CN104666084B - A method of it improves and delays controlled release coat piece dissolution rate stability - Google Patents
A method of it improves and delays controlled release coat piece dissolution rate stability Download PDFInfo
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- CN104666084B CN104666084B CN201410707573.8A CN201410707573A CN104666084B CN 104666084 B CN104666084 B CN 104666084B CN 201410707573 A CN201410707573 A CN 201410707573A CN 104666084 B CN104666084 B CN 104666084B
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Abstract
The present invention provides a kind of methods improving slow controlled release coat piece dissolution rate stability, and when coating agent is organic solvent, the discharge concentration that organic vapor in tail gas is coated by detection changes with time to obtain the Best Times for determining addition coating dry powder；This control method is easy to operate, and as a result accuracy is high, can effectively improve the quality of the pharmaceutical preparations of slow controlled release coat piece, makes it have stable dissolution rate.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, especially a kind of to improve the method for delaying controlled release coat piece dissolution rate stability.
Background technology
Film coating process is widely used in pharmaceutical manufacturing process in recent years, film coating have it is moisture-proof, be protected from light and improve
Appearance, color and taste effect, in addition, film coating can be also used for control drug rate of release, be to prepare sustained release
The processing step of piece or controlled release tablet indispensability.
The common coating material of film coating be generally high-molecular compound (such as hydroxypropyl methyl cellulose (HPMC),
Hydroxypropyl cellulose (PC)) either other coating materials and coating solution solvent is usually purified water or organic solvent.If production
Product are soluble easily in water, then are typically chosen organic solvent as coating agent (such as ethyl alcohol, acetone or isopropanol).
In coating process, usually a certain amount of coating agent is dissolved in coating solvent and forms coating solution.In coating pan
Interior, coating solution is continuously sprayed at after being atomized by spray gun device on solid pharmaceutical preparation label, at the same the solid tablet in coating pan with
It the rotation of coating pan and constantly mixes, hot air tablet in coating pan while, evaporates the coating solution on tablet,
Coating pan is discharged with the tail gas of coating pan in organic solvent, and thin film is formed in tablet surface after coating solution drying.It is preparing
When special sustained release or controlled release tablet, solid pharmaceutical preparation, which may pass through, is repeated several times coating to reach required Dissolution of Tablet quality
Standard.At this point, every time plus before new coating solution, last coating solution needs to parch substantially, after otherwise new coating solution adds,
Can cause to be coated it is uneven, to influence coating quality and dissolution results.Also, it in order to avoid tablet mutually bonds, is wrapping
When clothing liquid will finish, it is also necessary to which the tablet into coating pan is added on a small quantity by the calcium sulphate powders crushed, to prevent to be bonded.
As can be seen that the amount of control coating solution and addition are coated the opportunity of dry powder for product quality in above process
Control is of great significance.In the prior art for the residual quantity of monitoring tablet surface coatings liquid organic solvent, and really
Surely the appropriate time of addition calcium sulphate powders is entirely individual's warp by coating operations personnel all without good control method
It tests.Therefore, obtained product quality especially dissolution performance is extremely unstable, and differences between batches are larger, can not be to producing
Cheng Jinhang quality controls.
Invention content
Technical problem to be solved by the present invention lies in provide a kind of side for improving slow controlled release coat piece dissolution rate stability
Method.
In order to solve the above technical problems, the technical scheme is that：
A method of it improves and delays controlled release coat piece dissolution rate stability, when coating agent is organic solvent, wrapped by detecting
In clothing tail gas the discharge concentration of organic vapor change with time to obtain determine be added coating dry powder it is best when
Between.
Preferably, the method for controlled release coat piece dissolution rate stability is delayed in above-mentioned raising, the specific steps are：
(1) start coating process, scheduled label is added into coating pan, adjust the temperature of coating pan interior air-flow, then
Start to be coated；
(2) after coating starts, timing (for example, every 5-10 seconds) measures and records organic molten in coating pan tail gas
Agent concentration (ppm)；
(3) organic vapor volatile quantity is calculated：It will be under every organic solvent evaporation curve added with solvent from beginning
Area cumulative integral calculate, obtain evaporation total amount；In addition, from starting added with solvent to the total amount of organic solvent evaporating completely
It is to calculate the organic solvent amount evaporated in some specific time on this basis as 100% and account for organic solvent evaporation
The percentage (i.e. evaporativity) of total amount；
(4) there is certain pair in the organic solvent concentration in coating process in tail gas and the degree of drying on coated tablet surface
It should be related to, organic solvent concentration is first raised to a peak value, then gradually declines, but organic solvent is dense after decline a period of time
Degree is held essentially constant, and drops to lower concentration after continuing for some time again, when organic solvent concentration is held essentially constant
Show the surface of solid tablet substantially dry, is the best opportunity of addition coating dry powder at this time；
(5) the organic solvent discharge rate summation in coating process in tail gas was stepped up with the time, can be with by experiment
Determine the correspondence of organic solvent discharge rate summation and the best opportunity of addition coating dry powder.
For different product and different organic solvents, after finding optimal time, it can be used for Instructing manufacture, this side
Method has general applicability.
Preferably, the method for controlled release coat piece dissolution rate stability, the discharge concentration of organic solvent gas are delayed in above-mentioned raising
Assay method be：One continuous sensor for measuring organic vapor is installed in the discharge duct of coating pan, by its with
Digital measuring apparatus is connected, the organic solvent concentration in being vented with this METHOD FOR CONTINUOUS DETERMINATION.
Preferably, the method for controlled release coat piece dissolution rate stability is delayed in above-mentioned raising, when the coating agent is ethyl alcohol, tail gas
The middle total discharge rate of alcohol vapour is 75-85%.Note：From start plus ethyl alcohol to ethyl alcohol evaporating completely total amount as 100%.
Preferably, the method for controlled release coat piece dissolution rate stability is delayed in above-mentioned raising, and the total discharge rate of alcohol vapour is
80 ± 5%.
Preferably, the method for controlled release coat piece dissolution rate stability is delayed in above-mentioned raising, and the coating dry powder is sulfuric acid calcium powder
End.
Beneficial effects of the present invention：
The method of controlled release coat piece dissolution rate stability is delayed in above-mentioned raising, utilizes the concentration of alcohol in tail gas in coating process
Certain correspondence existing for degree of drying with coated tablet surface finds organic vapor concentration by repetition test
The surface of solid tablet substantially dry when reaching specified level is the best opportunity for adding calcium sulphate powders；This controlling party
Method is easy to operate, and as a result accuracy is high, can effectively improve the quality of the pharmaceutical preparations of slow controlled release coat piece, makes it have stable dissolution
Degree.
Description of the drawings
Fig. 1 is ethanol gas concentration measurement chart in embodiment 1；
Fig. 2 is accumulation alcohol gas discharge rate measurement chart in embodiment 1；
Fig. 3 is ethanol gas concentration measurement chart in embodiment 2；
Fig. 4 is accumulation alcohol gas discharge rate measurement chart in embodiment 2.
Specific implementation mode
The following technical solution of the present invention is further described with reference to specific embodiment.
1, the device that assembling measures alcohol vapour first includes following equipment and element：
(1) ethanol sensor, 2 IR of Pdytron
(2) digital measuring instruments, Digital Meter GEFRAN 40
(3) 0.2 micron filters
(4) 0-100 liters/min of gas flowmeter
(5) Tygon hoses
2, ethanol sensor and digital measuring instruments are corrected, and 100% range is ethanol vapor concentration 33000ppm.
3, measuring process：One end of ethanol sensor is connected to plastic flexible pipe the gas outlet of coating pan first,
The other end of sensor is connected a vacuum extractor, to wrap by the pneumatic filter that one 0.2 micron is filled on pipeline
Gas in clothing pot is drawn through sensor.Gas flowmeter is adjusted to 20 liters/min or suitable flow.
4, start coating process, the label of predetermined amount is added into coating pan, adjust the temperature of coating pan interior air-flow, then
Start to be coated.
5, after coating starts, the concentration of alcohol (ppm) in coating pan tail gas was measured and recorded every 5-10 seconds.
6, alcohol vapour volatile quantity is calculated：From start plus ethyl alcohol will be in every ethanol evaporation area under a curve cumulative integral
It calculates, obtains evaporation total amount；In addition, from start plus ethyl alcohol to the total amount of ethyl alcohol evaporating completely be as 100%, on this basis
Calculate the percentage (i.e. evaporativity) that the amount of alcohol evaporated in some specific time accounts for ethanol evaporation total amount.
7, the result shows that, concentration of alcohol and the degree of drying on coated tablet surface in coating process in tail gas exist centainly
Correspondence, concentration of alcohol is first raised to a peak value, then gradually declines, but declines concentration of alcohol base after a period of time
Originally it remains unchanged, continues to drop to very low concentration after one section again.Show solid when concentration of alcohol is held essentially constant constant
The surface of tablet substantially dry is the best opportunity for adding calcium sulphate powders at this time.
Embodiment 1
The solid sustained-release preparation label that specification is 0.625 milligram is added into coating pan, makes solid after adjusting gas flow
Label temperature reaches 42 DEG C, then starts gradually to spray into the advance prepared packet for containing 8% Opadry and alcohol solvent to label
Clothing liquid.Start timing with stopwatch, record start plus coating solution to terminate plus the time of coating solution and add calcium sulphate powders when
Between.Amount to after 32 seconds and 2.26L coating solutions are added.The degree of drying for observing label after coating solution by operator is added, 192
Calcium sulphate powders are added when the second.Be coated the while of starting start with alcohol measurement device to measure the tail gas in coating pan in second
The concentration of alcohol is completed when data of 5 seconds records were until 350 seconds.Experimental result is as depicted in figs. 1 and 2.Experiment shows
The time of best addition calcium sulphate powders be the total discharge rate of ethyl alcohol up to 81% when.
Embodiment 2
The solid sustained-release preparation label that specification is 1.25 milligrams is added into coating pan, makes solid piece after adjusting gas flow
Core temperature reaches 42 DEG C, then starts gradually to spray into the advance prepared packet for containing 8% Opadry and alcohol solvent to label
Clothing liquid.Start timing with stopwatch, record start plus coating solution to terminate plus the time of coating solution and add calcium sulphate powders when
Between.Amount to after 37 seconds and 2.46L coating solutions are added.The degree of drying for observing label after coating solution by operator is added, 200
Calcium sulphate powders are added when the second.Be coated the while of starting start with alcohol measurement device to measure the tail gas in coating pan in second
The concentration of alcohol is completed when data of 5-10 seconds records were until 420 seconds.Experimental result is as shown in Figure 3 and Figure 4.Test table
It is bright, the best time for adding calcium sulphate powders be the total discharge rate of ethyl alcohol up to 79% when.
Embodiment 3
The solid sustained-release preparation label that piece weight is 300 milligrams is being added into coating pan, is making solid after adjusting gas flow
Label temperature reaches 42 DEG C, then starts gradually to spray into the advance prepared packet for containing 8% Opadry and alcohol solvent to label
Clothing liquid.Start timing with stopwatch, record start plus coating solution to terminate plus the time of coating solution and add calcium sulphate powders when
Between.With thering is tablet adhesion phenomenon, prepared coating tablet to there is about 10% surface to have in coating process when experiential operating method
Crackle and breakage.There is not adhesion phenomenon, prepared coating tablet surface using coating process tablet after the method for the present invention
It is intact, without breakage.
Embodiment 4
The solid sustained-release preparation label that piece weight is 300 milligrams is being added into coating pan, is making solid after adjusting gas flow
Label temperature reaches 42 DEG C, then starts gradually to spray into the advance prepared packet for containing 8% Opadry and alcohol solvent to label
Clothing liquid.Start timing with stopwatch, record start plus coating solution to terminate plus the time of coating solution and add calcium sulphate powders when
Between.There is exceeded phenomenon with the dissolution rate of coated product when experiential operating method.Using coating process piece after the method for the present invention
Agent dissolution rate meets quality standard, the results are shown in Table 1.
Dissolution results compare when 1 distinct methods of table
In above-described embodiment 1-4, the prescription of the solid sustained-release preparation label see the table below 2.
Table 2
| Effective ingredient | Parts by weight |
| Lactose | 100.0 part |
| Microcrystalline cellulose | 100.0 part |
| Povidone | 50.0 parts |
| Croscarmellose sodium | 30.0 parts |
| Superfine silica gel powder | 20.0 parts |
Above-mentioned the retouching in detail to a kind of method progress improving slow controlled release coat piece dissolution rate stability with reference to embodiment
It states, is illustrative without being restrictive, several embodiments can be enumerated according to limited range, therefore do not departing from this
Change and modification under invention general plotting should belong within protection scope of the present invention.
Claims (4)
1. a kind of improving the method for delaying controlled release coat piece dissolution rate stability, it is characterised in that：When coating agent is organic solvent, lead to
The discharge concentration for crossing organic vapor in detection coating tail gas changes with time to show that determining be added is coated dry powder
Best Times, the specific steps are：
(1) start coating process, scheduled label is added into coating pan, adjust the temperature of coating pan interior air-flow, then start
Coating；
(2) after coating starts, the organic solvent concentration in Timing measurement and record coating pan tail gas；
(3) organic vapor volatile quantity is calculated：From starting added with solvent by the face under every organic solvent evaporation curve
Accumulation product integral and calculating, obtains evaporation total amount；In addition, from starting to be to make added with the total amount of solvent to organic solvent evaporating completely
It is 100%, calculates the organic solvent amount evaporated in some specific time on this basis and account for organic solvent evaporation total amount
Percentage；
(4) with the degree of drying on coated tablet surface there is certain corresponding pass in the organic solvent concentration in coating process in tail gas
System, organic solvent concentration are first raised to a peak value, then gradually decline, but decline organic solvent concentration base after a period of time
Originally it remains unchanged, drops to lower concentration after continuing for some time again, show when organic solvent concentration is held essentially constant
The surface of solid tablet substantially dry is the best opportunity of addition coating dry powder at this time；
(5) the organic solvent discharge rate summation in coating process in tail gas was stepped up with the time, passed through experiment, it may be determined that
The correspondence of organic solvent discharge rate summation and the best opportunity of addition coating dry powder.
2. according to claim 1 improve the method for delaying controlled release coat piece dissolution rate stability, it is characterised in that：It is organic molten
The assay method of the discharge concentration of agent gas is：One continuous measurement organic vapor is installed in the discharge duct of coating pan
Sensor, it is connected with digital measuring apparatus, with this METHOD FOR CONTINUOUS DETERMINATION be vented in organic solvent concentration.
3. according to claim 1 improve the method for delaying controlled release coat piece dissolution rate stability, it is characterised in that：The packet
When clothing agent is ethyl alcohol, the total discharge rate of alcohol vapour is 75-85% in tail gas.
4. according to claim 1 improve the method for delaying controlled release coat piece dissolution rate stability, it is characterised in that：The packet
Clothing dry powder is calcium sulphate powders.
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| CN201410707573.8A CN104666084B (en) | 2014-11-27 | 2014-11-27 | A method of it improves and delays controlled release coat piece dissolution rate stability |
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| CN104666084B true CN104666084B (en) | 2018-07-13 |
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Citations (5)
| 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 |
| 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 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030096001A1 (en) * | 2000-06-06 | 2003-05-22 | Cherukuri S. Rao | Encapsulation products and method of controlled release of fluoxetine or mesalamine |
-
2014
- 2014-11-27 CN CN201410707573.8A patent/CN104666084B/en active Active
Patent Citations (5)
| 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 |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| 二甲双胍片的生产工艺的研究;赵阳;《中国优秀硕士学文论文全文数据库》;20071231(第5期);第37页 * |
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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. |