CN109030398A - A kind of buccal cigarette nicotine release behavior detection method and its special test equipment - Google Patents
A kind of buccal cigarette nicotine release behavior detection method and its special test equipment Download PDFInfo
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- CN109030398A CN109030398A CN201810987568.5A CN201810987568A CN109030398A CN 109030398 A CN109030398 A CN 109030398A CN 201810987568 A CN201810987568 A CN 201810987568A CN 109030398 A CN109030398 A CN 109030398A
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- nicotine
- buccal cigarette
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- releasing unit
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- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims abstract description 111
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims abstract description 111
- 229960002715 nicotine Drugs 0.000 title claims abstract description 111
- 235000019504 cigarettes Nutrition 0.000 title claims abstract description 81
- 238000001514 detection method Methods 0.000 title claims abstract description 61
- 238000012360 testing method Methods 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 27
- 229940079593 drug Drugs 0.000 claims abstract description 24
- 238000004090 dissolution Methods 0.000 claims abstract description 20
- 238000005516 engineering process Methods 0.000 claims abstract description 16
- 210000000214 mouth Anatomy 0.000 claims abstract description 14
- 238000000338 in vitro Methods 0.000 claims abstract description 8
- 238000012545 processing Methods 0.000 claims abstract description 8
- 238000012986 modification Methods 0.000 claims abstract description 6
- 230000004048 modification Effects 0.000 claims abstract description 6
- 239000000835 fiber Substances 0.000 claims abstract description 5
- 238000010183 spectrum analysis Methods 0.000 claims abstract description 5
- 239000000523 sample Substances 0.000 claims description 52
- 238000002835 absorbance Methods 0.000 claims description 31
- 239000007788 liquid Substances 0.000 claims description 25
- 239000012535 impurity Substances 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 239000000120 Artificial Saliva Substances 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000011156 evaluation Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 3
- 239000011521 glass Substances 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- 238000013178 mathematical model Methods 0.000 claims description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 1
- 239000010931 gold Substances 0.000 claims 1
- 229910052737 gold Inorganic materials 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 235000019505 tobacco product Nutrition 0.000 abstract description 7
- 238000004458 analytical method Methods 0.000 abstract description 6
- 239000000779 smoke Substances 0.000 abstract description 5
- 238000003908 quality control method Methods 0.000 abstract description 4
- 238000013461 design Methods 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 238000010223 real-time analysis Methods 0.000 abstract description 2
- 238000010948 quality risk assessment Methods 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 16
- 241000208125 Nicotiana Species 0.000 description 10
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 5
- 238000002386 leaching Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 4
- 210000003296 saliva Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000012086 standard solution Substances 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000006101 laboratory sample Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000013456 study Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
Abstract
The invention belongs to smoke-free tobacco product the field of test technology, it is specifically a kind of buccal cigarette nicotine release behavior detection method and special test equipment, it is characterized in that: according to the consumptive characteristics of packed buccal cigarette, the structure of modification for being suitable for buccal cigarette test is carried out to existing drug dissolution instrument, it is proposed that analog buccal cigarette nicotine carries out in-vitro simulated test to packed buccal cigarette nicotine release behavior in the external detection method of oral cavity release behavior, and in conjunction with fiber optic conduction technology, ultraviolet spectral analysis technology and microcomputer data processing.The great advantage of this method is: realizing external continuous analysis, in real time analysis and the on-line analysis of buccal cigarette nicotine release behavior, and provides important technical support and scientific basis with favorable reproducibility, high degree of automation, the product design to suck smoke product, quality control, risk assessment and policy-making.
Description
Technical field
The present invention relates to smoke-free tobacco product ingredient release behavior vitro detection technical fields, and in particular to a kind of mouth containing
Cigarette nicotine release behavior detection method and its special test equipment bag, can be used for nicotine ingredient in buccal smokeless tobacco product
The external continuous online instant qualitative and quantitative detection of release, i.e., the release of nicotine ingredient in bagged buccal smokeless tobacco product
Degree (%) and rate of release (μ gs-1) instant on-line checking.
Background technique
Packed buccal cigarette is that the tobacco wet-milling after processing is encapsulated in penetrability pouch, and when consumption places it on oral cavity
Between lip and gum, without chewing, tobacco component discharges into oral cavity after saliva is dissolved and passes through oral mucosal absorption.In recent years
Come, continuous stringent with world's Policy on smoke control, the place that can smoke increasingly reduces, and the packed buccal cigarette of the smokeless of oral consumption is made
The important market share is occupied in North America, Northern Europe for the important supplement form of tobacco consumption, the country also has within the border same outside the Pass
Type products listing, buccal cigarette chemical composition analysis, formula dissect and the correlative studys such as technological forming technology also become in recent years
Tobacco research hotspot.
Nicotine is tobacco main alkaloid, nicotine rate of release (μ gs-1) and releasing degree (or cumulative release amount, %) be
One of the important indicator of buccal cigarette product quality.On the one hand nicotine release behavior extracorporeal simulating experiment can filter out reasonable original
On the other hand material formula and production technology can measure the risk assessment of buccal cigarette, enhanced products Quality Control means.
In order to reach the effective control discharged to nicotine in buccal cigarette, various countries have carried out the reality of some nicotine release aspects
Test room research work.1998, Nasr etc. had studied the release conditions of buccal cigarette nicotine with a kind of homemade dialysis apparatus.The party
Buccal cigarette is placed in a bag filter by method, is then placed in artificial saliva, and different time points nicotine is studied by interval sampling
Release characteristic.This method is relatively simple, but is restricted using the nicotine rate of release that the device measures by bag filter, it is difficult to anti-
Reflect the release conditions of nicotine in sample.1999, buccal cigarette was placed in supported liquid membrane device by Luque-P é rez etc., in conjunction with
The burst size of UV spectrophotometer measuring nicotine.Though this method can achieve the purpose that detect nicotine burst size, supported liquid membrane
Unstable, measurement result fluctuation is larger.2011, outstanding person etc., which has developed, a set of can simulate what buccal cigarette nicotine discharged in oral cavity
Release in vitro device, and the release of nicotine in buccal cigarette and free nicotine is analyzed using the device, which is state
Interior first set buccal cigarette nicotine extracorporeal releasing experiment device, can simulate release behavior, distinguish the nicotine release between different samples
Difference, but for laboratory zero install it is standby, it is cumbersome, be not easy to promote and apply.
Drug dissolution instrument is the common detection device of medicine field, is to carry out dissolution data detection to preparations such as tablets
Special instrument, but do not find other fields, particularly Field of Tobacco carry out using.
Summary of the invention
The purpose of the present invention is for nicotine release in current bagged buccal smokeless tobacco product (abbreviation buccal cigarette)
The deficiency of behavioral value method, provide it is a kind of can in continuous on-line determination buccal cigarette release in vitro liquid nicotine content detection side
Method and special test equipment suitable for this method, by means of the present invention and special instrument can be made instantly available in release liquid
Nicotine content, and draw concentration changes with time curve, i.e. buccal cigarette nicotine release behavior curve.The present invention is directed to be packed mouth
Nicotine release detection and regulation containing cigarette provide technical support and data reference, while being engaged in mouth containing smoke product for tobacco business and opening
The related personnel of the work such as hair, Quality Control provides the accurate detection method and skill easy to promote and utilize of buccal cigarette nicotine release behavior
Art platform.
The invention mechanism of this method is: according to the consumptive characteristics of packed buccal cigarette, to existing drug dissolution instrument into
Row is suitable for the structure of modification of buccal cigarette test, propose it is a kind of can simulate packed buccal cigarette nicotine discharged in oral cavity it is external
Detection method, and combine fiber optic conduction technology, ultraviolet spectral analysis technology and microcomputer data processing to packed mouth containing
Cigarette nicotine release behavior is described.Theoretical principle is as described below based on data processing software involved in it:
Since buccal cigarette release liquid is multicomponent mixed system, principle can be summed it up according to absorbance:
Formula 1
In formula 1, ε is absorptivity, and C is concentration,lFor light path.
The spectrogram of nicotine standard product, the spectrogram of available impurity are subtracted using the spectrogram of soak.That is:
ΔA=ALeaching-ANicFormula 2
In formula 2, Δ A is the absorbance of impurity in soak, ALeachingFor soak absorbance, ANicFor the extinction of nicotine standard product
Degree.
Assuming that k=(Δ A1-ΔA3)/( ΔA2-ΔA3) formula 3
In formula 3, Δ A1For wavelength X1The impurity absorbance at place, wavelength selection principle are nicotine maximum absorption wavelength, i.e. 260nm；
ΔA2For reference wavelength λ2The impurity absorbance at place, wavelength selection principle are nicotine without absorption, and impurity has stronger absorption, i.e.,
290nm；ΔA3For reference wavelength λ3The impurity absorbance at place, wavelength selection principle are nicotine without absorption, and Impurity Absorption is weaker or nothing
It absorbs, i.e. 550nm.
Formula 1 is substituted into formula 3, it may be assumed that
k=(ΔA1-ΔA3)/( ΔA2-ΔA3)=[(ε1-ε3)/(ε2-ε3)] * C*l, due to C,lFor fixed value, therefore k is normal
Number, and Δ A can be passed through1、ΔA2、ΔA3Value calculate and obtain.
By formula 2 it is found that A1 Nic=A1 Leaching-ΔA1 Formula 4
Wherein, A1 NicIt is nicotine standard product in wavelength X1The absorbance at place, A1 LeachingIt is sample soak in wavelength X1The absorbance at place,
ΔA1It is impurity in sample soak in wavelength X1The absorbance at place.
By formula 3 it is found that Δ A1=k(Δ A2-ΔA3)+Δ A3=kΔA2-(k-1)ΔA3 Formula 5
Formula 5 is substituted into formula 4, it may be assumed that
A1 Nic=A1 Leaching- kΔA2-(k-1)ΔA3 Formula 6
In formula 6, due to Δ A2For reference wavelength λ2The impurity absorbance at place, wavelength selection principle are nicotine without absorption, and impurity has
It is relatively strong to absorb；ΔA3For reference wavelength λ3The impurity absorbance at place, wavelength selection principle are nicotine without absorption, and Impurity Absorption is weaker
Or without absorption.It is considered that: Δ A2= A2 Leaching, Δ A3= A3 Leaching.Therefore, formula 6 can be stated are as follows:
A1 Nic=A1 Leaching- k A2 Leaching-(k-1) A3 LeachingFormula 7
In conclusion nicotinic density can be according to λ immediately1、λ2And λ3The absorbance value at place is calculated, powerful based on computer
Computing function, nicotinic density in system can be made instantly available on data processing software, and draw nicotinic density and become at any time
Change curve, i.e., packed buccal cigarette nicotine release behavior curve.
The purpose of the present invention is achieved through the following technical solutions:
A kind of buccal cigarette nicotine release behavior detection method, be according to the consumptive characteristics of packed buccal cigarette, it is molten to existing drug
Out-degree instrument carries out the structure of modification for being suitable for buccal cigarette test, proposes analog buccal cigarette nicotine in the external of oral cavity release behavior
Detection method, and combine fiber optic conduction technology, ultraviolet spectral analysis technology and microcomputer data processing to packed mouth containing
Cigarette nicotine release behavior carries out in-vitro simulated test, and the specific method is as follows:
1) existing drug dissolution instrument is transformed, obtains the special instrument for being suitable for the detection of buccal cigarette nicotine release behavior；
2) the packed buccal cigarette sample of 1 parcel is taken to be placed in (position in the narrow releasing unit of draining formula of improved special instrument
In on liquid level), artificial saliva, which flows through, to be taken component to be measured after sample out of and instills detection cup, fibre-optical probe be placed in detection cup liquid level it
Under, the absorbance value of detection release liquid system.It is fixed that relationship according to nicotinic density and nicotine absorbance meets Lambert-Beer
Rule deducts impurity effect using drug-eluting data processing software (drug dissolution instrument included), obtains nicotine in system i.e.
When concentration, and record system nicotinic density per second at any time, and then draw buccal cigarette nicotine release behavior curve；
3) release rate is added up to nicotine using Weibull model and carries out Mathematical Evaluation；Weibull model is that pharmaceutical field is common
The mathematical model of drug release situation is evaluated, for describing drug in the preparation of t moment, form is as follows: Y=1-exp
(- α * t) μ, Y is preparation in formula, and α is that scale parameter determines that the time scale of release process, μ are that form parameter is determined
The shape feature of curve is determined, the curve of μ=1 is exponential type, and μ>1 is S-shaped, and μ<1 is the index shape song for starting steeper slope
Line；μ=1 in this method, the shape of matched curve depend primarily on α, i.e. the accumulative release rate of nicotine at any time is determined by α, α's
Size can reflect the speed of nicotine release, therefore defining α is nicotine rate of release coefficient (min-1), it can be by comparing the number of α
Value judges the speed of different sample nicotine release；The final overall process for realizing buccal cigarette nicotine release behavior vitro detection.
A kind of special test equipment suitable for above-mentioned detection method, the drug dissolution instrument including having fibre-optical probe, medicine
The shaft lower end of object dissolution rate instrument is connected with the narrow releasing unit of draining formula for placing sample, and shaft is by mixing control device control
System, in which: the shaft of drug dissolution instrument transform hollow rotating shaft as, hollow rotating shaft lower end by a clamping hoop type connector with it is above-mentioned
Releasing unit is combined together, and the releasing unit is rotated with hollow rotating shaft.One is coated in the hollow rotating shaft by flow control
The artificial saliva drip tube of device control processed, drip tube lower end is stretched out by hollow rotating shaft lower end to be extended in the releasing unit, is released
It puts and is placed with detection cup below unit, detection cup is arranged in constant water bath box.(being detailed in Fig. 1)
The narrow releasing unit capacity of draining formula is 5-15cm3, preferably 10cm3,, bottom is evenly equipped with drain hole；Releasing unit
Shape can be cylindrical body, cuboid or square, and material can be the materials such as metal, macromolecule, glass.
The mixing component extended downwardly is provided in releasing unit bottom, for being stirred, mixing to liquid in detection cup
It closes uniform.The mixing component can be a stirring rod, threadedly directly be screwed releasing unit bottom (referring to Fig. 1)；?
It can be a snap ring multi-claw type stirring parts, be directly installed on releasing unit excircle wall surface by clamping mode.(referring to fig. 2)
Detection cup capacity is 100-300cm3, preferably 200cm3,, shape can be cylindrical body, cuboid or square, material
It can be the materials such as metal, macromolecule, glass.
Slit on the fibre-optical probe is 0.1-5mm, preferably 1mm, and fibre-optical probe is located at the side of detection cup, and position is solid
It is fixed.
Performance Liquid Chromatography Analysis for Nicotine in Tobacco ingredient is after saliva is dissolved when the application method of this special test equipment is simulation buccal cigarette use
The consumptive characteristics for discharging entrance cavity, take the packed buccal cigarette sample of 1 parcel to be placed in the narrow releasing unit of draining formula, and artificial saliva is permanent
Speed takes component instillation detection cup to be measured out of after flowing through sample, and fibre-optical probe is placed under detection cup liquid level, detects release liquid absorbance,
Relationship according to nicotinic density and nicotine absorbance meets Lambert-Beer law, i.e. nicotinic density is in nicotine absorbance
Linear relationship, after carrying out data processing using data processing software (drug dissolution instrument is included), the nicotine obtained in system is dense
Degree, and draw nicotine and change over time curve, i.e. buccal cigarette nicotine release behavior curve.Detailed Experimental process are as follows:
A. it is switched on, preheats, water-bath takes appropriate amount of purified water to be added in detection cup to 37 DEG C, is placed in detection after taking 1 bag of samples weighing
Under cup liquid level, stirring is impregnated one hour under the conditions of water bath with thermostatic control, takes out sample, obtains soak, detects λ1、λ2、λ3Locate absorbance
Value.
B. it takes above-mentioned soak into chromatogram bottle, through high performance liquid chromatography detection, obtains nicotinic density.
C. same concentration nicotine standard specimen solution is prepared, λ is measured1、λ2、λ3Locate absorbance value, calculates k value and typing software.
D. it is switched on, preheats, water-bath separately takes appropriate amount of purified water into detection cup to 37 DEG C, and fibre-optical probe immerses underwater.Separately
It is flat on narrow releasing unit bottom after taking 1 bag of samples weighing, releasing unit is located on the water surface.Peristaltic pump is opened, with suitable
Between flow velocity drips artificial saliva at the uniform velocity in the sample.
E. stirring is opened simultaneously, and starts timing, instrument starts to detect and record.
F. after a period of time, stop testing and save file.
G. according to experimental test data, the value that nicotine adds up release rate % and rate of release factor alpha is calculated.
The present invention has the advantages that
1. experimental method of the present invention have stronger novelty, merged optical fiber technology, spectral technique, analytical technology and
Computer technology is integrated, sample time, detection time interval with the second grade accurately calculate, innovatively realize buccal cigarette
External continuous analysis, in real time analysis and the on-line analysis of nicotine release behavior.
2. measuring method of the present invention has the characteristics that favorable reproducibility, high degree of automation, convenient for promoting, can be effective
In-vitro simulated buccal cigarette nicotine release behavior, practical, to suck, the product design of smoke product, quality control, risk commented
Estimate and policy-making provides important technical support and scientific basis.
Detailed description of the invention
Fig. 1 is the special test equipment structural schematic diagram of buccal cigarette nicotine release behavior of the present invention
Fig. 2 is the structural schematic diagram that the narrow releasing unit of draining formula is connect with other components in Fig. 1
In figure, 1. drug dissolution instrument, 2. fibre-optical probes, 3. hollow rotating shafts, 4. narrow releasing units, 5. clamping hoop type connectors,
6. drip tube, 7. mixing control devices, 8. artificial salivas, 9. flow controllers, 10. artificial saliva housing instills mouths, 11. mixing parts
Part, 11-1. snap ring multi-claw type stirring parts, 12. samples, 13. constant water bath box, 14. detection cups.
Fig. 3 is domestic single-tobacco-typed cigarette G1# sample soak full wavelength scanner figure.
Fig. 4 is 49.9 μ g/ml nicotine standard specimen full wavelength scanner figures.
The domestic single-tobacco-typed cigarette G1# sample nicotine In-vitro release curves of Fig. 5.
Specific embodiment
The present invention is described further detection method below in conjunction with attached drawing:
Buccal cigarette nicotine release behavior detection method of the invention, is according to the consumptive characteristics of packed buccal cigarette, to existing medicine
Object dissolution rate instrument carries out the structure of modification for being suitable for buccal cigarette test, proposes analog buccal cigarette nicotine in oral cavity release behavior
External detection method, and combine fiber optic conduction technology, ultraviolet spectral analysis technology and microcomputer data processing to packed
Buccal cigarette nicotine release behavior carries out in-vitro simulated test, and the specific method is as follows:
1) existing drug dissolution instrument is transformed, obtains the special instrument for being suitable for the detection of buccal cigarette nicotine release behavior
(referring to Fig. 1)；
2) the packed buccal cigarette sample 12 of 1 parcel is taken to be placed in the narrow releasing unit 4 of draining formula of improved special instrument
(being located on liquid level), artificial saliva take component instillation detection cup to be measured out of after flowing through sample, and fibre-optical probe 2 is placed in 14 liquid of detection cup
Under face, the absorbance value of detection release liquid system.Relationship according to nicotinic density and nicotine absorbance meets Lambert-
Beer law deducts impurity effect using drug-eluting data processing software (drug dissolution instrument is included), obtains in system
The instant concentration of nicotine, and system nicotinic density per second is recorded at any time, and then draws buccal cigarette nicotine release behavior curve；
3) release rate is added up to nicotine using Weibull model and carries out Mathematical Evaluation；Weibull model is that pharmaceutical field is common
The mathematical model of drug release situation is evaluated, for describing drug in the preparation of t moment, form is as follows: Y=1-exp
(- α * t) μ, Y is preparation in formula, and α is that scale parameter determines that the time scale of release process, μ are that form parameter is determined
The shape feature of curve is determined, the curve of μ=1 is exponential type, and μ>1 is S-shaped, and μ<1 is the index shape song for starting steeper slope
Line；μ=1 in this method, the shape of matched curve depend primarily on α, i.e. the accumulative release rate of nicotine at any time is determined by α, α's
Size can reflect the speed of nicotine release, therefore defining α is nicotine rate of release coefficient (min-1), it can be by comparing the number of α
Value judges the speed of different sample nicotine release；The final overall process for realizing buccal cigarette nicotine release behavior vitro detection.
Special test equipment of the invention is illustrated below in conjunction with attached drawing:
It is as shown in Figure 1, 2: a kind of special test equipment suitable for above-mentioned detection method, the drug-eluting including having fibre-optical probe
Instrument 1 is spent, the shaft lower end of drug dissolution instrument is connected with the narrow releasing unit 4 of draining formula for placing sample, and shaft is by stirring
Mix the control of controller 7, in which: the shaft of drug dissolution instrument transform hollow rotating shaft 3 as, and 3 lower end of hollow rotating shaft passes through a clip
Formula connector 5 is combined together with above-mentioned releasing unit 4, and the releasing unit is rotated with hollow rotating shaft.In the hollow rotating shaft 3
It is coated with an artificial saliva drip tube 6 controlled by flow controller 9, drip tube lower end is stretched out by hollow rotating shaft lower end to be extended to
In the releasing unit 4, detection cup 14 is placed with below releasing unit, detection cup is arranged in constant water bath box 13.
The mixing component 11 extended downwardly is provided in releasing unit bottom, for being stirred to liquid in detection cup,
It is uniformly mixed.The mixing component 11 can be a stirring rod, threadedly directly be screwed releasing unit bottom (referring to figure
1)；It can also be a snap ring multi-claw type stirring parts 11-1, be directly installed on 4 excircle wall surface of releasing unit by clamping mode.
(referring to fig. 2)
Specific test and implementation result
Following embodiment is merely to illustrate the range of the present invention and is not intended to limit the present invention.In addition, it should also be understood that, having read this
After inventing the content, those skilled in the art can make various changes and modification to the present invention, these equivalent forms are same
Fall within the application range as defined in the appended claims.
One, domestic single-tobacco-typed cigarette experimental procedure
1. sample preparation: originating from the Domestic Flue-cured Tobacco, burley tobaccos, sunning 9, cigarette sample in the area such as Guangxi, Hubei, Sichuan, Yunnan.
After the process such as crushing, screening, curing, packaging, self-control obtains buccal cigarette laboratory sample, and all samples seal before testing
Stored frozen (18 DEG C).
2. take the domestic single-tobacco-typed cigarette sample that number is G1,37 DEG C of constant temperature impregnate 1 hour after take out sample and obtain soak.Entirely
Length scanning detects its absorbance value (result such as Fig. 3), and reading wavelength is respectively the absorbance value at 260nm, 290nm, 550m.
3. detecting G1# sample soak nicotinic density using high performance liquid chromatography, obtaining nicotinic density is 49.9 μ g/
ml。
4. manually nicotine standard specimen solution of the saliva compound concentration close to 49.9 μ g/ml.Full wavelength scanner detects its extinction
Angle value (result such as Fig. 4), reading wavelength is respectively the absorbance value at 260nm, 290nm, 550m.
5. according to soak and standard specimen solution in the absorbance value that wavelength is the place 260nm, 290nm, 550nm, calculating k=
1.24。
6. repeating step the 2-5 step totally 3 times, taking 3 parallel laboratory test average values 1.24 is k value.(step can be omitted)
7. separately taking 1 bag of sample, it is flat on releasing unit bottom, releasing unit is located on liquid level, and fibre-optical probe is located under liquid level.It releases
The mixing part for putting unit lower part is located under liquid level.
8. after covering detection cup/lid, opening peristaltic pump and artificial saliva being driven at the uniform velocity to drip with fixed flow rate 0.2ml/min
Among sample, detection cup is instilled after taking buccal cigarette release ingredient out of.Stirring is opened simultaneously, whole experiment process keeps detection cup lid
Sub- closed state is to reduce moisture evaporation in experimentation.
9. after experiment starts, instrument starts detection and timing.
10. after 45min, can see release liquid system absorbance value by experiment view window and tend towards stability, stop at this time
It only tests and saves file.
11. using excel or origin software data processing, and drawing nicotine release behavior curve according to experimental data
As shown in Figure 5.
12. the nicotine rate of release α that domestic single-tobacco-typed cigarette G1# sample is calculated is 0.04 according to experimental data.It (is detailed in
Table 2)
13. repeating experimental procedure 2-10, the Nicotine Accumulation releasing curve diagram of remaining available 8 sample.
14. repeating experimental procedure 12, the nicotine rate of release α of remaining available 8 sample.(see Table 2 for details)
Two, external commercially available tobacco product experimental procedure
The commercially available buccal cigarette sample of foreign countries that number is 1-10# is taken, " one, domestic single-tobacco-typed cigarette experimental procedure " 2-12 step is repeated, it can
To obtain the Nicotine Accumulation releasing curve diagram and nicotine rate of release α of 10 samples.(see Table 2 for details)
Three, implementation result
1. the absorbance stability of experimental method of the present invention, linearity and range
Matched series of concentrations nicotine standard solution is taken, is detected with special test equipment of the invention, calibration curve, linear side are obtained
Journey and related coefficient.The experimental results showed that in the range of 10-80ug/ml, absorbance of the nicotine standard solution at 260nm
Stablize the time greater than 1 hour.In the concentration range of 10-80ug/ml, absorbance of the nicotine standard solution at 260nm with it is dense
The linear relationship of degree is good, Regressive calibration curve equation are as follows: y=270.88x+0.3522,r =0.9993。
2. the repeatability of experimental method of the present invention
By sample to be tested in thaw at RT 2h, 100 pouches is taken to calculate sample average quality, carries out sample point by average quality ± 1%
Choosing, takes qualified samples, carries out the experiment of nicotine release by the experiment flow of 1.2.3, Parallel testing 6 times, calculates each period cigarette
Alkali adds up the relative standard deviation (RSD) of release rate, the results are shown in Table 1.
The repeatability (n=6, RSD %) of 1 method of table
The relative standard deviation of each period sample burst size shows that method has preferable repeat between the % of 3.4 %~7.4
Property.
3. the interpretation of result of experimental method of the present invention
Weibull models fitting is carried out to the nicotine release data of domestic single-tobacco-typed cigarette and external commercial product buccal cigarette, is as a result seen
Table 2, as a result, it has been found that, the goodness of fit of every kind of sample is all larger than 0.96, show that Weibull model is suitble to this nicotine method for releasing,
Using the nicotine rate of release of Weibull model evaluation buccal cigarette, nicotine burst size in each time is predicted.
The nicotine rate of release coefficient of the different buccal cigarettes of table 2
| Sample serial number | Moisture content (%) | pH | Nicotine (mg/g) is in terms of weight in wet base | Releasing degree (%) | Discharge digit rate coefficient lambda (min-1) |
| Domestic single-tobacco-typed cigarette 1 | 22.2 | 4.78 | 27.5 | 89 | 0.04 |
| 2 | 24.7 | 5.07 | 18.7 | 96 | 0.07 |
| 3 | 26.9 | 4.91 | 31.9 | 79 | 0.03 |
| 4 | 26.5 | 4.64 | 23.3 | 96 | 0.07 |
| 5 | 25.1 | 4.76 | 33.1 | 85 | 0.03 |
| 6 | 25.4 | 7.35 | 16.3 | 97 | 0.06 |
| 7 | 28.4 | 7.00 | 27.7 | 80 | 0.02 |
| 8 | 24.9 | 7.06 | 19.0 | 70 | 0.02 |
| 9 | 23.6 | 6.98 | 26.2 | 94 | 0.05 |
| External tobacco product 1 | 41.0 | 6.68 | 8.0 | 94 | 0.06 |
| 2 | 45.4 | 6.33 | 8.0 | 85 | 0.04 |
| 3 | 38.1 | 7.35 | 11.1 | 51 | 0.02 |
| 4 | 31.0 | 6.02 | 10.4 | 97 | 0.06 |
| 5 | 37.1 | 6.67 | 15.0 | 83 | 0.04 |
| 6 | 18.2 | 6.22 | 14.3 | 96 | 0.07 |
| 7 | 26.8 | 6.33 | 16.5 | 62 | 0.02 |
| 8 | 24.8 | 7.48 | 7.7 | 99 | 0.11 |
| 9 | 44.6 | 6.84 | 14.2 | 96 | 0.08 |
| 10 | 47.7 | 6.57 | 20.0 | 88 | 0.04 |
Claims (7)
1. a kind of buccal cigarette nicotine release behavior detection method, it is characterised in that: according to the consumptive characteristics of packed buccal cigarette, to existing
Some drug dissolution instrument carry out the structure of modification for being suitable for buccal cigarette test, propose that analog buccal cigarette nicotine discharges in oral cavity
The detection method of behavior, and combine fiber optic conduction technology, ultraviolet spectral analysis technology and microcomputer data processing to bag
It fills buccal cigarette nicotine release behavior and carries out in-vitro simulated test, the specific method is as follows:
Existing drug dissolution instrument is transformed, the special instrument for being suitable for the detection of buccal cigarette nicotine release behavior is obtained；
The packed buccal cigarette sample of 1 parcel is taken to be placed in the narrow releasing unit of draining formula of improved special instrument, artificial saliva
Component instillation detection cup to be measured is taken out of after flowing through sample, and fibre-optical probe is placed under detection cup liquid level, detection release liquid system
Absorbance value, the relationship according to nicotinic density and nicotine absorbance meet Lambert-Beer law, utilize drug-eluting data
Processing software deducts impurity effect, obtains the instant concentration of nicotine in system, and record system nicotinic density per second at any time, into
And draw buccal cigarette nicotine release behavior curve；
Release rate is added up to nicotine using Weibull model and carries out Mathematical Evaluation；Weibull model is that pharmaceutical field is commonly commented
The mathematical model of valence drug release situation, for describing drug in the preparation of t moment, form is as follows: Y=1-exp (-
α * t) μ, Y is preparation in formula, and α is that scale parameter determines that the time scale of release process, μ are that form parameter determines
The shape feature of curve, the curve of μ=1 are exponential type, and μ>1 is S-shaped, and μ<1 be the exponential like curve of beginning steeper slope；
μ=1 in this method, the shape of matched curve depend primarily on α, i.e. the accumulative release rate of nicotine at any time is determined by α, the size of α
It can reflect the speed of nicotine release, therefore defining α is nicotine rate of release coefficient (min-1), it can come by comparing the numerical value of α
Judge the speed of different sample nicotine releases；The final overall process for realizing buccal cigarette nicotine release behavior vitro detection.
2. a kind of special test equipment suitable for detection method described in claim 1, the drug-eluting including having fibre-optical probe
Instrument is spent, the shaft lower end of drug dissolution instrument is connected with the narrow releasing unit of draining formula for placing sample, and shaft is by stirring
Controller control, it is characterised in that: the shaft of drug dissolution instrument is hollow rotating shaft, and hollow rotating shaft lower end is connected by a clamping hoop type
Fitting is combined together with the releasing unit, and the releasing unit is rotated with hollow rotating shaft；It is coated in the hollow rotating shaft
The one artificial saliva drip tube controlled by flow controller, drip tube lower end is stretched out by hollow rotating shaft lower end extends to releasing unit
In, detection cup is placed with below releasing unit, detection cup is arranged in constant water bath box.
3. special test equipment according to claim 2, it is characterised in that: the narrow releasing unit of draining formula is located at body
It is ullage, contactless with liquid level, fibre-optical probe is located at below liquid level, is soaked in system.
4. special test equipment according to claim 2 or 3, it is characterised in that: the narrow releasing unit of draining formula holds
Product is 5-10 cubic centimetres, preferably 10 cubic centimetres；Shape can be drum-shaped, cuboid or the square bodily form, and material can be gold
Belong to material, macromolecule material or glass material.
5. special test equipment according to claim 2 or 3, it is characterised in that: in the narrow releasing unit bottom of draining formula
It is provided with mixing component, for being stirred, being uniformly mixed to liquid in detection cup.
6. special test equipment according to claim 5, it is characterised in that: the mixing component is a stirring rod, is passed through
Engagement thread is directly screwedly mounted on releasing unit bottom.
7. special test equipment according to claim 5, it is characterised in that: the mixing component is that a snap ring multi-claw type stirs
Part is mixed, is directly installed in releasing unit bottom cylindrical peripheral wall surfaces by clamping mode.
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