CN104666084A - Slow and controlled release coating tablet dissolution degree stability improving method - Google Patents
Slow and controlled release coating tablet dissolution degree stability improving method Download PDFInfo
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- CN104666084A CN104666084A CN201410707573.8A CN201410707573A CN104666084A CN 104666084 A CN104666084 A CN 104666084A CN 201410707573 A CN201410707573 A CN 201410707573A CN 104666084 A CN104666084 A CN 104666084A
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Abstract
The invention provides a slow and controlled release coating tablet dissolution degree stability improving method. When the coating agent is of organic solvent, the optimal time for adding coating dry powder can be acquired by detecting the change of the emission concentration of organic solvent vapor of the exhausted gas of a coating machine with the time. The method is convenient to operate, the accuracy of the result is high, the preparation quality of slow and controlled release coating tablets can be improved effectively, and the stable solution degree is provided.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, especially a kind of method improving slow controlled release coat sheet dissolution stability.
Background technology
Film coating process is widely used in pharmaceutical manufacturing process in recent years, film coating has the effect of protection against the tide, the outward appearance of lucifuge and improvement, color and taste, in addition, film coating can also be used for the rate of release controlling medicine, is the processing step of preparation slow releasing tablet or controlled release tablet indispensability.
The coating material that film coating is conventional is generally macromolecular compound (such as hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (PC)) or other coating materials, and coating solution solvent is generally purified water or organic solvent.As fruit product is soluble in water, then generally select organic solvent as coating materials (such as ethanol, acetone or isopropyl alcohol).
In coating process, usually a certain amount of coating materials is dissolved in coating solvent and forms coating solution.In coating pan, coating solution is sprinkled upon on solid preparation label by continuous spraying after spray gun device atomization, solid tablet simultaneously in coating pan constantly mixes along with the rotation of coating pan, by the coating solution evaporation on tablet while hot air tablet in coating pan, organic solvent, along with the tail gas discharge coating pan of coating pan, forms thin film in tablet surface after coating solution drying.When preparing special slow release or controlled release tablet, solid preparation may through repeatedly repeating coating to reach required Dissolution of Tablet quality standard.Now, before adding new coating solution, last coating solution needs substantially to parch at every turn, otherwise after newly coating solution adds, coating can be caused uneven, thus affect coating quality and dissolution results.Further, in order to avoid tablet bonds mutually, when coating solution is about to finish, also need to add a small amount of calcium sulphate powders through pulverizing to the tablet in coating pan, bonding to stop.
Can find out, the amount controlling coating solution in above process and the opportunity of adding coating dry powder are of great significance for control of product quality.For the residual quantity of monitoring tablet surface coatings liquid organic solvent in prior art, and determining that the appropriate time adding calcium sulphate powders does not all have good control method, is the personal experience relying on coating operations personnel completely.Therefore, the product quality obtained is dissolution performance extremely unstable particularly, and differences between batches are comparatively large, can not carry out quality control to production process.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of method improving slow controlled release coat sheet dissolution stability.
For solving the problems of the technologies described above, technical scheme of the present invention is:
Improve a method for slow controlled release coat sheet dissolution stability, when coating materials is organic solvent, by the discharge concentration that detects organic vapor in seed-coating machine tail gas over time thus draw the Best Times determining to add coating dry powder.
Preferably, the method for controlled release coat sheet dissolution stability is delayed in above-mentioned raising, and concrete steps are:
(1) start coating process, in coating pan, add predetermined label, regulate the temperature of air-flow in coating pan, then start coating;
(2) after coating starts, regularly (such as, every 5-10 second) measures and organic solvent concentration (ppm) in record coating pan tail gas;
(3) calculate organic vapor volatile quantity: from add organic solvent and will calculate at every bar organic solvent evaporation area under a curve cumulative integral, obtain evaporating total amount; In addition, to add organic solvent to the total amount that organic solvent evaporates completely be as 100%, calculate the percentage ratio (i.e. evaporativity) that the organic solvent amount of having evaporated at certain special time accounts for organic solvent evaporation total amount on this basis;
(4) there is certain corresponding relation in the degree of drying on the organic solvent concentration in coating process in tail gas and coated tablet surface, first organic solvent concentration is elevated to a peak value, then progressively decline, but organic solvent concentration remains unchanged substantially after a period of time that declines, lower concentration is dropped to again after continuing for some time, showing the surface substantially dry of solid tablet when organic solvent concentration remains unchanged substantially, is now the best opportunity of adding coating dry powder;
(5) the organic solvent output summation in coating process in tail gas progressively increases along with the time, by experiment, can determine the corresponding relation of the best opportunity of organic solvent output summation and interpolation coating dry powder.
For different product and different organic solvents, after finding optimal time, may be used for Instructing manufacture, the method has general applicability.
Preferably, the method of controlled release coat sheet dissolution stability is delayed in above-mentioned raising, the assay method of the discharge concentration of organic solvent gas is: the sensor installing a continuous measurement organic vapor in the discharge duct of coating pan, it is connected with digital measuring apparatus, with the organic solvent concentration in this METHOD FOR CONTINUOUS DETERMINATION aerofluxus.
Preferably, the method for controlled release coat sheet dissolution stability is delayed in above-mentioned raising, and when described coating materials is ethanol, in tail gas, alcohol vapour total output is 75-85%.Note: from add total amount that ethanol evaporates completely to ethanol as 100%.
Preferably, the method for controlled release coat sheet dissolution stability is delayed in above-mentioned raising, and described alcohol vapour total output is 80 ± 5%.
Preferably, the method for controlled release coat sheet dissolution stability is delayed in above-mentioned raising, and described coating dry powder is calcium sulphate powders.
Beneficial effect of the present invention:
The method of controlled release coat sheet dissolution stability is delayed in above-mentioned raising, utilize certain corresponding relation that the degree of drying on the concentration of alcohol in coating process in tail gas and coated tablet surface exists, the surface substantially dry of solid tablet when finding that organic solvent steam concentration reaches specified level by repetition test is the best opportunity of adding calcium sulphate powders; This control method is easy and simple to handle, and result accuracy is high, effectively can improve the quality of the pharmaceutical preparations of slow controlled release coat sheet, make it have stable dissolution.
Accompanying drawing explanation
Fig. 1 is ethanol gas concentration mensuration figure in embodiment 1;
Fig. 2 is accumulation alcohol gas output mensuration figure in embodiment 1;
Fig. 3 is ethanol gas concentration mensuration figure in embodiment 2;
Fig. 4 is accumulation alcohol gas output mensuration figure in embodiment 2.
Detailed description of the invention
Below in conjunction with specific embodiment, the following technical scheme of the present invention is further described.
1, first the device of assembling measurement alcohol vapour comprises following equipment and element:
(1) ethanol sensor, Pdytron 2 IR
(2) digital measuring instruments, Digital Meter GEFRAN 40
(3) 0.2 micron filters
(4) gas flowmeter 0-100 liter/min
(5) Tygon flexible pipe
2, ethanol sensor and digital measuring instruments are through overcorrect, and 100% range is ethanol vapor concentration 33000ppm.
3, measuring process: the gas outlet first with plastic flexible pipe, one end of ethanol sensor being connected to coating pan, pipeline fills the pneumatic filter of 0.2 micron, the other end of sensor is connected a vacuum extractor, the gas in coating pan is drawn through sensor.Gas flowmeter is adjusted to 20 liters/min or suitable flow.
4, start coating process, in coating pan, add the label of scheduled volume, regulate the temperature of air-flow in coating pan, then start coating.
5, after coating starts, measure and record the concentration of alcohol (ppm) in coating pan tail gas second every 5-10.
6, calculate alcohol vapour volatile quantity: from add ethanol and will calculate at every bar ethanol evaporation area under a curve cumulative integral, obtain evaporating total amount; In addition, to add ethanol to the total amount that ethanol evaporates completely be as 100%, calculate the percentage ratio (i.e. evaporativity) that the amount of alcohol of having evaporated at certain special time accounts for ethanol evaporation total amount on this basis.
7, result shows, there is certain corresponding relation in the degree of drying on the concentration of alcohol in coating process in tail gas and coated tablet surface, first concentration of alcohol is elevated to a peak value, then progressively decline, but after a period of time that declines, concentration of alcohol remains unchanged substantially, drops to very low concentration again after continuing one section.Showing the surface substantially dry of solid tablet when concentration of alcohol keeps invariable substantially, is now the best opportunity of adding calcium sulphate powders.
Embodiment 1
In coating pan, add the solid sustained-release preparation label that specification is 0.625 milligram, after adjustment gas flow, make solid label temperature reach 42 DEG C, then start to spray into label the coating solution containing 8% Opadry and alcohol solvent prepared in advance gradually.Start timing with stopwatch, record starts to add coating solution to terminating to add the time of coating solution and adding the time of calcium sulphate powders.2.26L coating solution is added altogether afterwards at 32 seconds.Observed the degree of drying of label after adding coating solution by operator, 192 seconds time, add calcium sulphate powders.While coating starts, start with alcohol measurement device the concentration measuring ethanol in the tail gas in coating pan, every 5 seconds record one secondary data until 350 seconds time complete.Experimental result as depicted in figs. 1 and 2.Experiment shows, the best time of adding calcium sulphate powders is when total ethanol output reaching 81%.
Embodiment 2
In coating pan, add the solid sustained-release preparation label that specification is 1.25 milligrams, after adjustment gas flow, make solid label temperature reach 42 DEG C, then start to spray into label the coating solution containing 8% Opadry and alcohol solvent prepared in advance gradually.Start timing with stopwatch, record starts to add coating solution to terminating to add the time of coating solution and adding the time of calcium sulphate powders.2.46L coating solution is added altogether afterwards at 37 seconds.Observed the degree of drying of label after adding coating solution by operator, 200 seconds time, add calcium sulphate powders.While coating starts, start with alcohol measurement device the concentration measuring ethanol in the tail gas in coating pan, every 5-10 record a secondary data second until 420 seconds time complete.Experimental result as shown in Figure 3 and Figure 4.Experiment shows, the best time of adding calcium sulphate powders is when total ethanol output reaching 79%.
Embodiment 3
Adding the solid sustained-release preparation label that sheet is heavily 300 milligrams in coating pan, after adjustment gas flow, making solid label temperature reach 42 DEG C, then starting to spray into label the coating solution containing 8% Opadry and alcohol solvent prepared in advance gradually.Start timing with stopwatch, record starts to add coating solution to terminating to add the time of coating solution and adding the time of calcium sulphate powders.Have tablet adhesion phenomenon with in coating process during experiential operating method, prepared coated tablet has the surface of about 10% to have crackle and breakage.After applying method of the present invention not there is adhesion phenomenon in coating process tablet, and prepared coated tablet surface is intact, does not have breakage.
Embodiment 4
Adding the solid sustained-release preparation label that sheet is heavily 300 milligrams in coating pan, after adjustment gas flow, making solid label temperature reach 42 DEG C, then starting to spray into label the coating solution containing 8% Opadry and alcohol solvent prepared in advance gradually.Start timing with stopwatch, record starts to add coating solution to terminating to add the time of coating solution and adding the time of calcium sulphate powders.The phenomenon that exceeds standard is there is with the dissolution of coated product during experiential operating method.After applying method of the present invention, coating process Dissolution of Tablet meets quality standard, the results are shown in Table 1.
Dissolution results contrast during table 1 distinct methods
In above-described embodiment 1-4, the prescription of described solid sustained-release preparation label sees the following form 2.
Table 2
| Active ingredient | Parts by weight |
| Lactose | 100.0 part |
| Microcrystalline Cellulose | 100.0 part |
| Polyvidone | 50.0 parts |
| Cross-linking sodium carboxymethyl cellulose | 30.0 parts |
| Micropowder silica gel | 20.0 parts |
Above-mentioned detailed description of a kind of this method improving slow controlled release coat sheet dissolution stability being carried out with reference to embodiment; illustrative instead of determinate; several embodiments can be listed according to institute's limited range; therefore in the change do not departed under general plotting of the present invention and amendment, should belong within protection scope of the present invention.
Claims (5)
1. one kind is improved the method for slow controlled release coat sheet dissolution stability, it is characterized in that: when coating materials is organic solvent, by the discharge concentration that detects organic vapor in seed-coating machine tail gas over time thus draw the Best Times determining to add coating dry powder.
2. the method for controlled release coat sheet dissolution stability is delayed in raising according to claim 1, it is characterized in that: concrete steps are:
(1) start coating process, in coating pan, add predetermined label, regulate the temperature of air-flow in coating pan, then start coating;
(2) after coating starts, Timing measurement and the organic solvent concentration recorded in coating pan tail gas;
(3) calculate organic vapor volatile quantity: from add organic solvent and will calculate at every bar organic solvent evaporation area under a curve cumulative integral, obtain evaporating total amount; In addition, to add organic solvent to the total amount that organic solvent evaporates completely be as 100%, calculate the percentage ratio that the organic solvent amount of having evaporated at certain special time accounts for organic solvent evaporation total amount on this basis;
(4) there is certain corresponding relation in the degree of drying on the organic solvent concentration in coating process in tail gas and coated tablet surface, first organic solvent concentration is elevated to a peak value, then progressively decline, but organic solvent concentration remains unchanged substantially after a period of time that declines, lower concentration is dropped to again after continuing for some time, showing the surface substantially dry of solid tablet when organic solvent concentration remains unchanged substantially, is now the best opportunity of adding coating dry powder;
(5) the organic solvent output summation in coating process in tail gas progressively increases along with the time, by experiment, can determine the corresponding relation of the best opportunity of organic solvent output summation and interpolation coating dry powder.
3. the method for controlled release coat sheet dissolution stability is delayed in raising according to claim 1, it is characterized in that: the assay method of the discharge concentration of organic solvent gas is: the sensor installing a continuous measurement organic vapor in the discharge duct of coating pan, it is connected with digital measuring apparatus, with the organic solvent concentration in this METHOD FOR CONTINUOUS DETERMINATION aerofluxus.
4. the method for controlled release coat sheet dissolution stability is delayed in raising according to claim 1, it is characterized in that: when described coating materials is ethanol, and in tail gas, alcohol vapour total output is 75-85%.
5. the method for controlled release coat sheet dissolution stability is delayed in raising according to claim 1, it is characterized in that: described coating dry powder is calcium sulphate powders.
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| CN87103409A (en) * | 1986-04-11 | 1987-12-09 | Basf公司 | Preparation of solid pharmaceutical dosage forms |
| AU2594688A (en) * | 1987-11-27 | 1989-06-01 | Dow Chemical Company, The | A process for coating a tablet composition |
| US20030096001A1 (en) * | 2000-06-06 | 2003-05-22 | Cherukuri S. Rao | Encapsulation products and method of controlled release of fluoxetine or mesalamine |
| WO2005102269A2 (en) * | 2004-04-21 | 2005-11-03 | Basf Aktiengesellschaft | An amine drug-containing slow-release granule preparation based on particles with a coating layer and the corresponding method of production |
| CN101536992A (en) * | 2008-03-17 | 2009-09-23 | 天津瑞普生物技术集团有限公司 | Livestock cefquinome colon-targeted pills and preparation method thereof |
| CN103091461A (en) * | 2013-01-15 | 2013-05-08 | 广东电网公司电力科学研究院 | System and method of mercury re-release characteristic experiment in wet flue gas desulfurization slurry |
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2014
- 2014-11-27 CN CN201410707573.8A patent/CN104666084B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87103409A (en) * | 1986-04-11 | 1987-12-09 | Basf公司 | Preparation of solid pharmaceutical dosage forms |
| AU2594688A (en) * | 1987-11-27 | 1989-06-01 | Dow Chemical Company, The | A process for coating a tablet composition |
| US20030096001A1 (en) * | 2000-06-06 | 2003-05-22 | Cherukuri S. Rao | Encapsulation products and method of controlled release of fluoxetine or mesalamine |
| WO2005102269A2 (en) * | 2004-04-21 | 2005-11-03 | Basf Aktiengesellschaft | An amine drug-containing slow-release granule preparation based on particles with a coating layer and the corresponding method of production |
| CN101536992A (en) * | 2008-03-17 | 2009-09-23 | 天津瑞普生物技术集团有限公司 | Livestock cefquinome colon-targeted pills and preparation method thereof |
| CN103091461A (en) * | 2013-01-15 | 2013-05-08 | 广东电网公司电力科学研究院 | System and method of mercury re-release characteristic experiment in wet flue gas desulfurization slurry |
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Effective date of registration: 20191017 Address after: 300457 West Zone, 185 West Avenue, 401-420 West South Street, Binhai New Area Economic and Technological Development Zone, Tianjin, four Patentee after: Kansino Biological Co., Ltd. Address before: 601 room 2, building 276, No. 300457 Huang Hai Road, Tianjin economic and Technological Development Zone, Binhai New Area, Tianjin, China Patentee before: Tianjin Kunjian Biological Pharmaceutical Co., Ltd. |
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