CN1709223A - Material gradient controlled-release administrating system and its three-dimensional printing-forming preparation method - Google Patents
Material gradient controlled-release administrating system and its three-dimensional printing-forming preparation method Download PDFInfo
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- CN1709223A CN1709223A CN 200510018843 CN200510018843A CN1709223A CN 1709223 A CN1709223 A CN 1709223A CN 200510018843 CN200510018843 CN 200510018843 CN 200510018843 A CN200510018843 A CN 200510018843A CN 1709223 A CN1709223 A CN 1709223A
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Abstract
The present invention relates to an administration system whose release can be controlled by material gradient. Said system is made into the cylindrical form, and is formed from top layer, bottom layer and intermediate layer containing medicine. Said invention also provides the concrete structure of the said every layer, and provides a method for preparing said system by utilizing three-dimensional printing forming technique and its concrete steps.
Description
Technical field
The invention belongs to the medical preparation field, be specifically related to a kind ofly can release material gradient column type controlled-release administrating system and the three-dimensional printing-forming preparation method thereof that the control medicine discharges with relative constant rate of speed that distribute by resistance.
Background technology
By (US patent such as the Sachs of the Massachusetts Institute of Technology, NO.5204055,1993) (Three Dimensional Print, 3DP) forming technique prepares the object with special external form or complex internal structure according to the notion of " successively print, be layering " to the 3 D-printing that at first proposes of people.This technology with the powder be material, the course of processing very flexibly, forming speed is fast, operating cost is low and reliability is high, is one of the most vital new technique in the quick shaping industry.The key equipment of this technology---three-dimensional printer generally is made up of terminal, powder-processed system (comprising powder feed, shop layer and recovery), shower nozzle and adhesive supplying device, precision surface plate and mobile device.
The 3DP forming technique has the height process flexibility of having no precedent on traditional manufacturing industry, and the various tool in need not conventional powder machine-shaping is not subjected to the restriction of any geometry.Because the position of spraying, spraying number of times, spraying rate can arbitrarily be controlled; Different materials can be by different shower nozzle sprayings; Spraying substance can be solution, suspension, emulsion and melt substance etc., so the 3DP forming technique can be controlled local material composition, microstructure and surface characteristic at an easy rate.Simultaneously owing to numerous conventional processes are unified for constantly repeat to bond such process on a machine; be easy to design studies; the problem that in the commercial production conversion process, does not have the technology stability of scale amplification; can save plenty of time and fund, the advantage of real embodiment Rapid Prototyping technique.Compare with other Rapid Prototyping technique, the 3DP forming technique has its unique advantage: compare with the laser selective sintering, device fabrication cost and technology operating cost are all much lower; Compare with fusion sediment, can operate at normal temperatures, move more convenient reliable; Adopt and spray the mode that agglutinating mode has avoided adopting laser or heating and melting, can not influence the activity of active component.Just because of this, the three-dimensional printing-forming technology has just begun various applied researcies in the pharmaceutics field from that time occurring.
As: Wu etc. [J.control.Release, 1996,40 (1): 77-87] at first adopt the 3DP forming technique to carry out the research of drug delivery implant systems produce; Katsta[J.control.Release, 2000 (66): 1-9] and Rowe[J control.Release, 2000 (66): 11-17] etc. usefulness adopts the 3DP forming technique to carry out oral slowly released and controlled-drug delivery system preparation research respectively; WO2000/29202 then discloses a kind of instant collapsing of sucking by the preparation of 3DP forming technique and has released sheet; US 2003/0198677A1 discloses a kind of zero level slowly released and controlled-drug delivery system of the 3DP of utilization forming technique preparation, and this system axial is released with the hydroxypropyl emthylcellulose resistance, radially has the low drug level Gradient distribution of the high circumference in center.At present all kinds of pertinent literature Chinese medicines all is to be written into by the mode of printing liquid, this mode that is written into has its operation and dosage form control one side flexibly, but because the influence of being printed saturation coefficient, limited its medicine printing amount, for addressing this problem, US 2003/0099708 discloses a kind of by printing with suspension improving the method for drug loading, but the raising amount is limited and easily stop up shower nozzle.For how to utilize the 3DP forming technique solve high dose, indissoluble or the preparation of insoluble medicine sustained and controlled release drug-supplying system do not appear in the newspapers both at home and abroad.
Summary of the invention
Problem to be solved by this invention provides a kind ofly can release material gradient column type controlled-release administrating system and the three-dimensional printing-forming preparation method thereof that the control medicine discharges with relative constant rate of speed that distribute by resistance.
Technical scheme provided by the invention is: a kind of material gradient controlled-release administrating system, this system is column type, constitute by top layer, bottom and the intermediate layer of containing medicine, top layer and bottom are formed by insoluble polymer bonding, the intermediate layer of containing medicine play that resistance is released or the density of the controlled-release material of slow releasing function from outside past interior by distribution gradient radially.
Said controlled-release material density from outside refer to outermost material density maximum toward interior by distribution gradient radially, it is the tightest to bond; Innermost layer density of material minimum, it is the loosest to bond.
Said controlled-release material is water-fast medicinal high molecular polymer or hydrophobic wax material; The insoluble polymer of said composition top layer and bottom is ethyl cellulose, vinyl acetate cellulose, polylactic acid or ε-polylactone or acrylic resin.
The ethyl cellulose that said medicinal high molecular polymer is viscosity 3-10cps, hydroxypropyl emthylcellulose, polyvinyl acetate, polylactic acid, poly-Acetic acid, hydroxy-, bimol. cyclic ester, poly-third are handed over Acetic acid, hydroxy-, bimol. cyclic ester, poly-epsilon-caprolactone, acrylic resin or vinyl acetate cellulose; The hydrophobic wax material is hexadecanol, octadecanol, castor oil hydrogenated, stearic acid or Cera Flava.
Said medicine is to acetyl-amino phenol, naproxen, metformin hydrochloride, indomethacin, left fluorine alkali, aspirin, furosemide, levodopa, actarit or helicidum.
The present invention also provides the preparation method of above-mentioned material gradient controlled-release administrating system, adopt the three-dimensional printing-forming technology, be prepared by " successively print, be layering ", top layer and bottom are laid the controlled-release material powder that effect is released in resistance, and the spraying adhesive bonding is shaped; The mixed-powder that contains medicine and excipient is laid in the intermediate layer, and the spraying adhesive bonding is shaped, on each aspect, binding agent difference, spraying rate and/or spraying number of times difference by different zone sprayings constitute aspect controlled release material concentration area differentiation, obtain the Gradient distribution of controlled-release material.
On the same aspect in said intermediate layer, be meant that in different zone spraying number of times differences the spraying number of times is few more gradually from the past center of circle of circumference.
The mixed-powder that the laying of above-mentioned intermediate layer contains medicine and excipient contains following composition by weight: 100 parts of medicines; 10～30 parts of hydroxypropyl emthylcelluloses; 5～20 parts of polyvinylpyrrolidones; 0～2 part of micropowder silica gel.
Said end face and bottom surface spray as binding agent with ethanol that contains corresponding insoluble polymer or aqueous acetone solution and stick into shape; The mixed-powder in intermediate layer sprays with ethanol that contains corresponding insoluble polymer or wax material or aqueous acetone solution and sticks into shape.
Said end face and bottom surface, spray 1 time or the multipass shaping that bonds as binding agent with the ethanol that contains 0～8wt% insoluble polymer or aqueous acetone solution, and wherein ethanol or acetone volume content are 60～100% in ethanol or the aqueous acetone solution; The mixed-powder in intermediate layer with the ethanol of water-fast medicinal high molecular polymer or hydrophobic wax material and polyvinylpyrrolidone or aqueous acetone solution as binding agent, the content of wherein medicinal high molecular polymer or hydrophobic wax material is 1～5wt%, polyvinylpyrrolidone content is 0～10wt%, and ethanol or acetone volume content are 60～100% in ethanol or the aqueous acetone solution.
The present invention adopts technique scheme, releases making medicine only from radially discharging by the resistance of bottom surface, top; Release radially Concentraton gradient distribution of material by resistance, the control medicine is with constant relatively speed release.
In the prepared process of the inventive method, form resistance release the bonding of the powder such as ethyl cellulose of face be shaped can by its coordinative solvent of spraying as: ethanol, acetone etc. are as binding agent.Also can in these solvents, dissolve a certain amount of corresponding powder wiring solution-forming as binding agent.The medicine of mid portion and adjuvant mixed-powder, contain certain density resistance by spraying and release the solution of material and polyvinylpyrrolidone class binding agent as spray coating liquor, then by spray coating liquor and the spraying number of times change, zones of different has different resistances and releases density of material and adhesion strength in the control medicament, therefore can control the erosion rate of zones of different, wherein contained active component can be discharged with relatively stable speed.
The invention provides the three-dimensional printing-forming technology and prepare determining and prioritization scheme of slowly released and controlled-drug delivery system technological parameter.By " dripping test " (binding agent is being dripped to outside the 3 D-printing system on the corresponding powder), bar girdle tests (with 3 D-printing system spraying coating line and band on corresponding powder bed) etc., perusal and relatively bond effect, bonding rate of drying, bonding after strain and contraction, situations such as number of defects, band intensity in the bonding band, determine to optimize interlayer blanking time, powder shop layer thickness, spray rate (spraying drop amount * spraying frequency), shaping preparation technology parameters such as spraying number of times.
The present invention is applicable to insoluble or indissoluble, and dosage requires general or higher medicine, and medicine generally discharges with corrosion mechanism.The hydroxypropyl emthylcellulose of selecting for use in the mixed-powder is a low viscosity series, as: HPMC E50, HPMC E100, HPMC E15 etc.; The resistance that is used to spray is released material and is generally the low viscosity grade product, as 3,5,7, the ethyl cellulose of 10cps, can make spraying process more continuous, more stable like this, and the drug-supplying system quality is higher.
Description of drawings
Fig. 1 prepares controlled-release administrating system technical process sketch map for the three-dimensional printing-forming technology;
Fig. 2 is the structure chart of material gradient controlled-release administrating system of the present invention;
Fig. 3 is the A-A profile of Fig. 2;
Fig. 4 (a) is the environmental scanning electronic microscope figure of material gradient in the drug-supplying system of the present invention (b);
Fig. 5 is for being the drug accumulation release graphics of the slowly released and controlled-drug delivery system of controlled release functionally gradient material (FGM) with the 5cps ethyl cellulose;
Fig. 6 is for being the drug accumulation release graphics of the slowly released and controlled-drug delivery system of controlled release functionally gradient material (FGM) with the hexadecanol.
The specific embodiment
Three-dimensional printing-forming preparation process of the present invention is as shown in Figure 1: utilize area of computer aided (CAD) design controlled-release material gradient drug-supplying system, the drug-supplying system that contains material information model is provided, exchange interface routine by the drug-supplying system model with the forming machine data.Directly control the operation preparation by the terminal output order.The powder feed device of system is transported to pressed powder 1 on the platform 2 earlier, carry out roll extrusion shop layer by shop rod 3, move on X-Y plane by 3 D-printing system drive shower nozzle 4 subsequently, selectively in different regional spraying adhesive 5, with powder bonded together, form the two-dimensional layer sheet.On the Z axle, drive whole decline of powder bed then and determine height (being powder shop layer thickness) by piston rod 6, carrying out new one deck powder shop layer and bonding prints, so repeat, machining 3 D article spray formation is finished up to institute, carries out suitable post processing (as drying, gumming, suitable compression etc.) and promptly gets 3D solid finished product 7.
Prepared material gradient drug-supplying system is shown in Fig. 2,3, and each drug-supplying system is released layer 8, middle medicated layer 9 and bottom resistance by top resistance and released layer 10 and form.Variation by the spraying number of times prepares that radially material gradient is as follows: the big I according to the tablet diameter is divided into 5 zones with tablet garden face, first pass is sprayed on 11,12,13,14 districts, be sprayed on 11,12,13 districts for second time, be sprayed on 11,12 districts the 3rd time, 4th, be sprayed on 11 districts the 5th time, be equivalent to spray 5,3,2,1,0 times toward 11,12,13,14,15 5 interior zones from most peripheral like this, thereby obtain the most peripheral resistance and release the density of material maximum, it is zero Gradient distribution that density of material is released in the center resistance.
Embodiment 1: the allotment of shop layer powder and binding agent
The ethyl cellulose of 5cps is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; Take by weighing 5cps ethyl cellulose powder 2 grams, be dissolved in the ethanol water of 100mL 90%, be mixed with end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
To 100 parts in acetyl-amino phenol
20 parts of hydroxypropyl emthylcellulose HPMC E50
10 parts of polyvinylpyrrolidone K30
Take by weighing 5cps ethyl cellulose powder or hexadecanol 2 grams, polyvinylpyrrolidone K30 powder 5 grams are dissolved in the ethanol water of 100mL 90%, are mixed with corresponding middle pastille mixed-powder shaping binding agent.
Embodiment 2: determine the three-dimensional printing-forming parameter
End face and bottom surface spray formation parameter:
Interlayer interval 3min
Powder shop layer thickness 200 μ m
Spray rate [spraying drop amount (amount of droplets * drop size) * spraying frequency] 4nL * 12kz
Spraying number of times 3 times
Middle pastille mixed-powder spray formation parameter:
Interlayer interval 5min
Powder shop layer thickness 200 μ m
Spray rate (spraying drop amount * spraying frequency)
Spraying number of times 5 times
Embodiment 3: preparation controlled-release material gradient slowly released and controlled-drug delivery system
Directly control the operation preparation by the terminal output order.Spread a layer thickness 200 μ m ethyl cellulose powder earlier, 90% ethanol water of 2 times 2% ethyl celluloses of spraying is shaped as binding agent, is the bottom surface of tablet, and piston rod drives whole decline of powder bed of workbench subsequently, prepares new one deck and spreads powder.
The intermediate layer then is a hydroxypropyl emthylcellulose adjuvant and to the mixed-powder of acetyl-amino phenol; shop layer thickness 200 μ m; with 90% ethanol water that contains 2% ethyl cellulose (or hexadecanol of 2%) and 5% polyvinylpyrrolidone as binding agent; most peripheral spraying 5 times; spray successively from outside to inside 3,2,1,0 times, repeat 30 layers.
Subsequently, repave a layer thickness 200 μ m ethyl cellulose powder, 90% ethanol water of 2 times 2% ethyl celluloses of spraying is shaped as binding agent, is the end face of tablet.At last the gained tablet is carried out drying, gumming promptly.
Embodiment 4: the conventional analysis of controlled-release material gradient slowly released and controlled-drug delivery system and structural analysis experiment
By " inspection of tablet quality standard done in 2005 editions appendix of Chinese pharmacopoeia, and the result shows that hardness, friability all meet the requirements.The same medicine system that sells wholesale carries out the medicament contg inspection, sd=0.036 (n=6), and the different batches drug-supplying system carries out the medicament contg inspection, sd=0.057 (n=6), conformance with standard.
To being that resistance is released in the tablet of material material gradient and agglutinating effect and made environmental scanning electronic microscope and observe with the ethyl cellulose, the result as shown in Figure 4, (a) (b) be the section Electronic Speculum figure of drug-supplying system from the periphery to the center, amplification is followed successively by 300,80 times, (a) tablet peripheral part controlled-release material density of being reflected is big as can be seen, voidage is little, and bonding closely; (b) the nearly central area of the tablet that is reflected, controlled-release material density is more little, and voidage is big, and structure is loose relatively more, presents tangible gradient and reduces.
Embodiment 5: the release experiment that with the 5cps ethyl cellulose is the slowly released and controlled-drug delivery system of controlled release functionally gradient material (FGM)
Simulation human body environment carries out the external dissolution test of medicine, " 2005 editions appendix xC of Chinese Pharmacopoeia, xD transfer basket method are carried out the release test in employing, release conditions: rotating speed (100 ± 1) r/min, temperature (37.5 ± 0.5) ℃, 0～2 hour, hydrochloric acid solution with pH1.2 is a release medium, and the phosphate buffered solution with pH6.8 is a release medium subsequently.The cumulative release curve as shown in Figure 5, the result shows that 98.75% pair of acetyl-amino phenol discharged by zero level in 13 hours, linear regression coeffficient r is 0.9887.
Embodiment 6: the release experiment that with the hexadecanol is the slowly released and controlled-drug delivery system of controlled release functionally gradient material (FGM)
Simulation human body environment carries out the external dissolution test of medicine, " 2005 editions appendix xC of Chinese pharmacopoeia, xD transfer basket method are carried out the release test in employing, release conditions: rotating speed (100 ± 1) r/min, temperature (37.5 ± 0.5) ℃, 0～2 hour, hydrochloric acid solution with pH1.2 is a release medium, and the phosphate buffered solution with pH6.8 is a release medium subsequently.The cumulative release curve as shown in Figure 6, the result shows that 95.78% pair of acetyl-amino phenol discharged by zero level in 9 hours, linear regression coeffficient r is 0.9906.
Embodiment 7: the allotment of shop layer powder and binding agent
The ethyl cellulose of 3cps is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; Take by weighing 5cps ethyl cellulose powder 7 grams, be dissolved in the 100mL ethanol, be mixed with end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
100 parts of helicidums
10 parts of hydroxypropyl emthylcellulose HPMC E100
7 parts of polyvinylpyrrolidone K60
2 parts of micropowder silica gels
Take by weighing 3cps ethyl cellulose powder 5 grams, polyvinylpyrrolidone K30 powder 2 grams are dissolved in the ethanol water of 100mL 65%, are mixed with corresponding middle pastille mixed-powder shaping binding agent.
All the other press embodiment 2,3 operations (only replacing with the corresponding component of replacing), can obtain the similar result with embodiment 4-6.
Embodiment 8: the allotment of shop layer powder and binding agent
The vinyl acetate cellulose is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; Take by weighing vinyl acetate cellulose 7 grams, be dissolved in the aqueous acetone solution of 100mL 95%, be mixed with end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
100 parts of actarits
30 parts of hydroxypropyl emthylcellulose HPMC E15
20 parts of polyvinylpyrrolidone K15
Take by weighing hydroxypropyl emthylcellulose HPMC E15 1 gram, polyvinylpyrrolidone K15 powder 5 grams are dissolved in the ethanol water of 100mL 60%, are mixed with corresponding middle pastille mixed-powder shaping binding agent.
All the other press embodiment 2,3 operations (only replacing with the corresponding component of replacing), can obtain the similar result with embodiment 4-6.
Embodiment 9: the allotment of shop layer powder and binding agent
Acrylic resin is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; With the ethanol water of 100mL 80% as end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
100 parts of indomethacins
30 parts of hydroxypropyl emthylcellulose HPMC E15
20 parts of polyvinylpyrrolidone K15
Take by weighing octadecanol, polyvinylpyrrolidone K15 powder 5 grams and be dissolved in the ethanol water of 100mL 95%, be mixed with corresponding in the middle of pastille mixed-powder shaping binding agent.
All the other press embodiment 2,3 operations (only replacing with the corresponding component of replacing), can obtain the similar result with embodiment 4-6.
Embodiment 10: the allotment of shop layer powder and binding agent
Polylactic acid is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; Take by weighing 7cps ethyl cellulose powder 3 grams, be dissolved in the aqueous acetone solution of 100mL 95%, be mixed with end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
100 parts of metformin hydrochloride
15 parts of hydroxypropyl emthylcellulose HPMC E15
10 parts of polyvinylpyrrolidone K15
Take by weighing stearic acid 3 grams and be dissolved in the ethanol water of 100mL 75%, be mixed with corresponding middle pastille mixed-powder shaping binding agent.
All the other press embodiment 2,3 operations (only replacing with the corresponding component of replacing), can obtain the similar result with embodiment 4-6.
Embodiment 11: the allotment of shop layer powder and binding agent
ε-polylactone is crossed 200 mesh sieves, get particle diameter and be used for end face and shop, bottom surface layer less than the powder of 74 μ m; Take by weighing 5cps ethyl cellulose powder 3 grams, be dissolved in the acetone soln of 100mL 100%, be mixed with end face and bottom surface powder forming binding agent.
The raw material composition and the content (parts by weight) of middle mixed-powder are as follows:
100 parts of naproxens
15 parts of hydroxypropyl emthylcellulose HPMC E15
10 parts of polyvinylpyrrolidone K15
2 parts of micropowder silica gels
Take by weighing vinyl acetate cellulose 3 grams and be dissolved in the aqueous acetone solution of 100mL 90%, be mixed with corresponding middle pastille mixed-powder shaping binding agent.
All the other press embodiment 2,3 operations (only replacing with the corresponding component of replacing), can obtain the similar result with embodiment 4-6.
The present invention substitutes above-mentioned controlled-release material with other water-fast medicinal high molecular polymers or hydrophobic wax material can obtain similar result.
Claims (9)
1. material gradient controlled-release administrating system, it is characterized in that: this system is column type, constitute by top layer, bottom and the intermediate layer of containing medicine, top layer and bottom are formed by insoluble polymer bonding, the intermediate layer of containing medicine play that resistance is released or the density of the controlled-release material of slow releasing function from outside past interior by distribution gradient radially.
2. material gradient controlled-release administrating system according to claim 1 is characterized in that: said controlled-release material density from outside refer to outermost material density maximum toward interior by distribution gradient radially, it is the tightest to bond; Innermost layer density of material minimum, it is the loosest to bond.
3. material gradient controlled-release administrating system according to claim 1 and 2 is characterized in that: said controlled-release material is water-fast medicinal high molecular polymer or hydrophobic wax material; The insoluble polymer of said composition top layer and bottom is ethyl cellulose, vinyl acetate cellulose, polylactic acid or ε-polylactone or acrylic resin; Said medicine is to acetyl-amino phenol, naproxen, metformin hydrochloride, indomethacin, left fluorine alkali, aspirin, furosemide, levodopa, actarit or helicidum.
4. material gradient controlled-release administrating system according to claim 3 is characterized in that: the ethyl cellulose that said medicinal high molecular polymer is viscosity 3-10cps, hydroxypropyl emthylcellulose, polyvinyl acetate, polylactic acid, poly-Acetic acid, hydroxy-, bimol. cyclic ester, poly-third are handed over Acetic acid, hydroxy-, bimol. cyclic ester, poly-epsilon-caprolactone, acrylic resin or vinyl acetate cellulose; The hydrophobic wax material is hexadecanol, octadecanol, castor oil hydrogenated, stearic acid or Cera Flava.
5. the preparation method of the described material gradient controlled-release administrating system of claim 1, it is characterized in that: adopt the three-dimensional printing-forming technology, be prepared by " successively print, be layering ", top layer and bottom are laid the controlled-release material powder that effect is released in resistance, and the spraying adhesive bonding is shaped; The mixed-powder that contains medicine and excipient is laid in the intermediate layer, and the spraying adhesive bonding is shaped, on each aspect, binding agent difference, spraying rate and/or spraying number of times difference by different zone sprayings constitute aspect controlled release material concentration area differentiation, obtain the Gradient distribution of controlled-release material.
6. preparation method according to claim 5 is characterized in that: on the same aspect in said intermediate layer, be meant that in different zone spraying number of times differences the spraying number of times is few more gradually from the past center of circle of circumference.
7. according to claim 5 or 6 described preparation methoies, it is characterized in that: the mixed-powder that the intermediate layer laying contains medicine and excipient contains following composition by weight: 100 parts of medicines; 10～30 parts of hydroxypropyl emthylcelluloses; 5～20 parts of polyvinylpyrrolidones; 0～2 part of micropowder silica gel.
8. according to claim 5 or 6 described preparation methoies, it is characterized in that: said end face and bottom surface spray as binding agent with ethanol that contains corresponding insoluble polymer or aqueous acetone solution and stick into shape; The mixed-powder in intermediate layer sprays with ethanol that contains corresponding insoluble polymer or wax material or aqueous acetone solution and sticks into shape.
9. preparation method according to claim 8, it is characterized in that: end face and bottom surface with the ethanol that contains 0～8wt% insoluble polymer or aqueous acetone solution as binding agent, spray 1 time or the multipass shaping that bonds, wherein ethanol or acetone volume content are 60～100% in ethanol or the aqueous acetone solution; The mixed-powder in intermediate layer with the ethanol of water-fast medicinal high molecular polymer or hydrophobic wax material and polyvinylpyrrolidone or aqueous acetone solution as binding agent, the content of wherein medicinal high molecular polymer or hydrophobic wax material is 1～5wt%, polyvinylpyrrolidone content is 0～10wt%, and ethanol or acetone volume content are 60～100% in ethanol or the aqueous acetone solution.
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| CN114248434A (en) * | 2021-12-22 | 2022-03-29 | 广东药科大学 | 3D printing pharmacy method with controllable release time |
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