CN102253173B - Single pond bionic system device and medicine dissolution liquid and evaluation methodology - Google Patents
Single pond bionic system device and medicine dissolution liquid and evaluation methodology Download PDFInfo
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- CN102253173B CN102253173B CN201110098541.9A CN201110098541A CN102253173B CN 102253173 B CN102253173 B CN 102253173B CN 201110098541 A CN201110098541 A CN 201110098541A CN 102253173 B CN102253173 B CN 102253173B
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- medicine dissolution
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- 239000003814 drug Substances 0.000 title claims abstract description 236
- 238000004090 dissolution Methods 0.000 title claims abstract description 156
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- 239000007788 liquid Substances 0.000 title claims abstract description 101
- 238000000034 method Methods 0.000 title claims abstract description 65
- 238000011156 evaluation Methods 0.000 title claims abstract description 21
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- 230000003111 delayed effect Effects 0.000 claims abstract description 99
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- 229940079593 drug Drugs 0.000 claims abstract description 65
- 238000009792 diffusion process Methods 0.000 claims abstract description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 18
- 239000000243 solution Substances 0.000 claims abstract description 15
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- 239000007983 Tris buffer Substances 0.000 claims abstract description 12
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011780 sodium chloride Substances 0.000 claims abstract description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 5
- 229910000162 sodium phosphate Inorganic materials 0.000 claims abstract description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 4
- 239000001110 calcium chloride Substances 0.000 claims abstract description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract description 4
- 230000009261 transgenic effect Effects 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000945 filler Substances 0.000 claims description 13
- 229910001220 stainless steel Inorganic materials 0.000 claims description 13
- 239000010935 stainless steel Substances 0.000 claims description 13
- 239000003463 adsorbent Substances 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 11
- 229910002027 silica gel Inorganic materials 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 10
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 8
- 230000002572 peristaltic effect Effects 0.000 claims description 8
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 239000007943 implant Substances 0.000 claims description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
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- 230000008569 process Effects 0.000 description 26
- KWORUUGOSLYAGD-UHFFFAOYSA-N magnesium 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C.N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-UHFFFAOYSA-N 0.000 description 23
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- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 20
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 4
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 4
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- 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
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- 238000003760 magnetic stirring Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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- 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 2
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- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention provides single pond bionic system device and medicine dissolution liquid and evaluation methodology, described device is mainly made up of medicine dissolution room, pH adjustor, micropore filter and drug diffusion pond；Containing NaCl 7.8894g, D Glucose 9.008g, CaCl2 0.2797g, MgSO in medicine dissolution liquid A every 1000ml solution40.0975g, MES 1.9524g, HCl (1mM) 5.0mL, remaining is water；Containing KCl 0.7977g, KH in medicine dissolution liquid B every 1000ml solution2PO4 0.1198g、NaCl 7.8894g、NaH2PO40.0965g, MES 9.762g, Tris regulation pH value is to 6.8 7.8, and remaining is water；Described device and evaluation methodology can evaluate release and the absorbing rule of delayed release formulation.
Description
Technical field
The present invention relates to a kind of for evaluate pharmaceutical preparation release and cross-film through the device of feature and medicine dissolution liquid with
Drug evaluation method, a kind of single pond bionic system device for evaluating delayed release formulation and medicine dissolution liquid and evaluation side
Method.
Background technology
Existing drug-eluting/absorption dynamic bionic system (license number: ZL 200920098448.6), molten by medicine
Solve room, pH adjusts room and drug diffusion pond composition, dissolution rate and the evaluation of Premeabilisation of cells effect in aids drug body.So
And going deep into along with research, use this existing drug-eluting/absorption dynamic bionic system can not evaluate delayed release formulation: on the one hand,
Delayed release formulation rests on medicine dissolution room not easy disintegrating, it is impossible to simulation preparation travels to the process of intestinal disintegrate, release from stomach, so
Just it is difficult to predict its physiological disposition；On the other hand, pH adjusts room and there is hold-up volume, causes dissolution side, drug diffusion pond to detect
It is detained on the time of medicine, decreased on apparent concentration, be not easy to microdetermination；Additionally, substantial amounts of adjuvant also can be with
Dissolution fluid and enter pipeline, pile up in silica gel tube and cause pipeline blockage so that test can not proceed.
Summary of the invention
The technical problem to be solved is to provide a kind of single pond bionic system dress for evaluating delayed release formulation
Put.
Another technical problem to be solved by this invention be to provide a kind of be applied to above-mentioned for evaluating delayed release formulation
The medicine dissolution liquid of single pond bionic system device.
Another technical problem to be solved by this invention is that providing a kind of applies the above-mentioned list for evaluating delayed release formulation
Pond bionic system device and medicine dissolution liquid evaluate delayed release formulation release and the method for absorbing rule.
For solving above-mentioned technical problem, the technical scheme is that
A kind of single pond bionic system device for evaluating delayed release formulation, mainly by medicine dissolution room, pH adjustor, micropore
Filter and drug diffusion pond composition, be wherein provided with magnetic stir bar bottom medicine dissolution room, medicine dissolution indoor are provided with a load
Medicine device, leaves distance between the magnetic stir bar bottom described medicine carrying device and medicine dissolution room, and stainless steel mesh is placed in this medicine carrying
Above device；In described pH adjustor, implant is non-adsorbent filler；Drug diffusion pond is by supply chamber, receiving chamber and is entrenched in
Biomembrane tissue composition between the two；Described medicine dissolution room, pH adjustor, micropore filter and drug diffusion pond are by internal diameter
The silica gel tube of 1.0mm-2.0mm is sequentially connected with, and is separately respectively equipped with sample introduction at described medicine dissolution room, pH adjustor and receiving chamber
Hole, is additionally provided with air inlet and thief hole at described supply chamber and receiving chamber.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described medicine carrying device is by resistance to strong acid, resistance to
Medicine carrying basket or sheet metal that highly basic, resistant to elevated temperatures stainless steel material are made press from both sides.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described non-adsorbent filler is sea sand
Or glass microsphere.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described micropore filter is replaceable dress
Put.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described micropore filter aperture is 0.22 μ
m-0.8μm。
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described micropore filter is synthetic fibers
Filter membrane, quartz fibre filter membrane or glass fiber filter.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described biomembrane tissue is Caco-2
And transgenic cell monofilm, MDCK and transgenic cell monofilm thereof or animal intestine in vitro.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described Caco-2 transgenic cell bag
Include Caco-2/CYP3A4 transgenic cell, Caco-2/CYP2D6 transgenic cell, Caco-2/CYP2C9 transgenic cell,
Caco-2/CYP2C19 transgenic cell or Caco-2/CYP1A2 transgenic cell.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described Caco-2 transgenic cell is
Caco-2/CYP3A4 transgenic cell.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described MDCK transgenic cell includes
MDCK-CYP3A4 transgenic cell, MDCK-CYP2D6 transgenic cell, MDCK-CYP2C9 transgenic cell, MDCK-
CYP2C19 transgenic cell, MDCK-CYP1A2 transgenic cell, MDCK-MDR1-CYP3A4 transgenic cell, MDCK-MDR1-
CYP2D6 transgenic cell, MDCK-MDR1-CYP2C9 transgenic cell, MDCK-MDR1-CYP2C19 transgenic cell or
MDCK-MDR1-CYP1A2 transgenic cell.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described MDCK transgenic cell is
MDCK-CYP3A4 transgenic cell or MDCK-MDR1-CYP3A4 transgenic cell.
Preferably, above-mentioned single pond bionic system device for evaluating delayed release formulation, described medicine dissolution room, pH adjustor
And drug diffusion pond is made up of clear perspex material.
A kind of medicine dissolution liquid being applied to above-mentioned single pond bionic system device for evaluating delayed release formulation, including medicine
Lysate A and medicine dissolution liquid B, wherein:
Medicine dissolution liquid A is mainly by NaCl, D-Glucose, CaCl2、MgSO4, MES and HCl (1mM) composition, the most often
Containing NaCl 7.8894g, D-Glucose 9.008g, CaCl in 1000ml solution20.2797g、MgSO4 0.0975g、MES
1.9524g, HCl (1mM) 5.0mL, remaining is water；
Medicine dissolution liquid B is mainly by KCl, KH2PO4、NaCl、NaH2PO4, MES and Tris composition, wherein every 1000ml is molten
Containing KCl 0.7977g, KH in liquid2PO4 0.1198g、NaCl 7.8894g、NaH2PO40.0965g, MES 9.762g, Tris
Regulation pH value is to 6.8-7.8, and remaining is water.
I.e. described in table 1 below:
Table 1 medicine dissolution liquid A, medicine dissolution liquid B component and proportioning
* medicine dissolution liquid B Tris is adjusted to 6.8；Medicine dissolution liquid A and medicine dissolution liquid B adds water to 1000mL.
A kind of above-mentioned single pond bionic system device for evaluating delayed release formulation and medicine dissolution liquid is applied to evaluate slowbreak system
Agent release and the method for absorbing rule, concretely comprise the following steps: is joined by preparation during mensuration in the medicine carrying device of medicine dissolution room, first leads to
Enter medicine lysate A, after certain time, switch to medicine dissolution liquid B；By constant flow peristaltic pump by the drug transfer of dissolving extremely
PH adjustor adjusts liquid with pH and mixes, and is transferred to the supply chamber in drug diffusion pond the most further, and constantly through biomembrane group
Knit entrance medicine receiving chamber, respectively from supply chamber and receiving chamber sampling and measuring.
Preferably, single pond bionic system device and medicine dissolution liquid for evaluating delayed release formulation evaluate delayed release formulation release
With the method for absorbing rule, the switching time of described medicine dissolution liquid A and medicine dissolution liquid B is 15-30min.
The invention has the beneficial effects as follows:
Above-mentioned stainless steel mesh in the medicine dissolution room of the single pond bionic system device evaluating delayed release formulation, as
One-level micropore filter, makes the little granule of preparation of adjuvant and not disintegrate completely not flow out, thus prevents in test undissolved
Little granule enters pH adjustor and causes experiment abberation；It is bionical that pH adjustor is used for regulating above-mentioned single pond for evaluating delayed release formulation
The pH value of system and device, fills non-adsorbent filler in it, pH both can have been made to adjust liquid and medicine dissolution liquid is sufficiently mixed, and again might be used
With as two grades of micropore filters, make the little granule of preparation of adjuvant and not disintegrate completely can not flow out pH adjustor, thus avoid medicine
Blocking that thing adjuvant is piled up in silica gel tube and caused and the short grained loss of preparation, so solve the examination caused because of blocking
Test the serious problems that must stop, additionally, decrease the existence of hold-up volume in conventional device, solve the inspection of diffusion cell dissolution side
Measure the problem that the time is detained and apparent concentration reduces of medicine, it is simple to microdetermination；Described micropore filter is as three grades of micropores
Filter so that the medicine being only completely dissolved release just can enter the supply chamber in drug diffusion pond, prevents from not discharging the stream of medicine
Losing, the settled solution obtained can be directly as analyzing liquid；Even if there being a small amount of adjuvant to pile up at micropore filter and result in blockage existing
As, it is also possible to changing the micropore filter that another one is new very easily, test can proceed, meanwhile, according to different medicines
Agent type, can change micropore filter as required, such as, when pharmaceutical preparation is opaque capsule, synthetic fibers can be used thin
Film is filter membrane；When pharmaceutical preparation toughness composition, a small amount of quartz fibre can be used as filter membrane；When pharmaceutical preparation is disintegration-type
Pharmaceutical preparation, for avoiding absorption, can use glass fiber filter, and glass fiber filter can be reused, every time with finishing
Rinse well, cost-effective.
The technical scheme provided from above invention, compared with prior art, the one that the present invention provides is used for commenting
Single pond bionic system device of valency delayed release formulation is a kind of dynamic apparatus continuously, it is possible to simulation preparation travels to the mistake of intestinal from stomach
Journey, overcomes existing bionic system and for evaluating the deficiency of delayed release formulation, it can not be generalized to widely solid preparation；
Decrease pH and adjust the hold-up volume that room exists, solve diffusion cell dissolution side and detect that the time of medicine is detained and apparent concentration
The problem reduced, it is simple to microdetermination.Meanwhile, solve again and remove pH and adjust the blockage problem that excipient substance causes behind room；Should
Device has fully taken into account the dynamic process in human body, the internal gastrointestinal tract conditions of the normal physiological of true simulation people, and can be anti-
Reflect delayed release formulation dissolving in vivo and absorption process, it is possible to evaluate release and the absorbing rule of delayed release formulation.
Accompanying drawing explanation
Fig. 1 is the structural representation of a kind of single pond bionic system device for evaluating delayed release formulation that the present invention provides；
In figure: the 2-pH adjustor 3-supply chamber 4-receiving chamber of 1-medicine dissolution room
5-silica gel tube 6-medicine carrying basket 7-magnetic stir bar 8-stainless steel mesh
9-non-adsorbent filler 10-micropore filter 11-biomembrane tissue
Fig. 2 is another structural representation of a kind of single pond bionic system device for evaluating delayed release formulation that the present invention provides
Figure；
In figure: the 2-pH adjustor 3-supply chamber 4-receiving chamber of 1-medicine dissolution room
5-silica gel tube 6 '-sheet metal folder 7-magnetic stir bar 8-stainless steel mesh
9-non-adsorbent filler 10-micropore filter 11-biomembrane tissue
Fig. 3 is that diclofenac sodium dissolubility is with pH variation diagram；
Fig. 4 is that diclofenac sodium enteric-coated tablets changes with pH in the single pond bionic system device for evaluate delayed release formulation
Release-time graph (n=3)；
Fig. 5 is that diclofenac sodium enteric-coated tablets is in the single pond bionic system device for evaluate delayed release formulation and in paddle method
The comparison (n=3) of Accumulation dissolution-time graph；
Fig. 6 be diclofenac sodium enteric-coated tablets transmitance in the single pond bionic system device for evaluating delayed release formulation-
Time graph (n=3)；
Fig. 7 is that diclofenac sodium enteric-coated tablets accumulation in the single pond bionic system device for evaluating delayed release formulation passes through
Rate-time graph (n=3)；
Fig. 8 is diclofenac sodium enteric-coated tablets FaAnd FdBetween relation curve (n=10)；
Fig. 9 is that magnesium omeprazole dissolubility is with pH variation diagram；
Figure 10 is that magnesium omeprazole enteric coatel tablets change with pH in the single pond bionic system device for evaluate delayed release formulation
Release-time graph (n=3)；
Figure 11 is that magnesium omeprazole enteric coatel tablets and are turning basket in the single pond bionic system device for evaluate delayed release formulation
The comparison (n=3) of the Accumulation dissolution-time graph in method；
Figure 12 be magnesium omeprazole enteric coatel tablets transmitance in the single pond bionic system device for evaluating delayed release formulation-
Time graph (n=3)；
Figure 13 is that the accumulation in the single pond bionic system device for evaluating delayed release formulation of the magnesium omeprazole enteric coatel tablets is saturating
Cross rate-time graph (n=3)；
Figure 14 is magnesium omeprazole enteric coatel tablets FaAnd FdBetween relation curve (n=10)；
Figure 15 is magnesium omeprazole enteric coatel tablets blood concentration-time curves (n=6) in Beagle dog body；
Figure 16 is that the accumulation in the single pond bionic system device for evaluating delayed release formulation of the magnesium omeprazole enteric coatel tablets is saturating
Cross the correlation curve of rate and the body absorption percent of Beagle.
Detailed description of the invention
In order to make those skilled in the art be better understood from technical scheme, below in conjunction with the accompanying drawings and specifically real
Technical scheme of the present invention is described in further detail by mode of executing.
Embodiment 1
As it is shown in figure 1, a kind of single pond bionic system device for evaluating delayed release formulation, mainly by medicine dissolution room 1, pH
Adjustor 2, removable micropore filter 10 and drug diffusion pond composition, described medicine dissolution room 1, pH adjustor 2 and medicine
Diffusion cell is made up of clear perspex material, is wherein provided with magnetic stir bar 7 bottom medicine dissolution room 1, in medicine dissolution room 1
It is provided with a medicine carrying device, between the magnetic stir bar 7 bottom described medicine carrying device and medicine dissolution room 1, leaves distance, stainless steel sift
Net 8 is placed in above this medicine carrying device；In described pH adjustor 2, implant is non-adsorbent filler 9；Drug diffusion pond by supply chamber 3,
Receiving chamber 4 and be entrenched in biomembrane tissue 11 between the two and form；Described medicine dissolution room 1, pH adjustor 2, micropore filter
Device 10 and drug diffusion pond are sequentially connected with by the silica gel tube 5 of internal diameter 1.0mm, at described medicine dissolution room 1, pH adjustor 2 with connect
Receive room 4 and be separately respectively equipped with sample holes, be additionally provided with air inlet and thief hole, wherein said medicine carrying at described supply chamber 3 and receiving chamber 4
Device is the medicine carrying basket 6 being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material, and described non-adsorbent filler 9 is sea
Sand, described micropore filter 10 is synthetic fibers filter membrane, and its aperture is 0.22 μm, and described biomembrane tissue 11 is Caco-2 cell list
Tunic.
Embodiment 2
As it is shown in figure 1, a kind of single pond bionic system device for evaluating delayed release formulation, have and use with described in embodiment 1
In the structure that the single pond bionic system device evaluating delayed release formulation is similar, wherein said medicine dissolution room 1, pH adjustor 2, micropore
Filter 10 and drug diffusion pond are sequentially connected with by the silica gel tube 5 of internal diameter 2.0mm, in described medicine dissolution room 1, pH adjustor 2 and
Receiving chamber 4 is separately respectively equipped with sample holes, is additionally provided with air inlet and thief hole, wherein said load at described supply chamber 3 and receiving chamber 4
Medicine device is the medicine carrying basket 6 being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material, and described non-adsorbent filler 9 is
Glass microsphere, described micropore filter 10 is glass fiber filter, and its aperture is 0.8 μm, and described biomembrane tissue 11 is MDCK-
CYP3A4 transgenic cell monofilm.
Embodiment 3
As it is shown in figure 1, a kind of single pond bionic system device for evaluating delayed release formulation, have and use with described in embodiment 1
In the structure that the single pond bionic system device evaluating delayed release formulation is similar, wherein said medicine dissolution room 1, pH adjustor 2, micropore
Filter 10 and drug diffusion pond are sequentially connected with by the silica gel tube 5 of internal diameter 1.5mm, in described medicine dissolution room 1, pH adjustor 2 and
Receiving chamber 4 is separately respectively equipped with sample holes, is additionally provided with air inlet and thief hole, wherein said load at described supply chamber 3 and receiving chamber 4
Medicine device is the medicine carrying basket 6 being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material, and described non-adsorbent filler 9 is
Sea sand, described micropore filter 10 is quartz fibre filter membrane, and its aperture is 0.57 μm, and described biomembrane tissue 11 is mdck cell list
Tunic.
Embodiment 4
As in figure 2 it is shown, a kind of single pond bionic system device for evaluating delayed release formulation, have and use with described in embodiment 1
In the structure that the single pond bionic system device evaluating delayed release formulation is similar, wherein said medicine dissolution room 1, pH adjustor 2, micropore
Filter 10 and drug diffusion pond are sequentially connected with by the silica gel tube 5 of internal diameter 1.0mm, in described medicine dissolution room 1, pH adjustor 2 and
Receiving chamber 4 is separately respectively equipped with sample holes, is additionally provided with air inlet and thief hole, wherein said load at described supply chamber 3 and receiving chamber 4
Medicine device is the sheet metal folder 6 ' being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material, described non-adsorbent filler
9 is glass microsphere, and described micropore filter 10 is glass fiber filter, and its aperture is 0.65 μm, and described biomembrane tissue 11 is
Caco-2/CYP3A4 transgenic cell monofilm.
Embodiment 5
As it is shown in figure 1, a kind of single pond bionic system device for evaluating delayed release formulation, have and use with described in embodiment 1
In the structure that the single pond bionic system device evaluating delayed release formulation is similar, wherein said medicine dissolution room 1, pH adjustor 2, micropore
Filter 10 and drug diffusion pond are sequentially connected with by the silica gel tube 5 of internal diameter 2.0mm, in described medicine dissolution room 1, pH adjustor 2 and
Receiving chamber 4 is separately respectively equipped with sample holes, is additionally provided with air inlet and thief hole, wherein said load at described supply chamber 3 and receiving chamber 4
Medicine device is the medicine carrying basket 6 being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material, and described non-adsorbent filler 9 is
Glass microsphere, described micropore filter 10 is quartz fibre filter membrane, and its aperture is 0.35 μm, described biomembrane tissue 11 be animal from
Body intestinal tube.
In addition, the biomembrane tissue 11 used by embodiment 1-5 can the most arbitrarily be changed, such as: Caco-2/
CYP2D6 transgenic cell, Caco-2/CYP2C9 transgenic cell, Caco-2/CYP2C19 transgenic cell or Caco-2/
CYP1A2 transgenic cell, MDCK-CYP2D6 transgenic cell, MDCK-CYP2C9 transgenic cell, MDCK-CYP2C19 turn base
Because cell, MDCK-CYP1A2 transgenic cell, MDCK-MDR1-CYP3A4 transgenic cell, MDCK-MDR1-CYP2D6 turn base
Because of cell, MDCK-MDR1-CYP2C9 transgenic cell, MDCK-MDR1-CYP2C19 transgenic cell or MDCK-MDR1-
CYP1A2 transgenic cell.
Embodiment 6
A kind of medicine dissolution liquid being applied to above-mentioned single pond bionic system device, including medicine dissolution liquid A and medicine dissolution
Liquid B, wherein in every 1000ml solution:
Table 2 medicine dissolution liquid A, medicine dissolution liquid B component and proportioning
* medicine dissolution liquid B Tris is adjusted to 6.8.Medicine dissolution liquid A and medicine dissolution liquid B adds water to 1000mL.
Compound method weighs according to conventional means, mixes.
Embodiment 7
A kind of medicine dissolution liquid being applied to above-mentioned single pond bionic system device, including medicine dissolution liquid A and medicine dissolution
Liquid B, wherein in every 1000ml solution:
Table 3 medicine dissolution liquid A, medicine dissolution liquid B component and proportioning
* medicine dissolution liquid B Tris is adjusted to 7.4.Medicine dissolution liquid A and medicine dissolution liquid B adds water to 1000mL.
Compound method weighs according to conventional means, mixes.
Embodiment 8
A kind of medicine dissolution liquid being applied to above-mentioned single pond bionic system device, including medicine dissolution liquid A and medicine dissolution
Liquid B, wherein in every 1000ml solution:
Table 4 medicine dissolution liquid A, medicine dissolution liquid B component and proportioning
* medicine dissolution liquid B Tris is adjusted to 7.8.Medicine dissolution liquid A and medicine dissolution liquid B adds water to 1000mL.
Compound method weighs according to conventional means, mixes.
Embodiment 9
Now as a example by embodiment 5, embodiment 6, sketch the single pond bionic system for evaluating delayed release formulation of the present invention
The specific works process of device:
(1) debugging thermostatic water-circulator bath, constant flow peristaltic pump, magnetic stirring apparatus and program control sample automatic collector；
(2) after system stability works, solid preparation is joined the medicine carrying device of medicine dissolution room 1, is first passed through medicine molten
Solve liquid A (pH 2.0), after 15-30min, switch to medicine dissolution liquid B (pH 6.8-7.8).The whole dissolution of medicine and absorbing
In journey, each solution is maintained at 37 DEG C ± 0.2 DEG C；
(3) medicine constantly discharges under magnetic stir bar 7 stirring action, and the medicine discharged is transferred to by constant flow peristaltic pump
PH adjustor 2 adjusts liquid (pH 6.8) with pH and mixes, and is transferred to supply chamber 3 the most further, and constantly through biomembrane tissue
11 enter medicine receiving chamber 4.
(4) in the supply chamber 3 in drug diffusion pond and receiving chamber 4, testing sample is pumped out by constant flow peristaltic pump respectively, simultaneously by
Program control sample automatic collector collects dissolution side and the sample through side respectively；
(5) sample is analyzed by suitable analytical tool such as UV spectrophotometer, HPLC or LC-MS.
Specific works process and test result see following embodiment.
Embodiment 10
The single pond bionic system device evaluation diclofenac sodium intestinal for evaluating delayed release formulation described in Application Example 5
The release of molten absorbs with cross-film.
(1) debugging of external single pond bionic system
Medicine dissolution liquid A, medicine dissolution liquid B, pH adjust liquid, the preparation of reception liquid is shown in Table 5.
Table 5 solution preparation program
*Medicine dissolution liquid B, pH adjust liquid Tris and are adjusted to 6.8.Medicine dissolution liquid A, medicine dissolution liquid B, pH adjust liquid and add
Water is to 1000mL.
Medicine dissolution liquid A, medicine dissolution liquid B, pH adjust liquid be put in thermostatic water-circulator bath case keep the temperature at 37 DEG C ±
0.5℃；Constant flow peristaltic pump flow velocity is adjusted to 0.5ml/min；Magnetic stirring apparatus is adjusted to " 5 " shelves.
(2), dispensing
After connecting line, adding medicine dissolution liquid A in medicine dissolution room, supply chamber adds medicine dissolution liquid A Yu pH and adjusts
Liquid, receiving chamber adds reception liquid.Single pond bionic system brings into operation, and offers medicine after stable；Diclofenac sodium enteric-coated tablets dispensing one
Sheet (25mg/ sheet), parallel does 3 times.Medicine dissolution room is first passed through medicine dissolution liquid A, switches to medicine dissolution liquid after 0.5 hour
B。
(3), sample is collected
After dispensing, immediately beginning to timing, start program control sample automatic collector, the dissolution side every 10min of sample collects once.
(4), sample determination
HPLC method measures the content of diclofenac sodium in sample.
Chromatographic condition: Waters600E (automatic sampler, deaerates online, quaternary gradient pump, 2487 detectors), chromatograph
Post: Agilent TC-C18 (5 μm, 4.6 × 150mm), flow phase: 0.5% glacial acetic acid-methanol (20-80), flow velocity: 1ml/
Min, detects wavelength: 276nm, column temperature: 25 DEG C, sample size: 10 μ l.
(5), data process
According to this for evaluating single bionic system dissolution side, pond (supply chamber) of delayed release formulation and through side (receiving chamber) number
According to, draw drug release rate-time graph, drug accumulation release-time graph, medicine transmitance-time graph, medicine are tired
Long-pending transmitance-time graph, and compare with the Pharmacopoeia of the People's Republic of China (hereinafter referred to as " pharmacopeia ") (2010 editions two) institute
State the dissolution result of paddle method and this list pond bionic system.With the different releasing theory of corresponding software matching.
(6), result and conclusion
Diclofenac sodium, pKa=4.0, micro dissolution in pure water, dissolve in methanol, ethanol, be slightly soluble in acetone, insoluble
In chloroform, ether, the dissolving situation in buffer salt solution is shown in Fig. 3.
Knowable to accompanying drawing 4, diclofenac sodium enteric-coated tablets does not discharges at sour environment, and with the rising of pH value, medicine starts to release
Put, show that the single pond bionic system device for evaluating delayed release formulation of the present invention can reflect that preparation is discharged by pH value change
The impact of process.
With diclofenac sodium enteric-coated tablets in the single pond bionic system device dissolution for evaluating delayed release formulation of the present invention
The result that the result of side gained paddle method described with " pharmacopeia " draws compares.See accompanying drawing 5.
From the results, it was seen that diclofenac sodium enteric-coated tablets is switched by simulated gastric fluid in " pharmacopeia " described paddle method release medium
After simulated intestinal fluid, medicine discharges rapidly.And medicine is at the single pond bionic system dress for evaluating delayed release formulation of the present invention
Put middle release to embody from stomach (pH 1-2) to the continuous dynamic process of the gradual change of intestinal (pH 6-8), be closer to human gastrointestinal tract
The physiological status of pH change.Additionally, paddle method can only response preparation cumulative release amount in single dissolution medium, and this is used for commenting
Single pond bionic system device of valency delayed release formulation the cumulative release amount of response preparation also can reflect its transient change result, this
Also it is that paddle method is incomparable.
Diclofenac sodium enteric-coated tablets is in the single pond bionic system device for evaluating delayed release formulation of the present invention and paddle method
In Accumulation dissolution result through Model fitting, the results are shown in Table 6.
Table 6 diclofenac sodium enteric-coated tablets is through Model fitting result
From the point of view of degree of fitting, r value, closer to " 1 ", represents the goodness of fit maximum.Diclofenac sodium enteric-coated tablets is in institute of the present invention
State the drug release process in the single pond bionic system device for evaluating delayed release formulation and paddle method through Model fitting, all meet one
Level releasing theory equation, i.e. this medicine are the one-level drug release process of non-constant velocity.Show that this is bionical for the single pond evaluating delayed release formulation
System and device may be used for evaluating the Drug Release Kinetics feature of diclofenac sodium enteric-coated tablets.
By the diclofenac sodium enteric-coated tablets obtained for the single pond bionic system device evaluating delayed release formulation of the present invention
Transmitance-time graph, accumulation transmitance-time graph.See accompanying drawing 6,7.
With diclofenac sodium enteric-coated tablets in the single pond bionic system device dissolution for evaluating delayed release formulation of the present invention
The Accumulation dissolution of side gained carries out non-linear dependencies investigation with the accumulation transmitance through side gained, and result is shown in Fig. 8.
Assume that vitro Drug dissolution feature is equal to internal dissolution feature, and present first order kinetics under sink conditions
Release and first order kinetics pass through, it can be deduced that following relation:
Wherein α=ka/kd, i.e. one-level transmission rates constant is than one-level dissolution rate constant；faIt is that t is when infinity in body
Absorb percent.
Software MATLAB (version4.0) is used to carry out matched curve.Dissolution speed limit type medicine (α is more than 1) will produce " straight
Line style " relevant figure." inverted L shape " relevant figure will be produced through speed limit type medicine (α is less than 1).Speed limit type medicine is mixed through with dissolution
Thing (α approximates 1) will produce " hockey stick type " relevant figure.
It is readily seen from the relativity evaluation result of Fig. 8: dependency r value is 0.9305, more than marginal value 0.8721, relevant
Property is good.And α=0.3438 ＜ 1, for " inverted L shape " relevant figure, one-level transmission rates constant is less than one-level dissolution rate constant.Cause
The evaluation information of this single pond bionic system device offer for evaluating delayed release formulation of the present invention is the most objective reliably, is better than oar
Method.
Embodiment 11
The single pond bionic system device evaluation magnesium omeprazole intestinal for evaluating delayed release formulation described in Application Example 5
The release of molten absorbs with cross-film.
(1), the debugging of external single pond bionic system
Medicine dissolution liquid A medicine dissolution liquid B, pH adjust liquid, the preparation of reception liquid is shown in Table 7.
Table 7 solution preparation program
*Medicine dissolution liquid B, pH adjust liquid Tris and are adjusted to 6.8, receive liquid Tris and are adjusted to 7.4.Medicine dissolution liquid A, medicine
Thing lysate B, pH adjust liquid, reception liquid adds water to 1000mL.
Medicine dissolution liquid A medicine dissolution liquid B, pH adjust liquid, reception liquid is put in thermostatic water-circulator bath case and keeps the temperature at
37℃±0.5℃；Constant flow peristaltic pump flow velocity is adjusted to 0.5ml/min；Channel velocity every with the constant flow peristaltic pump that receiving chamber is connected is adjusted
To 1.0ml/min；Magnetic stirring apparatus is adjusted to " 5 " shelves.
(2), dispensing
Chimeric rat intestine in vitro between supply chamber, receiving chamber, after connecting line, adds medicine dissolution in medicine dissolution room
Liquid A, supply chamber adds medicine dissolution liquid A Yu pH and adjusts liquid, and receiving chamber adds reception liquid.Single pond bionic system brings into operation, and treats
Offer medicine after Wen Ding；Magnesium omeprazole enteric coatel tablets are offerd medicine a piece of (20mg/ sheet), parallel do 3 times.It is molten that medicine dissolution room is first passed through medicine
Solve liquid A, after 0.5 hour, switch to medicine dissolution liquid B.
(3), sample is collected
After dispensing, immediately begin to timing, start program control sample automatic collector, collect once through the every 10min of side sample.
(4), sample determination
HPLC method measures the content of omeprazole in sample.
Chromatographic condition: Waters600E (automatic sampler, deaerates online, quaternary gradient pump, 2487 detectors), chromatographic column
Agilent TC-C18 (5 μm, 4.6 × 150mm), flowing is water mutually: methanol (47: 53), and flow velocity is 1ml/min, detection wavelength:
302nm, column temperature 25 DEG C, sample size: 10 μ l
(5), data process
According to this for evaluating single bionic system dissolution side, pond (supply chamber) of delayed release formulation and through side (receiving chamber) number
According to, draw drug release rate-time graph, drug accumulation release-time graph, medicine transmitance-time graph, medicine are tired
Long-pending transmitance-time graph, and compare the dissolution result of use " pharmacopeia " said spin basket method and this list pond bionic system, with the softest
The releasing theory that part matching is different；According to Beagle dog experiment in vivo data, draw blood concentration-time curve, and with linear
Method of least square Regression, relies on method with chamber and calculates medicine pharmacokinetic studies in each time point Beagle dog body
The absorption percent drawn carries out linear regression investigation with it in this list pond bionic system corresponding accumulation transmitance, evaluates internal
Outer dependency.
(6), result and conclusion
Magnesium omeprazole, pKa=4.0, readily soluble in dichloromethane, the most molten in methanol or ethanol, slightly soluble in acetone,
In water insoluble；0.1mol/L sodium hydroxide solution dissolves.Dissolving situation in buffer salt solution is shown in Fig. 9.
Knowable to accompanying drawing 10, magnesium omeprazole enteric coatel tablets do not discharge at sour environment, and with the rising of pH value, medicine starts to release
Put, show that the single pond bionic system device for evaluating delayed release formulation of the present invention can reflect that preparation is discharged by pH value change
The impact of process.
With magnesium omeprazole enteric coatel tablets in the single pond bionic system device dissolution for evaluating delayed release formulation of the present invention
The result that the result of side gained draws with " pharmacopeia " said spin basket method compares.See accompanying drawing 11.
From the results, it was seen that magnesium omeprazole enteric coatel tablets are cut by simulated gastric fluid in " pharmacopeia " said spin basket method release medium
After being changed to simulated intestinal fluid, medicine discharges rapidly.And medicine is at the single pond bionic system for evaluating delayed release formulation of the present invention
In device, release embodies from stomach (pH 1-2) to the continuous dynamic process of the gradual change of intestinal (pH 6-8), is closer to human intestines and stomach
The physiological status of road pH change.Additionally, Rotating shaker can only response preparation cumulative release amount in single dissolution medium, and this use
The cumulative release amount of response preparation also can reflect that its transient change is tied in the single pond bionic system device evaluating delayed release formulation
Really, this is also that Rotating shaker is incomparable.
Magnesium omeprazole enteric coatel tablets are at the single pond bionic system device for evaluating delayed release formulation of the present invention and turn basket
Accumulation dissolution result in method, through Model fitting, the results are shown in Table 8.
Table 8 magnesium omeprazole enteric coatel tablets are through Model fitting result
From the point of view of degree of fitting, r value, closer to " 1 ", represents the goodness of fit maximum.Magnesium omeprazole enteric coatel tablets are in institute of the present invention
State the drug release process in the single pond bionic system device for evaluating delayed release formulation and Rotating shaker through Model fitting, all meet
First-order release model equation, i.e. this medicine are the one-level drug release process of non-constant velocity.Show that this is imitated for the single pond evaluating delayed release formulation
Raw system and device may be used for evaluating the Drug Release Kinetics feature of magnesium omeprazole enteric coatel tablets.
By the magnesium omeprazole enteric coatel tablets obtained for the single pond bionic system device evaluating delayed release formulation of the present invention
Transmitance-time graph, accumulation transmitance-time graph.See accompanying drawing 12,13.
With magnesium omeprazole enteric coatel tablets in the single pond bionic system device dissolution for evaluating delayed release formulation of the present invention
The Accumulation dissolution of side gained carries out non-linear dependencies investigation with the accumulation transmitance through side gained, and result is shown in Figure 14.
Assume that vitro Drug dissolution feature is equal to internal dissolution feature, and present first order kinetics under sink conditions
Release and first order kinetics pass through, it can be deduced that following relation:
Wherein α=kp/kd, i.e. one-level transmission rates constant is than one-level dissolution rate constant；faIt is that t is when infinity in body
Absorb percent.
Software MATLAB (version4.0) is used to carry out matched curve.Dissolution speed limit type medicine (α is more than 1) will produce " straight
Line style " relevant figure." inverted L shape " relevant figure will be produced through speed limit type medicine (α is less than 1).Speed limit type medicine is mixed through with dissolution
Thing (α approximates 1) will produce " hockey stick type " relevant figure.
It is readily seen from the relativity evaluation result of Figure 14: dependency r value is 0.9738, more than marginal value 0.8721, phase
Pass property is good.And α=2.158 ＞ 1, for " linear type " relevant figure, one-level transmission rates constant is more than one-level dissolution rate constant.
The evaluation information of the single pond bionic system device offer for evaluating delayed release formulation the most of the present invention is the most objective reliably, is better than
Rotating shaker.
The blood concentration-time curve of magnesium omeprazole enteric coatel tablets is obtained by pharmacokinetic studies in Beagle dog body.
See accompanying drawing 15.
To the magnesium omeprazole enteric coatel tablets result that pharmacokinetic studies draws in Beagle dog body with of the present invention
The result drawn through side in the single pond bionic system device evaluate delayed release formulation carries out relativity evaluation, selects medicine respectively
The body absorption percent that thing is corresponding respectively at 1,1.5,2,2.5,3,3.5,4,5 hours does dependency with accumulation transmitance and examines
Examining, check significance level a=0.001, r marginal value of tabling look-up is 0.9249.See accompanying drawing 16.
It is readily seen from the relativity evaluation result of Figure 16: dependency r value is 0.9313, more than marginal value 0.9249, phase
Pass property is good.Show through side character symbol zoarium internal procedure.Illustrate described for evaluating single pond bionic system of delayed release formulation
Device can be closer to the absorption process evaluating medicine of human body.
Data above represents, " pharmacopeia " described paddle method/Rotating shaker may only reflect the process in leaching of medicine, it is impossible to reflection medicine
Thing cross-film feature in vivo.And the single pond bionic system device for evaluating delayed release formulation of the present invention is possible not only to provide
The dissolution information of medicine, it is also possible to investigate the process of cross-film, a kind of technology platform that can be used as evaluating delayed release formulation describes late
Release formulation release and absorbing rule.
In sum, the single pond bionic system device for evaluating delayed release formulation of the present invention not only simulates human body life
Reason state stomach, intestinal pH change, and dynamic analog preparation travels to intestinal disintegrate, release from stomach, then intestinal across
The process that film absorbs.The enteric coatel tablets release rule in vitro by embodiment 10 success evaluation, to diclofenac sodium enteric-coated tablets and Austria
U.S.A draw azoles magnesium enteric coatel tablets the single pond bionic system device for evaluating delayed release formulation of the present invention and " pharmacopeia " described paddle method/
Drug release process in Rotating shaker, through Model fitting, all meets first-order release model equation, and i.e. two preparations are the one of non-constant speed
Level drug release process, shows that this is the same with paddle method/Rotating shaker for the single pond bionic system device evaluating delayed release formulation, may be used for
Evaluate the Drug Release Kinetics feature of two preparations, with two preparations at this for evaluating single pond bionic system device dissolution of delayed release formulation
The result that the result of side gained draws with paddle method/Rotating shaker compares, and shows that this system is substantially better than paddle method/Rotating shaker；Its
Secondary, the enteric coatel tablets absorbing rule by embodiment 11 success evaluation, magnesium omeprazole enteric coatel tablets are used for, at this, slowbreak system of evaluating
The result drawn with pharmacokinetic studies in Beagle dog body through side acquired results of single pond bionic system device of agent
Carry out relativity evaluation, it can be seen that this system passes through side character symbol zoarium internal procedure, illustrate described for evaluating slowbreak system
Single pond bionic system device of agent can be closer to the absorption process evaluating medicine of human body.
Additionally, the single pond bionic system device for evaluating delayed release formulation of the present invention can the release of on-line evaluation preparation
And absorption process, it is also easy to describe preparation release the most in the same time and Absorption Characteristics, obtains the release in preparation each moment continuously
Degree, Accumulation dissolution and transmembrane transport situation, can the release process of accurate measurements preparation, the cumulative release of matching preparation is write music
Line, observe medicine release behavior, with in " pharmacopeia " tradition dissolution determination method compared with, can continuous analog preparation at gastrointestinal tract
In disintegrate, release, absorption process, be better than the Dissolution Rate Testing method that existing " pharmacopeia " is recorded, this is used for evaluating delayed release formulation
Single pond bionic system device accurate simulation human body in gastrointestinal tract environment, truly reflect medicine dissolution in human body and suction
Receipts process, such that it is able to predict delayed release formulation release in human body and Absorption Characteristics.
Above-mentioned single pond bionic system device and the medicine dissolution being used for evaluating delayed release formulation to this with reference to detailed description of the invention
The detailed description that liquid is carried out with evaluation methodology, is illustrative rather than determinate, if can according to restriction scope list
Dry embodiment, therefore changing and modifications under without departing from present general inventive concept, within should belonging to protection scope of the present invention.
Claims (10)
1. the single pond bionic system device being used for evaluating delayed release formulation, it is characterised in that: mainly adjusted by medicine dissolution room, pH
Whole device, micropore filter and drug diffusion pond composition, be wherein provided with magnetic stir bar bottom medicine dissolution room, medicine dissolution indoor set
Having a medicine carrying device, leave distance between the magnetic stir bar bottom described medicine carrying device and medicine dissolution room, stainless steel mesh is put
Above this medicine carrying device；In described pH adjustor, implant is non-adsorbent filler；Drug diffusion pond by supply chamber, receiving chamber with
And it is entrenched in biomembrane tissue composition between the two；Described medicine dissolution room, pH adjustor, micropore filter and drug diffusion pond
It is sequentially connected with by the silica gel tube of internal diameter 1.0mm-2.0mm, is separately respectively equipped with at described medicine dissolution room, pH adjustor and receiving chamber
Sample holes, is additionally provided with air inlet and thief hole at described supply chamber and receiving chamber；
Wherein, during described evaluation delayed release formulation, described delayed release formulation is joined in the medicine carrying device of medicine dissolution room, first
Be passed through medicine dissolution liquid A, after switch to medicine dissolution liquid B；
Described medicine dissolution liquid A is mainly by NaCl, D-Glucose, CaCl2、MgSO4, MES and HCl that concentration is lmM composition, its
In in every 1000ml solution containing NaCl 7.8894g, D-Glucose 9.008g, CaCl2 0.2797g、MgSO4 0.0975g、
MES 1.9524g, concentration are the HCl 5.0mL of lmM, and remaining is water；
Described medicine dissolution liquid B is mainly by KC1, KH2PO4、NaCl、NaH2PO4, MES and Tris composition, wherein every 1000ml solution
In containing KC1 0.7977g, KH2PO4 0.1198g、NaCl7.8894g、NaH2PO40.0965g, MES 9.762g, Tris adjust
Joint pH value is to 6.8-7.8, and remaining is water.
Single pond bionic system device for evaluating delayed release formulation the most according to claim 1, it is characterised in that: described load
Medicine device is the medicine carrying basket being made by resistance to strong acid, resistance to highly basic, resistant to elevated temperatures stainless steel material or sheet metal folder.
Single pond bionic system device for evaluating delayed release formulation the most according to claim 1, it is characterised in that: described non-
Sorptive filler is sea sand or glass microsphere.
Single pond bionic system device for evaluating delayed release formulation the most according to claim 1, it is characterised in that: described micro-
Hole filter is changing device.
5. according to the single pond bionic system device for evaluating delayed release formulation described in claim 1 or 4, it is characterised in that: institute
Stating micropore filter aperture is 0.22 μm-0.8 μm.
6. according to the single pond bionic system device for evaluating delayed release formulation described in claim 1 or 4, it is characterised in that: institute
Stating micropore filter is synthetic fibers filter membrane.
7. according to the single pond bionic system device for evaluating delayed release formulation described in claim 1 or 4, it is characterised in that: institute
Stating micropore filter is quartz fibre filter membrane or glass fiber filter.
Single pond bionic system device for evaluating delayed release formulation the most according to claim 1, it is characterised in that: described life
Thing membrane tissue is Caco-2 and transgenic cell monofilm, MDCK and transgenic cell monofilm thereof or animal intestine in vitro.
Single pond bionic system device for evaluating delayed release formulation the most according to claim 1, it is characterised in that: described medicine
Thing dissolves room, pH adjustor and drug diffusion pond to be made up of clear perspex material.
10. the described single pond bionic system device applying one of claim 1-9 is evaluated delayed release formulation release and absorbs rule
The method of rule, it is characterised in that: concretely comprise the following steps: during mensuration, preparation is joined in the medicine carrying device of medicine dissolution room, be first passed through
Medicine dissolution liquid A, after switch to medicine dissolution liquid B；By constant flow peristaltic pump, the drug transfer dissolved is adjusted to pH adjustor with pH
Whole liquid mixes, and is transferred to the supply chamber in drug diffusion pond the most further, and constantly enters medicine reception through biomembrane tissue
Room, respectively from supply chamber and receiving chamber sampling and measuring.
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| CN104458504A (en) * | 2013-09-16 | 2015-03-25 | 中国科学院大连化学物理研究所 | Diffusion cell membrane module and diffusion cell |
| CN103881977B (en) * | 2014-02-26 | 2016-12-07 | 浙江大学 | Coexpression absorbs transporter and the structure of drug metabolism catalator and application |
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| CN111356919A (en) * | 2020-02-21 | 2020-06-30 | 南京海维医药科技有限公司 | Auxiliary device for dissolution test |
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- 2011-04-20 CN CN2011201163385U patent/CN202033355U/en not_active Expired - Fee Related
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| US5807115A (en) * | 1996-01-31 | 1998-09-15 | Hu; Oliver Yoa-Pu | Dissolution apparatus simulating physiological gastrointestinal conditions |
| CN101639471A (en) * | 2009-08-21 | 2010-02-03 | 天津中医药大学 | Device for evaluating dissolving/absorbing process of medical solid preparation |
| CN201488990U (en) * | 2009-08-21 | 2010-05-26 | 天津中医药大学 | Bionic system device for valuating medicine solid preparation |
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| CN102253173A (en) | 2011-11-23 |
| CN202033355U (en) | 2011-11-09 |
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