CN101584674A - Venlafaxine hydrochloride sustained-release tablet preparation and preparation method thereof - Google Patents
Venlafaxine hydrochloride sustained-release tablet preparation and preparation method thereof Download PDFInfo
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- CN101584674A CN101584674A CNA2008100377572A CN200810037757A CN101584674A CN 101584674 A CN101584674 A CN 101584674A CN A2008100377572 A CNA2008100377572 A CN A2008100377572A CN 200810037757 A CN200810037757 A CN 200810037757A CN 101584674 A CN101584674 A CN 101584674A
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Abstract
The invention discloses a venlafaxine hydrochloride sustained-release tablet preparation which comprises venlafaxine hydrochloride, framework material, diluent, lubricant, adhesive and coating material. The experiments demonstrate that the venlafaxine hydrochloride sustained-release tablet achieves better sustained-release effect, can reduce the dosing frequency and is convenient for the patients to use. The invention also provides a preparation method thereof.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of novel antidepressant venlafaxine hydrochloride sustained-release tablet preparation and preparation method thereof.
Background technology
Venlafaxine is a novel phenylethylamine derivative.Its mechanism of action is different from tricyclic antidepressant and newer selective serotonin reuptake inhibitor, it is by suppressing norepinephrine and serotonin reuptake transporter and antidepressant effect being brought into play in the weak inhibition of dopamine reuptake, to monoamine oxidase, MAO unrestraint effect, can wait receptor not have affinity with cholinergic, histaminergic, adrenal gland, thereby the not untoward reaction such as calmness, xerostomia, constipation, urine retention and blurred vision relevant with these receptors.Venlafaxine is a kind of rapid-action, the better tolerance in the world today, short-term and all good novel antidepressant of long-term treatment curative effect.
Though VENLAFAXINE HCL determined curative effect, but metabolism is fast in vivo owing to this medicine, and conventional tablet or capsule specification can only be 25mg when using clinically, and during clinical use, the onset dosage of every day then is 75mg, can make patient's medicining times increase of every day like this.Produce shortcomings such as blood concentration fluctuation is big, side effect is big thus.In order to improve curative effect of medication, reduce administration number of times, alleviate drug side effect, must improve the dosage form of VENLAFAXINE HCL preparation.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, and the research design venlafaxine hydrochloride sustained-release tablet preparation makes it reach slow release effect preferably, and the effectively lasting time is long, and gastrointestinal side effect is littler.
The invention provides a kind of venlafaxine hydrochloride sustained-release tablet preparation.It is to be made by active substance VENLAFAXINE HCL and pharmaceutic adjuvant.
Venlafaxine hydrochloride sustained-release tablet preparation of the present invention is made up of following materials of weight proportions:
75 parts of VENLAFAXINE HCL
Framework material 1-250 part
Diluent 1-250 part
Lubricant 0-10 part
Binding agent 0-20 part
Coating material 0-50 part
Wherein, described framework material is slow controlled release matrix material, comprises one or more the mixture in hypromellose, alginic acid and derivant thereof, sodium carboxymethyl cellulose, carbomer, the ethyl cellulose etc.
Described coating material comprises one or more mixture in ethyl cellulose and derivant thereof, EUDRAGIT NE 30 D EUDRAGIT NE 30D, the ethylene-vinyl acetate copolymer etc. for slow release controlling coating material.
Described diluent is one or more the mixture in microcrystalline Cellulose, pregelatinized Starch, starch, the lactose etc.
Described binding agent is one or more the mixture among polyvinylpyrrolidone, ethyl cellulose, hydroxypropyl emthylcellulose, the HPMC etc.
Described lubricant is one or more the mixture in silicon dioxide, the magnesium stearate etc.
Another object of the present invention provides the preparation method of above-mentioned venlafaxine hydrochloride sustained-release tablet.This method comprises following 3 schemes:
1, adopt the direct compression process preparation:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent, lubricant are sieved respectively, mix homogeneously obtains mixed powder then;
B. with the mixed powder direct compression, obtain label;
C. will delay in the alcoholic solution that release controlling coating material is dissolved in water or 80% left and right sides concentration, make concentration and be about 15% coating solution, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution;
D. with label with above-mentioned hybrid packet clothing liquid coating;
E. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
2, adopt the preparation of dry granulation method:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent are sieved respectively, mix homogeneously obtains mixed powder then;
B. with mixed powder dry granulation (as adopting that double compression, dry powder extruding are granulated etc.), and add lubricant, mix homogeneously obtains granule;
C. with the granule tabletting, obtain label;
D. will delay in the alcoholic solution that release controlling coating material is dissolved in water or (55%～95%) concentration, make the coating solution of concentration, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution for (8%～35%);
E. with label with above-mentioned hybrid packet clothing liquid coating;
F. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
3, adopt the wet granulation process preparation:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent are sieved respectively, mix homogeneously obtains mixed powder then;
B. mixed powder is carried out wet granulation with 10% polyethylene pyrrole Lip river alkane ketone alcoholic solution as binding agent, after wet granular oven dry (30 ℃～85 ℃), add lubricant, mix homogeneously obtains granule;
C. with the granule tabletting, obtain label;
D. will delay in the alcoholic solution that release controlling coating material is dissolved in water or (55%～95%) concentration, make the coating solution of concentration, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution for (8%～35%);
E. with label with above-mentioned hybrid packet clothing liquid coating;
F. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
Effect test of the present invention:
Venlafaxine hydrochloride sustained-release capsule (the Efexor XR that venlafaxine hydrochloride sustained-release tablet release in vitro of the present invention is produced with U.S. Wyeth
) as the standard reference preparation.The stripping curve that obtains is as shown in Figure 1:
Similar factors is calculated: the comparison of sustained-release preparation release profiles can reflect the influence of factors such as same preparation prescription, technology and release conditions to the preparation drug release behavior, also can reflect between different preparations the difference of (as reference preparation and be subjected to test preparation) drug release behavior.The release profiles similarity of bibliographical information method relatively is a lot, and this research adopts U.S. FDA to recommend the similar factors (f that uses
2) method, its computing formula is as follows:
f
2＝50log[[1+1/n∑W
t(R
t-T
t)
2]
-0.5×100]
In the formula, R
tAnd T
tBe meant that respectively two kinds of preparations are in the release during in t under the same release conditions; N is the sum of sample point; W
tBe the weight coefficient (W in this test that selects according to actual needs
t=1.0).
f
2Result of calculation≤100.When two release curves fit like a glove, f
2Be 100; When two curve differences increase, f
2Value reduces.This research regulation f
2Value can think between 65～100 that two kinds of preparations are in same release condition or same prescription preparation release indifference in different release conditions.
The prescription and the technological factor that influence the sustained-release tablets release behavior are a lot, for simplifying experiment, this research is under the condition of fixing coating technological parameter, according to the characteristics of slow releasing tablet, label and clothing film prescription, related process and external release condition are investigated the influence of venlafaxine hydrochloride sustained-release tablet drug release behavior.Investigate in the experiment in factor, respectively with the different prescriptions of each factor the 2nd, 4,8,12,24h is as sample point, calculates the cumulative release percentage rate of medicine, adopts the similar factors method to judge, to investigate the influence of different factors to drug release behavior.
Fixed art for coating parameter is in the experiment: sheet bed weight 200g; Coating pan diameter 20cm; The coating pan rotating speed is 25rpm; Vertical dip angle is 30 ℃; About 25 ℃ of sheet bed tempertaure; The coating solution input speed is 7ml/min; Pressure is 6～8atm; Till the weightening finish of label outer coatings film reaches pre-provisioning request.On the basis that factor is investigated, with reference to the release in vitro standard of import slow releasing capsule: every of this product 2,4,8,12, the stripping quantity of 24h is respectively below 30% of corresponding labelled amount, 30～55%, 55～80%, more than 65～90% and 80%.
Formulating test of the present invention:
The inventor thinks, slow releasing tablet is discharged the bigger factor of influence mainly contain three: the consumption of the viscosity of HPMC, consumption and coating membrane You Teqi.Therefore, formulating is with three levels
Be respectively:
A (viscosity of HPMC): K4M, K15M, K100M;
B (consumption of HPMC): prescription consumption 20%, 30%, 40%
C (consumption of coating membrane You Teqi): coating amount: 1%, 1.5%, 3%
Release profiles with venlafaxine hydrochloride sustained-release tablet release in vitro curve and import preparation " Efexor XR " compares, and adopts similar factors f
2Judge.
Make three factors, three horizontal quadrature EXPERIMENTAL DESIGN, the time, the result showed, each factor to the size sequence of index influence is: the strange NE 30D of You Te label coating has the greatest impact to the release of whole process, according to f
2Similar factors judges that select optimum formula to be: HPMC selects K100M, and the HPMC consumption is to account for 40% of recipe quantity, and the weightening finish of label coating is about 1.5%.
The same Efexor XR of venlafaxine hydrochloride sustained-release tablet provided by the invention
Relatively, the similar factors f that obtains
2Value can reach more than 90, illustrates that venlafaxine hydrochloride sustained-release tablet provided by the invention reaches good slow release effect.
Description of drawings
Venlafaxine hydrochloride sustained-release capsule (the Efexor XR that Fig. 1 venlafaxine hydrochloride sustained-release tablet release in vitro of the present invention is produced with U.S. Wyeth
) stripping curve that obtains as the standard reference preparation.
This stripping curve is an abscissa with the time (unit: hour), is vertical coordinate with the dissolution, weighs the venlafaxine hydrochloride sustained-release capsule (Efexor XR that venlafaxine hydrochloride sustained-release tablet in this invention (among the figure with ● expression) is produced with U.S. Wyeth
) the release in vitro curve difference of (among the figure with ▲ expression).
The specific embodiment:
Following example will the present invention is further elaborated, but do not limit content of the present invention.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: EUDRAGIT NE 30 D EUDRAGIT NE 30D aqueous dispersion
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, direct compression, the above-mentioned coating solution coating of reuse, and add Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: EUDRAGIT NE 30 D EUDRAGIT NE 30D aqueous dispersion
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, dry method system 16 order grains, tabletting, the above-mentioned coating solution coating of reuse, and add an amount of Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: EUDRAGIT NE 30 D EUDRAGIT NE 30D aqueous dispersion
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, wet method system 16 order grains, oven dry adds the recipe quantity magnesium stearate, mixing, tabletting, the above-mentioned coating solution coating of reuse, and add Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: EUDRAGIT NE 30 D EUDRAGIT NE 30D aqueous dispersion
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, wet method system 16 order grains, oven dry adds the recipe quantity magnesium stearate, mixing, tabletting, the above-mentioned coating solution coating of reuse, and add Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: ethyl cellulose
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, wet method system 16 order grains, oven dry adds the recipe quantity magnesium stearate, mixing, tabletting, the above-mentioned coating solution coating of reuse, and add an amount of Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Tablet formulation: (making 1000, every hydrochloric venlafaxine 75mg)
Coating solution: ethylene-vinyl acetate copolymer
Preparation technology: with above former auxilliary 80 mesh sieves of crossing respectively, mix homogeneously then, wet method system 16 order grains, oven dry adds the recipe quantity magnesium stearate, mixing, tabletting, the above-mentioned coating solution coating of reuse, and add an amount of Pulvis Talci.The finished product that has wrapped clothing is placed 40 ℃ of insulations to get final product in 24 hours.
Claims (7)
1, a kind of venlafaxine hydrochloride sustained-release tablet preparation is characterized in that said preparation is made up of following materials of weight proportions:
75 parts of VENLAFAXINE HCL
Framework material 1-250 part
Diluent 1-250 part
Lubricant 0-10 part
Binding agent 0-20 part
Coating material 0-50 part.
2, venlafaxine hydrochloride sustained-release tablet preparation according to claim 1, it is characterized in that described framework material for slow controlled release matrix material, comprises one or more mixture in hypromellose, alginic acid and derivant thereof, sodium carboxymethyl cellulose, carbomer or the ethyl cellulose.
3, venlafaxine hydrochloride sustained-release tablet preparation according to claim 1, it is characterized in that described coating material for slow release controlling coating material, comprises one or more mixture in ethyl cellulose and derivant thereof, EUDRAGIT NE 30 D EUDRAGIT NE 30D or the ethylene-vinyl acetate copolymer.
4, venlafaxine hydrochloride sustained-release tablet preparation according to claim 1 is characterized in that described diluent is one or more mixture in microcrystalline Cellulose, pregelatinized Starch, starch or the lactose; Described binding agent is one or more mixture among polyvinylpyrrolidone, ethyl cellulose, hydroxypropyl emthylcellulose or the HPMC; Described lubricant is one or more mixture in silicon dioxide or the magnesium stearate.
5, a kind of preparation method of venlafaxine hydrochloride sustained-release tablet preparation according to claim 1 is characterized in that this method adopts the direct compression process preparation, comprises the following steps:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent, lubricant are sieved respectively, mix homogeneously obtains mixed powder then;
B. with the mixed powder direct compression, obtain label;
C. will delay in the alcoholic solution that release controlling coating material is dissolved in water or 55%～95% concentration, make concentration and be 8%～35% coating solution, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution;
D. with label with above-mentioned hybrid packet clothing liquid coating;
E. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
6, a kind of preparation method of venlafaxine hydrochloride sustained-release tablet preparation according to claim 1 is characterized in that this method adopts the preparation of dry granulation method, comprises the following steps:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent are sieved respectively, mix homogeneously obtains mixed powder then;
B. mixed powder is adopted and pulverize double compression or directly use dry granulation machine dry granulation, and add lubricant, mix homogeneously obtains granule;
C. with the granule tabletting, obtain label;
D. will delay in the alcoholic solution that release controlling coating material is dissolved in water or 55%～95% concentration, make concentration and be 8%～35% coating solution, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution;
E. with label with above-mentioned hybrid packet clothing liquid coating;
F. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
7, a kind of preparation method of venlafaxine hydrochloride sustained-release tablet preparation according to claim 1 is characterized in that this method adopts the wet granulation process preparation, comprises the following steps:
A. the gentle controlled release matrix material of VENLAFAXINE HCL, diluent are sieved respectively, mix homogeneously obtains mixed powder then;
B. use oscillating granulator to carry out wet granulation with 10% polyethylene pyrrole Lip river alkane ketone 95% alcoholic solution mixed powder: with wet granular and 50-60 ℃ of oven dry after 3-4 hour, the adding lubricant, mix homogeneously obtains granule;
C. with the granule tabletting, obtain label;
D. will delay in the alcoholic solution that release controlling coating material is dissolved in water or 55%～95% concentration, make concentration and be 8%～35% coating solution, and Pulvis Talci will be joined in the above-mentioned coating solution, and not stop to stir, must mix coating solution;
E. with label with above-mentioned hybrid packet clothing liquid coating;
F. the 40 ℃ of insulations of finished product placement that will wrap clothing got final product in 24 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100377572A CN101584674A (en) | 2008-05-21 | 2008-05-21 | Venlafaxine hydrochloride sustained-release tablet preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100377572A CN101584674A (en) | 2008-05-21 | 2008-05-21 | Venlafaxine hydrochloride sustained-release tablet preparation and preparation method thereof |
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| CN101584674A true CN101584674A (en) | 2009-11-25 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953822A (en) * | 2010-07-30 | 2011-01-26 | 合肥立方制药有限公司 | Venlafaxine hydrochloride controlled release tablets and preparation method thereof |
| CN102772390A (en) * | 2012-08-16 | 2012-11-14 | 河南新帅克制药股份有限公司 | Venlafaxine hydrochloride sustained release capsule and preparation method thereof |
| CN104622830A (en) * | 2015-03-04 | 2015-05-20 | 潍坊高新生物园发展有限公司 | Venlafaxine hydrochloride multi-layered framework controlled release tablet preparation and preparation method thereof |
| CN105982875A (en) * | 2014-12-27 | 2016-10-05 | 辽宁药联制药有限公司 | Venlafaxine sustained release preparation using waxy material as skeleton and having sustained release effect and preparation method thereof |
-
2008
- 2008-05-21 CN CNA2008100377572A patent/CN101584674A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953822A (en) * | 2010-07-30 | 2011-01-26 | 合肥立方制药有限公司 | Venlafaxine hydrochloride controlled release tablets and preparation method thereof |
| CN101953822B (en) * | 2010-07-30 | 2012-05-30 | 合肥立方制药股份有限公司 | Venlafaxine hydrochloride controlled release tablets and preparation method thereof |
| CN102772390A (en) * | 2012-08-16 | 2012-11-14 | 河南新帅克制药股份有限公司 | Venlafaxine hydrochloride sustained release capsule and preparation method thereof |
| CN102772390B (en) * | 2012-08-16 | 2014-01-08 | 乐普药业股份有限公司 | Venlafaxine hydrochloride sustained release capsule and preparation method thereof |
| CN105982875A (en) * | 2014-12-27 | 2016-10-05 | 辽宁药联制药有限公司 | Venlafaxine sustained release preparation using waxy material as skeleton and having sustained release effect and preparation method thereof |
| CN104622830A (en) * | 2015-03-04 | 2015-05-20 | 潍坊高新生物园发展有限公司 | Venlafaxine hydrochloride multi-layered framework controlled release tablet preparation and preparation method thereof |
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Open date: 20091125 |