CN104155263B - A kind of analysis method of medicinal tablet uniform quality sex-related factors - Google Patents
A kind of analysis method of medicinal tablet uniform quality sex-related factors Download PDFInfo
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Abstract
The present invention relates to a kind of analysis method of medicinal tablet uniform quality sex-related factors, it is specifically related to tablet active pharmaceutical ingredient content, tablet weight and sheet tensile strength are carried out variance analysis, to determine the correlative factor of medicinal tablet quality uniformity, provide foundation for formulating the control program of production process.Belong to pharmaceutical preparation quality analysis field.Comprise the following steps: 1. collect medicinal tablet sample；The mensuration of the most each correlative factor value；Calculate the most respectively each correlative factor value batch in, batch between and inter-plant variance yields；4. compare analysis to the corresponding generalized variance value using Fourier transform near infrared spectrum method to obtain；5. medicinal tablet criticizes the Related factors of interior quality uniformity；6. medicinal tablet criticizes the Related factors of a quality uniformity；7. the Related factors of medicinal tablet inter-plant quality uniformity.The present invention can be that the quality uniformity improving medicinal tablet provides technical support.
Description
Technical field
The present invention relates to a kind of analysis method of medicinal tablet uniform quality sex-related factors, be specifically related to use variance to divide
The active pharmaceutical ingredient content of tablet medicine is made a variation by analysis method, tablet weight makes a variation and the variation of sheet tensile strength is analyzed, to determine
The main associated factors of medicinal tablet quality uniformity, the formulation for medicinal tablet production process quality uniformity control program carries
For foundation and reference.Belong to pharmaceutical preparation quality analysis field.
Background technology
Guarantee to produce sustainedly and stably and meet intended purpose and medicine that registration requires is that China implements version " medicine in 2010
Product quality of production management regulation " one of the main purpose of (Good Manufacture Practice of Drugs, GMP).But
Implementation status due to supplementary material, production technology, production status and GMP etc. are incomplete same, make the quality of medicinal tablet exist
Inhomogeneities.Formulation for medicinal tablet production process quality uniformity control program provides foundation, and improves medicinal tablet matter
The uniformity of amount, it is necessary to the correlative factor of medicinal tablet quality uniformity is analyzed.
The correlative factor affecting medicinal tablet quality uniformity is a lot.Wherein, active pharmaceutical ingredient in medicinal tablet
The content of (active pharmaceutical ingredient, API) is the most relevant to drug effect, so the variation of API content is
Evaluate the important indicator of medicinal tablet quality uniformity.Tablet weight (tablet weight, TW) variation is to evaluate medicinal tablet quality
Another important indicator of uniformity.The dosage of medicinal tablet often with " sheet " be unit calculate, TW variation directly affect to
The medicine that the accuracy of pharmaceutical quantities, especially therapeutic index are little, such as: levothyroxine sheet, digoxin, aminophylline tablets etc., relatively
Little TW variation can affect its therapeutic effect and (or) increase the weight of its untoward reaction.Additionally, the disintegration of medicinal tablet checks
All it is loaded into multinational pharmacopeia by the quality control project as drug release in vitro with dissolution test.Due to the disintegrate of tablet and molten
Go out all broken to tablet complexity relevant, sheet tensile strength (tablet radial tensile strength, TRTS)
Variation is also another important indicator evaluating medicinal tablet quality uniformity.Therefore, medicinal tablet quality uniformity is relevant
Factorial analysis is mainly analyzed from the variation of API content, TW variation and TRTS variation etc..
The present invention uses method of analysis of variance, at Fourier transform near infrared spectrum method (Fourier transform near
Infrared spectroscopy, FT-NIRS) and the medicinal tablet uniformity results of chemometric techniques acquisition[1]Base
On plinth, establish a kind of analysis method of medicinal tablet uniform quality sex-related factors, for each producer medicinal tablet production process
The formulation of uniformity controlling scheme provides foundation and reference.
The following is the list of references that inventor is main:
[1] Wu Ruanqi, Dong Yanhong, Fan Qi etc., NIRS method analyzes the uniformity [J] of compound sulfonamide first azoles sheet. and medicine divides
Analysis magazine, 2014,34 (2) 291-296.
Summary of the invention
It is an object of the invention to provide a kind of method analyzing medicinal tablet quality uniformity Related factors.
The present invention is achieved by the following technical solutions:
The method analyzing medicinal tablet uniform quality sex-related factors, is the active medicine measuring every tablet sample respectively
Component content, tablet weight, sheet tensile strength, use variance analysis method calculate respectively each correlative factor batch in, batch between and inter-plant
Variance yields, and compared with near infrared spectrum generalized variance value, in analyzing batch, batch between and inter-plant quality uniformity main
Correlative factor；Specifically include following steps:
(1) tablet samples is collected；
(2) mensuration of tablet samples correlative factor value；
(3) calculate respectively batch internal variance value of each batch, each producer batch between variance yields and the inter-plant of all producers
Variance yields；
(4) in employing Fourier transform near infrared spectrum method (FT-NIRS) and chemometric techniques analysis draw and criticize, criticize
Between and the generalized variance value of inter-plant, its generalized variance value combined with the variance yields in the present invention, analyzes quality uniformity
Correlative factor；
(5) medicinal tablet criticizes the Related factors of interior quality uniformity；
(6) medicinal tablet criticizes the Related factors of a quality uniformity；
(7) Related factors of medicinal tablet inter-plant quality uniformity.
Described medicinal tablet refers to that medicine mixs homogeneously the disc-shaped of compacting or abnormity the consolidating of lamellar with proper auxiliary materials
Body preparation.
The tablet samples collected in described step (1) is from different manufacturers and different batches.
Described step (2) measures every tablet sample API content by high performance liquid chromatography, with g/ sheet and mg/ respectively
Sheet represents；With the TW of the weighed every tablet sample of ten thousand/analytical balance, represent with gram (g)；Survey respectively with tablet hardness instrument
Measuring the radial direction crushing force (F) of every tablet sample, slide gauge measures diameter (D) and the thickness (T) of every tablet sample respectively,
And calculate TRTS value by equation below, represent with MPa (MPa).
In formula, F represents with newton (N)；D and T all represents with millimeter (mm).
In described step (3) each correlative factor batch in, batch between and inter-plant variance yields calculate all use Microsoft
Excel computed in software.
In in described step (5) batch during quality uniformity Related factors, each factory sample near infrared spectrum is criticized interior extensively
The change of right way of conduct difference is found out in criticizing compared with changing with batch internal variance value of the API content of corresponding producer, TW and TRTS respectively
The main associated factors of quality uniformity.
Between described step (6) is criticized during quality uniformity Related factors, wide between each factory sample near infrared spectrum is criticized
The change of right way of conduct difference respectively with the corresponding API content of producer, TW and TRTS batch between compared with variance yields change, between finding out batch
The main associated factors of quality uniformity.
In described step (7) during inter-plant quality uniformity Related factors, by API content, the inter-plant side of TW and TRTS
Difference compared with variance yields between corresponding batch, therefrom finds out the main associated factors of inter-plant quality uniformity respectively.
The present invention analyzes the correlative factor of medicinal tablet quality uniformity.The method can be medicinal tablet production process quality
The formulation of uniformity controlling scheme provides foundation and reference.
Accompanying drawing explanation
Fig. 1 be compound sulfonamide first azoles sheet near infrared spectrum batch in generalized variance value change respectively with SMZ, TMP, TW and
Batch internal variance value change of TRTS compares: A, B and C represent factory A, B and C respectively.
Detailed description of the invention
The present invention is further described with embodiment below in conjunction with the accompanying drawings, and embodiment is the citing of the present invention, should not be seen
Doing is limitation of the invention.
Embodiment
1. sample and information thereof
Collect from 4 producers, 13 crowdes of compound sulfonamide first azoles sheet sample (every 0.4g and TMP Han SMZ of totally 258
80mg), sample message is shown in Table 1.
2. the mensuration of tablet samples correlative factor value
The mensuration of tablet samples active pharmaceutical ingredient content, by " Chinese Pharmacopoeia " (version in 2010) compound sulfonamide first azoles sheet
The high performance liquid chromatography recorded under assay item, and employing chromatographic column Agilent ZORBAX SB-C18 (4.6 × 150mm, 5
μm) (column temperature 30 DEG C), with acetonitrile-water-triethylamine (200: 799: 1) (with glacial acetic acid regulation pH value to 5.9) for flowing phase,
Measure SMZ content and the TMP content of 258 compound sulfonamide first azoles every samples of sheet at 240nm wavelength the most simultaneously.As a result,
SMZ content is 0.3551～0.4385g/ sheet, and TMP content is 72.4～90.2mg/ sheets.
The mensuration of tablet samples tablet weight, uses ten thousand/analytical balance accurately weighed 258 compound sulfonamide first respectively
The weight of every, azoles sheet sample.As a result, surveyed TW is 0.4999～0.5897g.
The mensuration of tablet samples sheet tensile strength, uses tablet hardness instrument to measure 258 compound sulfonamide first azoles sheets respectively
The sheet of every, sample radially crushing force, uses slide gauge to measure diameter and the thickness of every sample respectively, and calculates with formula
The value of every blade tensile strength.As a result, surveyed TRTS is 0.4069～2.1960MPa.
3. the generalized variance value of compound sulfonamide first azoles sheet sample
The uniformity of 4 producers 13 batches totally 258 samples uses FT-NIRS method and chemometric techniques to carry out point
Analysis, in its batch, batch between and the generalized variance value of inter-plant be shown in Table 1.
Table 1 compound sulfonamide first azoles sheet sample message and near infrared spectrum criticize interior, batch between and inter-plant generalized variance value
4. variance analysis
Calculate respectively with method of analysis of variance batch internal variance value of compound sulfonamide first azoles sheet 13 batch sample, each producer batch
Between variance yields and inter-plant variance yields, each correlative factor batch in and batch between variance yields result respectively as shown in table 2 below and table 3,4
The SMZ content of producer's sample, TMP content, the inter-plant variance yields of TW and TRTS, result is followed successively by 0.456 × 10-5(g/tablet
)2、0.567(mg/tablet)2、13.9×10-5(g2) and 72.6 × 10-3(MPa)2。
Table 2 compound sulfonamide first azoles sheet 13 batch sample SMZ content, TMP content, batch internal variance value of TW and TRTS
3 producer's sample SMZ content of table 3 compound sulfonamide first azoles sheet, TMP content, TW and TRTS batch between variance yields
5. medicinal tablet criticizes the analysis of interior quality uniformity correlative factor
From Table 2, it can be seen that each correlative factor of the compound sulfonamide first each batch sample of azoles sheet all exists in various degree
Variation within batch, illustrates that 4 correlative factor variations are all the correlative factors that compound sulfonamide first azoles sheet criticizes interior quality uniformity.
The unit of 4 correlative factors owing to being studied is inconsistent, it is difficult to directly relatively each correlative factor is to compound sulfonamide
First azoles sheet criticizes the influence degree of interior uniformity.For confirming batch main associated factors of interior uniformity, by factory A, B and C in table 1
The near infrared spectrum of (factory D is the most a collection of, therefore is not analyzed) criticize interior generalized variance change respectively with each phase of corresponding producer in table 2
Batch internal variance change of pass factor compares, and sees Fig. 1.Fig. 1 shows, it is TW variation that factory A criticizes the main associated factors of interior uniformity；
Factory B criticizes the main associated factors of interior uniformity and includes the variation of SMZ content, the variation of TMP content and TRTS variation；Factory C criticize interior uniformly
Property main associated factors be TW variation, secondary correlative factor include SMZ content variation and TMP content make a variation.
In batch, quality uniformity Related factors result shows, compound sulfonamide Jia Zuopiange factory criticizes the master of interior uniformity
Wanting correlative factor to differ, it is incomplete same that analysis is probably the production technology of this Pian Ge factory, quality control and GMP performance
Caused.
6. medicinal tablet criticizes an analysis for quality uniformity correlative factor
From table 3 it is observed that each correlative factor of compound sulfonamide Jia Zuopiange factory sample all exists in various degree
Batch variation, illustrates that 4 correlative factor variations are all the correlative factors that compound sulfonamide first azoles sheet criticizes a quality uniformity.
Compound sulfonamide Jia Zuopiange factory sample near infrared spectrum in table 1 is criticized a change of generalized variance value respectively with table
In 3 each correlative factor of corresponding producer batch between the change of variance yields compare as a result, between 3 producer's sample near infrared spectrums criticize
The change of generalized variance value and TW criticize the change of a variance yields and have concordance highly, and TMP content criticizes the change of a variance yields
Change and there is higher concordance, and SMZ content and TRTS to criticize the change concordance of a variance yields the most relatively low.Speculate that each factory criticizes interstitial
The main associated factors of amount uniformity is TW variation.
Between Pi, quality uniformity Related factors result shows, produces the tablet machine work of each batch of compound recipe Sulfamethoxazole sheet
Making the fluctuation of parameter, granulating process parameter etc. causes the batch variation of TW big；And the prescription ratio of TMP is less, cause its content
Batch variation bigger.
7. the analysis of medicinal tablet inter-plant uniform quality sex-related factors
Be can be seen that by inter-plant variance yields, the SMZ content of compound sulfonamide Jia Zuopiange factory sample, TMP content, TW and TRTS
All there is inter-plant variation in various degree, illustrate that 4 correlative factor variations are all compound sulfonamide first azoles sheet inter-plant uniform quality
The correlative factor of property.
As a result, SMZ contains compared with variance yields between the inter-plant variance yields of each correlative factor is criticized accordingly with table 3 respectively
Amount, TMP content and TRTS inter-plant variance yields all and between its batch variance yields suitable, and the inter-plant variance yields of TW is higher than side between its batch
Difference, illustrates that the major measure improving inter-plant uniformity is for reducing TW variation.Due to compound sulfonamide first azoles sheet near infrared spectrum
Analysis result be inter-plant uniformity less than batch between uniformity, can speculate that the main associated factors of inter-plant quality uniformity is that TW becomes
Different.
Inter-plant quality uniformity Related factors result shows: each factory produces the tabletting type of compound sulfonamide first azoles sheet
Number and the fluctuation of running parameter, granulating process parameter etc. cause the bigger inter-plant of TW to make a variation.
8. conclusion
The present invention uses method of analysis of variance to confirm from the variation of SMZ content, the variation of TMP content, TW variation and TRTS variation
Surveyed compound sulfonamide first azoles sheet criticize interior, batch between and the main associated factors of inter-plant quality uniformity (it is equal that each factory criticizes interior quality
The main associated factors of even property differs, and between batch, the main associated factors with inter-plant quality uniformity is tablet weight variation).This knot
Fruit provides foundation for the formulation of compound sulfonamide first azoles sheet production process quality uniformity control program, is also other drug sheet
The uniform quality Journal of Sex Research of agent manufacturer and control provide reference.
Claims (6)
1. the analysis method of a medicinal tablet uniform quality sex-related factors, it is characterised in that: measure every medicine sheet respectively
The active pharmaceutical ingredient content of agent, tablet weight, sheet tensile strength, use variance analysis method to calculate criticizing of each correlative factor respectively
In, batch between and inter-plant variance yields, and compared with near infrared spectrum generalized variance value, in analyzing batch, batch between and inter-plant uniform
Property main associated factors, for medicinal tablet manufacturer quality uniformity research with control provide according to and reference；Specifically
Comprise the following steps:
(1) tablet samples is collected；
(2) mensuration of tablet samples correlative factor value；
(3) calculate respectively batch internal variance value of each batch of each correlative factor, each producer batch between variance yields and all producers
Inter-plant variance yields；
(4) in using Fourier transform near infrared spectrum method (FT-NIRS) and chemometric techniques analysis to draw batch, batch between and
The generalized variance value of inter-plant, combines its generalized variance value with variance yields, analyzes the correlative factor of quality uniformity；
(5) medicinal tablet criticizes the Related factors of interior quality uniformity；
(6) medicinal tablet criticizes the Related factors of a quality uniformity；
(7) Related factors of medicinal tablet inter-plant quality uniformity.
The analysis method of medicinal tablet uniform quality sex-related factors the most according to claim 1, it is characterised in that: described
The mensuration of tablet samples correlative factor value in step (2), uses high performance liquid chromatography, measures the work of every tablet sample respectively
Property content of active component；By ten thousand/analytical balance, the respectively tablet weight of accurately weighed every tablet sample；Use tablet hardness instrument
Measure the radial direction crushing force of every tablet sample respectively, measure diameter and the thickness of every tablet sample with slide gauge respectively,
And calculate its sheet tensile strength value with formula.
The analysis method of medicinal tablet uniform quality sex-related factors the most according to claim 1, it is characterised in that: described
In step (3) each correlative factor batch in, batch between and inter-plant variance yields calculate all use Microsoft Excel computed in software.
The analysis method of medicinal tablet uniform quality sex-related factors the most according to claim 1, it is characterised in that: described
The Related factors of interior quality uniformity criticized by step (5) Chinese medicine tablet, and each factory sample near infrared spectrum is criticized interior broad sense side
The change of difference respectively with the change of batch internal variance value of active pharmaceutical ingredient content, tablet weight and the sheet tensile strength of corresponding producer
Compare, analyze batch main associated factors of interior quality uniformity.
The analysis method of medicinal tablet uniform quality sex-related factors the most according to claim 1, it is characterised in that: described
The Related factors of a quality uniformity criticized by step (6) Chinese medicine tablet, and each factory sample near infrared spectrum is criticized a broad sense side
The change of difference criticizes the change phase of a variance yields with the corresponding active pharmaceutical ingredient content of producer, tablet weight and sheet tensile strength respectively
Compare, analyze the main associated factors of quality uniformity between criticizing.
The analysis method of medicinal tablet uniform quality sex-related factors the most according to claim 1, it is characterised in that: described
The Related factors of step (7) Chinese medicine tablet inter-plant quality uniformity, by the inter-plant variance yields of each correlative factor respectively with
Between corresponding batch, variance yields compares, and therefrom analyzes the main associated factors of inter-plant quality uniformity.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103792205A (en) * | 2014-01-22 | 2014-05-14 | 重庆医科大学 | High-flux near-infrared sensitive fast non-destructive analysis for impurities and tensile strength of tablets |
| CN103808688A (en) * | 2014-01-22 | 2014-05-21 | 重庆医科大学 | Rapid non-destructive detection on quality consistency of finished medicine product by using near-infrared spectroscopy |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103792205A (en) * | 2014-01-22 | 2014-05-14 | 重庆医科大学 | High-flux near-infrared sensitive fast non-destructive analysis for impurities and tensile strength of tablets |
| CN103808688A (en) * | 2014-01-22 | 2014-05-21 | 重庆医科大学 | Rapid non-destructive detection on quality consistency of finished medicine product by using near-infrared spectroscopy |
Non-Patent Citations (4)
| Title |
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| Simultaneous determination of the impurity and radial tensile strength of reduced glutathione tablets by a high selective NIR-PLS method;Juan Li et al.;《Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy》;20140204;第278-284页 * |
| 红外光谱技术在中国酿酒行业中的应用研究进展;邵春甫等;《中国酿造》;20131231;第32卷(第4期);第15-19页 * |
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