CN100415213C - Preparation method of medicinal single layer core osmotic pump tablet - Google Patents
Preparation method of medicinal single layer core osmotic pump tablet Download PDFInfo
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- CN100415213C CN100415213C CNB2005100621563A CN200510062156A CN100415213C CN 100415213 C CN100415213 C CN 100415213C CN B2005100621563 A CNB2005100621563 A CN B2005100621563A CN 200510062156 A CN200510062156 A CN 200510062156A CN 100415213 C CN100415213 C CN 100415213C
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Abstract
The present invention discloses a preparation method for single layer core osmotic pump tablets, which comprises the following steps: 1), uniformly mixing medicines with a penetrating agent, a thickening agent and a filling agent which are sieved by a 100-mesh sieve, adding adhesive for preparing soft materials and granules, adding a lubricating agent after drying and granulation, and pressing to obtain single layer tablet cores with concave holes by a tabletting machine; 2), dissolving semipermeable macromolecular materials, a plasticizing agent and a permeation rate regulating agent in solvent to obtain coating solution; using the coating solution for coating the single layer tablet cores with concave holes in a coating pan to obtain coated tablets; putting the coated tablets into a baking oven, and removing residual solvent by drying to obtain osmotic pump tablets. The osmotic pump tablets prepared by the present invention can approach to zero level release medicines. The method has the advantages that the necessary punching process after the coating process in the process of producing the existing osmotic pump tablet can be saved, and expensive laser punching machines are saved; therefore, the method also has the advantages of technology simplification, cost reduction and benefit to industrialization.
Description
Technical field
The present invention relates to medical manufacturing technology field, relate in particular to a kind of preparation method of single layer core osmotic pump tablet of medicine.
Background technology
Rajan K Verma, Divi Murali Krishna and Sanjay Garg (Journal ofControlled Release, 2000 (79): 7-27), and Giancarlo Santus and Richard WBaker (Journal of Controlled Release, 1995,35:1-21) more detailed summary has been done in the principle and the evolution of osmotic pump tablet.(Acta Pharmaceutica Sinica, 2003,38 (12): 966-967) sustained release that single layer core osmotic pump tablet is used for insoluble drug was done the research report to Liu Longxiao etc.Zhuan Yue etc. (practical drug preparation technique, Beijing: People's Health Publisher, 1999) introduce tablet machine.
Osmotic pump controlled release tablet directly utilizes permeable pressure head for the dynamic Control medicine at the uniform velocity discharges, and is optimal up to now a kind of controlled release formulations for oral administration, has many advantages, such as, (1) at the uniform velocity discharges medicine, and it is stable to keep blood drug level, reduces poisonous side effect of medicine; (2) long action time is realized administration once a day, reduces the inconvenience of frequent drug administration; (3) consistent in the body with external release result, be not subjected to the influence of intestines and stomach acidity and wriggling thereof; 4) economic worth is high.
Common single layer core osmotic pump tablet (primary osmotic pump) generally is made of water soluble drug label, semipermeable polymer coating and drug release hole.When with after water contacts, water sees through coating through diffusion and enters its inside, and the dissolving label generates drug solution, produces inside and outside permeable pressure head thereupon.Under the driving of permeable pressure head, coated its inner static pressure that produces that constantly enters of water.This static pressure makes drug solution outwards discharge from drug release hole.Because the dissolution velocity of medicine is far longer than the seepage velocity of water, its inner solution concentration is constant to be the saturation solubility of medicine.The inside and outside permeable pressure head of osmotic pump tablet is basicly stable, and drug release at the uniform velocity carries out, and dissolves disappearance fully until its inner solid-state drug, during the only remaining shell that includes drug solution till.Coating had both been controlled the penetration speed of water, kept the shape of osmotic pump tablet again.
Be insoluble in water in the existing chemical medicine more than 1/3.The infiltration that these medicines self produce is forced down, and can solve the osmotic pressure problem though add penetrating agent, and solid-state drug powder is tending towards downward sedimentation, can't control its release with common single layer core osmotic pump tablet principle.In label, introduce thickening agent and improved the single layer core osmotic pump tablet obedience infiltration-suspension combined effect sustained release principle that makes, can be used for the sustained release of insoluble drug.
The general laser-beam drilling machine that adopts in the existing osmotic pump tablet commercial production.But laser-beam drilling machine costs an arm and a leg, and every of import was costed 1,000,000 dollars, millions of yuans of home-made also need, and in addition, the performance of homemade punch device is still needed perfect, and punching speed waits to improve.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of single layer core osmotic pump tablet of medicine.
A kind of step of preparation method of single layer core osmotic pump tablet of medicine is:
1) with 1～1000 part of medicine and 1～1500 part of penetrating agent, 1～1500 part of thickening agent and 0.1～200 part of filler mix homogeneously of crossing 100 mesh sieves, add 0.1～50 part of binding agent system soft material, crossing 16 mesh sieves granulates, 55～65 degree oven dry in baking oven, with 14 mesh sieve granulate, add lubricant, suppress the band shrinkage pool monolayer label of hardness 40～120N with tablet machine;
2) 10～100 parts of semipermeable polymer materials, 10～40 parts of plasticizers, 10～40 parts of permeability regulators are dissolved in 1000 parts of solvents and make coating solution.In coating pan the monolayer label coating of above-mentioned band shrinkage pool is made coated tablet with coating solution, coating thickness is 50～300 microns.Coated tablet is put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.
3) also can wrap the water miscible film-coat protective layer of one deck again in the outside of semi permeability coating.
The step of the preparation method of the single layer core osmotic pump tablet of another kind of medicine is:
1) 1～1500 part of penetrating agent, 1～1500 part of thickening agent, 0.1～200 part of filler, 0.1～50 part of binding agent, 0.1～30 part of mix lubricant with 1～1000 part of medicine and mistake 100 mesh sieves is even, makes the monolayer label of the band shrinkage pool of hardness 40～120N with the dry method direct compression with tablet machine;
2) 10～100 parts of semipermeable polymer materials, 0.1～40 part of plasticizer, 0.1～40 part of permeability regulator are dissolved in 1000 parts of solvents and make coating solution.In coating pan the monolayer label coating of above-mentioned band shrinkage pool is made coated tablet with coating solution, coating thickness is 50～300 microns.Coated tablet is put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.
3) also can wrap the water miscible film-coat protective layer of one deck again in the outside of semi permeability coating.
The present invention merges compressed cores and two processes of punching becomes a process, removes the punching process behind the coating from.In the coating process,, but still leave the gap though the shrinkage pool position on the label is partly covered.This gap is the drug release hole of osmotic pump tablet.The present invention can be used for water soluble drug, also can be used for insoluble drug.
Advantage of the present invention:
1) the present invention has removed punching process and the laser-beam drilling machine behind the coating from, has both simplified technology, reduces cost again, is very beneficial for suitability for industrialized production;
2) osmotic pump tablet of utilization the present invention preparation can overcome the shortcoming that ordinary preparation is taken often, blood concentration fluctuation is big, reaches and takes 1 every day, keeps the stable effect of blood drug level.
Description of drawings
Fig. 1 is the structural representation of the upper punch of tablet machine of the present invention;
Fig. 2 is the forward and backward structural representation of band shrinkage pool monolayer label coating of the present invention;
Fig. 3 is the external release curve synoptic diagram of the atenolol osmotic pump tablet made of the present invention.
The specific embodiment
The step of preparation method of the present invention is:
1) with 1～1000 part of medicine and 1～1500 part of penetrating agent, 1～1500 part of thickening agent and 0.1～200 part of filler mix homogeneously of crossing 100 mesh sieves, add 0.1～50 part of binding agent system soft material, crossing 16 mesh sieves granulates, 55～65 degree oven dry in baking oven, with 14 mesh sieve granulate, add lubricant, suppress the band shrinkage pool monolayer label of hardness 40～120N with tablet machine;
2) 10～100 parts of semipermeable polymer materials, 0.1～40 part of plasticizer, 0.1～40 part of permeability regulator are dissolved in 1000 parts of solvents and make coating solution.In coating pan the monolayer label coating of above-mentioned band shrinkage pool is made coated tablet with coating solution, coating thickness is 50～300 microns.Coated tablet is put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.
3) also can wrap the water miscible film-coat protective layer of one deck again in the outside of semi permeability coating.
The monolayer label includes medicine, penetrating agent, thickening agent, filler, binding agent and lubricant, and described medicine is chemical medicine or Chinese medicine monomer, water soluble or be insoluble in water; Penetrating agent is salt or sugar; Thickening agent is polyethylene glycol oxide, polyvinylpyrrolidone, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose or hydroxyethyl-cellulose; Filler is lactose, sucrose, starch, mannitol or microcrystalline Cellulose; Binding agent is polyvinylpyrrolidone, dextrin, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose or the polyethylene glycol oxide solution in water or alcohol; Lubricant is magnesium stearate, calcium stearate or Pulvis Talci.
Consisting of of monolayer label:
1～1000 part of medicine;
1～1500 part of penetrating agent;
1～1500 part of thickening agent;
0.1～200 part of filler;
0.1～50 part of binding agent;
0.1～30 part of lubricant.
Coating is sprayed to by coating solution that drying forms on the monolayer label, and coating solution contains semipermeable polymer material, plasticizer, permeability regulator and solvent.Described semipermeable polymer material is one or more of cellulose acetate, ethyl cellulose, cellulose acetate-phthalate or (methyl) acrylic acid (copolymerization) resin; The plasticizer that coating is used is Polyethylene Glycol, triacetyl glycerine or phthalic acid ester; Coating is Polyethylene Glycol, triacetyl glycerine, hydroxypropyl emthylcellulose or salt with the permeability regulator, and the solvent that coating is used is organic solvent or water.
Consisting of of coating solution:
10～100 parts of semipermeable polymer materials;
0.1～40 part of plasticizer;
0.1～40 part of permeability regulator;
1000 parts of solvents.
With insoluble drug atenolol 25.0g and the sodium chloride 100.0g that crosses 100 mesh sieves, polyethylene glycol oxide 125g, behind the mix homogeneously such as starch 7.0g, aqueous solution system soft material with 10% polyethylene glycol oxide, cross 16 mesh sieves and granulate, put into baking oven under 60 degree through 24 hours dryings, again through 14 mesh sieve granulate, add 1% magnesium stearate, be pressed into the label that has diameter 1.2mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing ethyl cellulose 25.0g, Polyethylene Glycol 8.3g dissolves in 95% ethanol of 1000mL and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 180～200 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.By " 2005 editions regulations of Chinese pharmacopoeia are measured the release in vitro degree of medicine, obtain release curve chart 3.As seen from Figure 3, made osmotic pump tablet can discharge atenolol more evenly in reaching 24 hours scope.
With insoluble drug nifedipine 30.0g and the potassium chloride 90.0g that crosses 100 mesh sieves, polyethylene glycol oxide 90.0g, hydroxypropyl emthylcellulose 20.0g, starch 15.0g, microcrystalline Cellulose 20.0g, behind the sucrose 5.0g mix homogeneously,, cross 16 mesh sieves and granulate with the alcoholic solution system soft material of 15% polyvinylpyrrolidone, put into baking oven 60 the degree under through 24 hours dryings, through 14 mesh sieve granulate, add 1% calcium stearate again, be pressed into the label that has diameter 1.2mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing cellulose acetate 25.0g, Polyethylene Glycol 8.7g, glyceryl triacetate 1.3g dissolves in the acetone of 1000mL and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge nifedipine more evenly in reaching 24 hours scope.
With insoluble drug minipress 2.5g and the sodium chloride 80.0g that crosses 100 mesh sieves, polyethylene glycol oxide 120.0g, starch 7.0g, behind the lactose 5.0g mix homogeneously,, cross 16 mesh sieves and granulate with the alcoholic solution system soft material of 15% polyvinylpyrrolidone, put into baking oven 60 the degree under through 24 hours dryings, through 14 mesh sieve granulate, add 1% magnesium stearate again, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing ethyl cellulose 25.0g, hydroxypropyl emthylcellulose 4.0g, Polyethylene Glycol 3.5g dissolves in 95% ethanol of 1000mL and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 120～130 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge minipress more evenly in reaching 24 hours scope.
Embodiment 4
With insoluble drug glipizide 5g and the sodium chloride 85g that crosses 100 mesh sieves, polyethylene glycol oxide 95.0g, sodium carboxymethyl cellulose 20g, starch 10.0g, microcrystalline Cellulose 2.0g, behind the mannitol 15.0g mix homogeneously,, cross 16 mesh sieves and granulate with the alcoholic solution system soft material of 15% polyvinylpyrrolidone, put into baking oven 60 the degree under through 24 hours dryings, through 14 mesh sieve granulate, add 1% Pulvis Talci again, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing ethyl cellulose 25.0g, cellulose acetate-phthalate 2.0g, Polyethylene Glycol 8.0g dissolve in the 1000mL acetone and make coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge glipizide more evenly in reaching 24 hours scope.
With slightly solubility Chinese medicine monomer oleanolic acid 30.0g and the sodium chloride 60.0g that crosses 100 mesh sieves, sucrose 30.0g, lactose 40.0g, mannitol 20.0g, hydroxyethyl-cellulose 45.0g, polyethylene glycol oxide 40.0g is behind the mix homogeneously, aqueous solution system soft material with dextrin, cross 16 mesh sieves and granulate, put into baking oven under 60 degree through 24 hours dryings, again through 14 mesh sieve granulate, add 1% magnesium stearate, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing cellulose acetate 20.0g, Polyethylene Glycol 8.0g, glyceryl triacetate 2.0g dissolves among the acetone 1000mL and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet gets and can discharge oleanolic acid more evenly in reaching 24 hours scope.
Embodiment 6
With slightly solubility Chinese medicine monomer puerarin 50.0g and the sodium chloride 80.0g that crosses 100 mesh sieves, lactose 15.0g, polyethylene glycol oxide 30.0g, hydroxypropyl emthylcellulose 50.0g is behind the microcrystalline Cellulose 30.0g mix homogeneously, alcoholic solution system soft material with 15% polyvinylpyrrolidone, cross 16 mesh sieves and granulate, put into baking oven under 60 degree through 24 hours dryings, again through 14 mesh sieve granulate, add 1% magnesium stearate, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 30～50N.
Take by weighing cellulose acetate 25.0g, Polyethylene Glycol 9.0g, glyceryl triacetate 1g dissolves in the 1000mL acetone and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge puerarin more evenly in reaching 24 hours scope.
Embodiment 7
With water soluble drug sinomenine hydrochloride 120g and the sodium chloride 60g that crosses 100 mesh sieves, polyvinylpyrrolidone 60g, behind the mix homogeneously such as mannitol 7.0g, alcoholic solution system soft material with 15% polyvinylpyrrolidone, cross 16 mesh sieves and granulate, put into baking oven under 60 degree through 24 hours dryings, again through 14 mesh sieve granulate, add 1% magnesium stearate, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 90～110N.
Take by weighing acrylate copolymer Eudragit RS100 20g, Eudragit RL100 5g, Polyethylene Glycol 2.0g, sodium chloride 1.0g dissolve in 95% ethanol of 1000mL and make coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge sinomenine hydrochloride more evenly in reaching 24 hours scope.
Embodiment 8
With water soluble drug sinomenine hydrochloride 120g and the sodium chloride 60g that crosses 100 mesh sieves, polyvinylpyrrolidone 60g, behind the mix homogeneously such as mannitol 7.0g, alcoholic solution system soft material with 15% polyvinylpyrrolidone, cross 16 mesh sieves and granulate, put into baking oven under 60 degree through 24 hours dryings, again through 14 mesh sieve granulate, add 1% magnesium stearate, be pressed into the label that has diameter 0.8mm shrinkage pool of 1000 hardness 90～110N.
Take by weighing cellulose acetate 25.0g, Polyethylene Glycol 9.0g, glyceryl triacetate 1g dissolves in the 1000mL acetone and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge sinomenine hydrochloride more evenly in reaching 24 hours scope.
Embodiment 9
With water soluble drug potassium chloride 250.0g and the sucrose 5.0g that crosses 100 mesh sieves, microcrystalline Cellulose 20.0g, behind the magnesium stearate 3mg mix homogeneously, the dry method direct compression is made the label that has diameter 0.8mm shrinkage pool of 1000 hardness 90～11050N.
Take by weighing cellulose acetate 20.0g, cellulose acetate-phthalate 5.0g, Polyethylene Glycol 9.0g, phthalic acid ester 1.0g dissolves in the 1000mL acetone and makes coating solution.In coating pan, label is carried out coating, make coating thickness reach 160～180 microns with coating solution.Put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.Made osmotic pump tablet can discharge potassium chloride more evenly in reaching 24 hours scope.
Claims (6)
1. the preparation method of a single layer core osmotic pump tablet is characterized in that, the step of method is:
1) with 1～1000 weight portion medicine and 1～1500 weight portion penetrating agent, 1～1500 weight portion thickening agent and 0.1～200 weight portion filler mix homogeneously of crossing 100 mesh sieves, add 0.1～50 weight portion binding agent system soft material and granulation, 55～65 degree oven dry in baking oven, granulate, add 0.1～30 weight portion lubricant, suppress the band shrinkage pool monolayer label of hardness 40～120N with tablet machine;
2) 10～100 weight portion semipermeable polymer materials, 0.1～40 weight portion plasticizer, 0.1～40 weight portion permeability regulator are dissolved in the 1000 parts by volume solvents and make coating solution, in coating pan, the monolayer label coating of above-mentioned band shrinkage pool is made coated tablet with coating solution, coating thickness is 50～300 microns, coated tablet is put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.
2. the preparation method of the single layer core osmotic pump tablet of a kind of medicine according to claim 1 is characterized in that described medicine is chemical medicine or Chinese medicine monomer, water soluble or be insoluble in water; Penetrating agent is salt or sugar; Thickening agent is polyethylene glycol oxide, polyvinylpyrrolidone, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose or hydroxyethyl-cellulose; Filler is lactose, sucrose, starch, mannitol or microcrystalline Cellulose; Binding agent is polyvinylpyrrolidone, dextrin, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose or the polyethylene glycol oxide solution in water or alcohol; Lubricant is magnesium stearate, calcium stearate or Pulvis Talci; The semipermeable polymer material is one or more of cellulose acetate, ethyl cellulose, cellulose acetate-phthalate or (methyl) acrylic acid (copolymerization) resin; Plasticizer is Polyethylene Glycol, triacetyl glycerine or phthalic acid ester; The permeability regulator is Polyethylene Glycol, triacetyl glycerine, hydroxypropyl emthylcellulose or salt; Solvent is organic solvent or water.
3. the preparation method of the single layer core osmotic pump tablet of a kind of medicine according to claim 1, it is characterized in that having one piece of draw point (2) near the center of upper punch (1) inner concave of described tablet machine or the center, the diameter of draw point is 0.2～3mm, and the length of draw point is 0.2～6mm.
4. the preparation method of the single layer core osmotic pump tablet of a medicine is characterized in that, the step of method is:
1) 1～1500 weight portion penetrating agent, 1～1500 weight portion thickening agent, 0.1～200 weight portion filler, 0.1～50 weight portion binding agent, 0.1～30 weight portion mix lubricant with 1～1000 weight portion medicine and mistake 100 mesh sieves is even, makes the monolayer label of the band shrinkage pool of hardness 40～120N with the dry method direct compression with tablet machine;
2) 10～100 weight portion semipermeable polymer materials, 0.1～40 weight portion plasticizer, 0.1～40 weight portion permeability regulator are dissolved in the 1000 parts by volume solvents and make coating solution.In coating pan the monolayer label coating of above-mentioned band shrinkage pool is made coated tablet with coating solution, coating thickness is 50～300 microns.Coated tablet is put into baking oven, removed Disabled in dry 16～24 hours through 45～50 degree and stay solvent promptly to get osmotic pump tablet.
5. the preparation method of the single layer core osmotic pump tablet of a kind of medicine according to claim 4 is characterized in that described medicine is chemical medicine or Chinese medicine monomer, water soluble or be insoluble in water; Penetrating agent is salt or sugar; Thickening agent is polyethylene glycol oxide, polyvinylpyrrolidone, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose or hydroxyethyl-cellulose; Filler is lactose, sucrose, starch, mannitol or microcrystalline Cellulose; Binding agent is a microcrystalline Cellulose; Lubricant is magnesium stearate, calcium stearate or Pulvis Talci; The semipermeable polymer material is one or more of cellulose acetate, ethyl cellulose, cellulose acetate-phthalate or (methyl) acrylic acid (copolymerization) resin; Plasticizer is Polyethylene Glycol, triacetyl glycerine or phthalic acid ester; The permeability regulator is Polyethylene Glycol, triacetyl glycerine, hydroxypropyl emthylcellulose or salt; Solvent is organic solvent or water.
6. the preparation method of the single layer core osmotic pump tablet of a kind of medicine according to claim 4, it is characterized in that having one piece of draw point (2) near the center of upper punch (1) inner concave of described tablet machine or the center, the diameter of draw point is in 0.2～3mm, and the length of draw point is 0.2～6mm.
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| CN101152158B (en) * | 2007-08-21 | 2010-05-26 | 浙江大学 | Method of producing double-layer core permeation pump patch of medicament |
| CN108578380A (en) * | 2017-07-25 | 2018-09-28 | 广州玻思韬控释药业有限公司 | Controlled releasing penetrant pump |
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| 单层芯渗透泵片用于水不溶性药物的控制释放. 刘龙孝等.药学学报，第38卷第12期. 2003 |
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| 口服渗透泵制剂的研究进展. 吴涛等.中国药学杂志，第34卷第2期. 1999 |
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