised in that: in step 3, liquid adhesive selected by binding agent；Step 4.2 adopt atomized spray mode spray binding agent。
CN201610162870.8A 2016-03-22 2016-03-22 Method for preparing tablet medicine on basis of ink-jet 3D printing technology Pending CN105687151A (en)

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Cited By (9)

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CN106074412A (en) * 2016-07-05 2016-11-09 南方医科大学 A kind of 3D prints Folium Crataegi total flavones dispersible tablet and preparation method thereof
CN106265572A (en) * 2016-09-20 2017-01-04 南方医科大学 A kind of 3D prints licoflavone dispersible tablet and preparation method thereof
CN106265080A (en) * 2016-09-08 2017-01-04 中南大学 3D prints method and the 3D printing medicine shell of medicine
CN106344527A (en) * 2016-09-20 2017-01-25 南方医科大学 3D printing type ginkgo biloba leave extract dispersible tablet and preparation method thereof
CN106511285A (en) * 2016-09-20 2017-03-22 南方医科大学 3D printing breviscapine orally disintegrating tablet and preparation method thereof
CN106511416A (en) * 2016-09-20 2017-03-22 南方医科大学 3D printed radix notoginseng total saponins orally disintegrating tablet and preparation method thereof
CN106727393A (en) * 2016-12-26 2017-05-31 浙江工业大学 A kind of sustained release preparations of ibuprofen containing grid internal structure and preparation method thereof
CN113301888A (en) * 2019-01-18 2021-08-24 默克专利股份有限公司 Method for producing a solid administration form and solid administration form
CN113334762A (en) * 2021-04-29 2021-09-03 上海宝高文化传播有限公司 Efficient recycling method for coffee grounds based on additive manufacturing

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106074412A (en) * 2016-07-05 2016-11-09 南方医科大学 A kind of 3D prints Folium Crataegi total flavones dispersible tablet and preparation method thereof
CN106265080B (en) * 2016-09-08 2019-12-24 中南大学 3D printing method of medicine and 3D printing medicine shell
CN106265080A (en) * 2016-09-08 2017-01-04 中南大学 3D prints method and the 3D printing medicine shell of medicine
CN106344527B (en) * 2016-09-20 2019-06-21 南方医科大学 A kind of 3D printing Bilobanone ester dispersible tablets and preparation method thereof
CN106511285A (en) * 2016-09-20 2017-03-22 南方医科大学 3D printing breviscapine orally disintegrating tablet and preparation method thereof
CN106511416A (en) * 2016-09-20 2017-03-22 南方医科大学 3D printed radix notoginseng total saponins orally disintegrating tablet and preparation method thereof
CN106265572B (en) * 2016-09-20 2019-03-05 南方医科大学 A kind of 3D printing licoflavone dispersible tablet and preparation method thereof
CN106511285B (en) * 2016-09-20 2019-06-21 南方医科大学 A kind of 3D printing Breviscapinun oral disintegrating tablet and preparation method thereof
CN106344527A (en) * 2016-09-20 2017-01-25 南方医科大学 3D printing type ginkgo biloba leave extract dispersible tablet and preparation method thereof
CN106265572A (en) * 2016-09-20 2017-01-04 南方医科大学 A kind of 3D prints licoflavone dispersible tablet and preparation method thereof
CN106727393A (en) * 2016-12-26 2017-05-31 浙江工业大学 A kind of sustained release preparations of ibuprofen containing grid internal structure and preparation method thereof
CN113301888A (en) * 2019-01-18 2021-08-24 默克专利股份有限公司 Method for producing a solid administration form and solid administration form
CN113334762A (en) * 2021-04-29 2021-09-03 上海宝高文化传播有限公司 Efficient recycling method for coffee grounds based on additive manufacturing

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