CN104161735A - Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof - Google Patents
Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof Download PDFInfo
- Publication number
- CN104161735A CN104161735A CN201310186202.5A CN201310186202A CN104161735A CN 104161735 A CN104161735 A CN 104161735A CN 201310186202 A CN201310186202 A CN 201310186202A CN 104161735 A CN104161735 A CN 104161735A
- Authority
- CN
- China
- Prior art keywords
- slow releasing
- preparation
- premix
- mesh sieves
- releasing preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention relates to a sustained-release preparation containing pramipexole hydrochloride and a preparation method thereof. The sustained-release preparation contains pramipexole hydrochloride, hydroxypropyl methylcellulose, starch, hydroxypropylcellulose, aerosil, magnesium stearate, etc. The release degree of sustained-release preparation release does not change with dissolution mediums and is in accordance with the release mechanism of the sustained-release preparation; and the preparation method for the preparation is simple and can easily realize industrialized production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of slow releasing preparation that contains body of Pramipexole dihydrochloride and preparation method thereof.
Technical background
Parkinson disease are nervous system degeneration diseases of a kind of common slow progress that betides middle-aged and elderly people, clinical taking static tremor, myotonia and the dyskinesia as principal character.Along with the process of population aging, its prevalence increases year by year, has become the nervous system common disease that is only second to cerebrovascular.For a long time, be the preferred option for the treatment of of Parkinson disease taking levodopa as main medicine replacement therapy. but existing treatment measure all can not effectively stop and even the Parkinsonian that appears as of the non-Ergota class dopamine-receptor stimulant pramipexole of the progress of the disease that slows down a new generation has brought hope.
The chemical name of body of Pramipexole dihydrochloride is S (-)-2-amino-6-n-propylamine base-4,5,6,7-tetrahydro benzothiazol dihydrochloride.Current commercially available pramipexole ordinary tablet needs taken three times a day, in view of parkinson patient handicapped to existing, and be difficult to the problem that ensures that rule is taken medicine, U.S. FDA has been ratified two body of Pramipexole dihydrochloride (pramipexoledihydrochloride) the slow releasing tablet MirapexElk of BoehringerIngelheim pharmaceutical Co. Ltd exploitation, and progressive stage idiopathic parkinsonian's early stage for 1 time on the one oral medication disease S&S.And that applicant finds that in research process aqueous medium stripping is put into in commercially available prod is very low, and aqueous medium is an important factor evaluating stripping, in drug preparation technique (Ling Peixue chief editor) slow release of for example publishing for 2007 and controlled release preparation chapters and sections " release medium ", explicitly point out " the fresh purified water of removing air is best slow release medium ", and a high-quality medicine, in the time adopting certain dissolving device and rotating speed, (simulated gastric fluid (pH1.0-1.2) in four kinds of media, pH4.0-4.5, simulated intestinal fluid pH6.8 and water) all should there is certain stripping curve, so just can ensure this medicine for human body time, can in various internal milieus, all there be certain stripping or release, all there is certain curative effect for the patient of any body constitution.
Chinese patent CN1671381A discloses the slow release formulation being administered once a kind of every day of pramipexole, it comprises treats the pramipexole of effective dose or its salt, the starch of 40%-70%, the hypromellose of 30%-60% and at least one pharmaceutically acceptable excipient, preparation technology adopts outsourcing extended release coatings film after the ground medicine matrix core of direct powder compression, this technique more complicated, and very high to production equipment and affected requirement.Chinese patent CN1671382A adopting process is identical with CN1671381A, has same technical problem.
Chinese patent ZL200580027635.X discloses and has comprised pramipexole or its prolongation slow releasing preparation with salt, in said preparation, comprise two kinds of polymer, a kind of is pregelatinized Starch, another kind is anionic polymer, this slow releasing preparation is in the buffer of pH4.5 and pH6.8, discharge slowly, within 24 hours, stripping release rate is only 80%, and the vitro release that pH6.8 buffer is intestinal juice environment in analogue body is measured explanation, as the main position Duodeno-small intestinal of drug absorption, as medicine can not discharge completely, bioavailability will reduce, applicant studies it and in aqueous medium, also has the very low phenomenon of stripping simultaneously, stripping in 24 hours is no more than 20%.The cost of the anionic polymers such as while carbomer is also higher.
Chinese patent CN102836137A discloses a kind of slow releasing preparation that contains body of Pramipexole dihydrochloride, hypromellose, hyprolose, microcrystalline Cellulose and magnesium stearate, and said preparation obtains by wet granulation; Chinese patent CN102406626A discloses a kind of slow releasing preparation that contains body of Pramipexole dihydrochloride, ethyl cellulose, hydroxypropyl emthylcellulose, pregelatinized Starch, silica sol and magnesium stearate.Applicant finds in research process, and the preparation of Chinese CN102836137A exists prominently releases phenomenon, and in the buffer of pH1.2, pH4.5 and pH6.8, it discharged and exceed 40% after 1 hour; The preparation of Chinese patent CN102406626A is in above-mentioned three kinds of media, and it discharged and also approach 30% after 1 hour, has the prominent phenomenon of releasing in 4-6 hour pH6.8 medium simultaneously.
Summary of the invention
In order to solve the dependence dissolution medium existing in prior art, existing dashes forward releases the problems such as phenomenon, the invention provides one not relying on dissolution medium, can reach basically identical release, and not existing dashes forward releases phenomenon, more meets the slow releasing preparation that contains pramipexole of release mechanism.
One aspect of the present invention provides a kind of slow releasing preparation that contains pramipexole hydrochlorate, contains the component of following percentage by weight in this slow releasing preparation:
Body of Pramipexole dihydrochloride 0.1-1%
Hypromellose 40-70%
Starch 5-30%
Hyprolose 5-35%
Micropowder silica gel 1-5%
Magnesium stearate 1-5%.
Preferred described starch is pregelatinized Starch, corn starch or the two mixture.
The present invention further provides a kind of slow releasing preparation that contains pramipexole hydrochlorate, in this slow releasing preparation, comprise the component of following weight percentage:
The present invention further provides a kind of slow releasing preparation that contains pramipexole hydrochlorate, and this slow releasing preparation is made up of the component of following weight percentage:
The present invention further provides a kind of slow releasing preparation that contains pramipexole hydrochlorate, and this slow releasing preparation is made up of the component of following weight percentage:
The present invention further provides a kind of slow releasing preparation that contains pramipexole hydrochlorate, and this slow releasing preparation is made up of the component of following weight percentage:
The viscosity of hypromellose described in above-mentioned preparation is 10000-100000mpa.s, preferably 15000mpa.s.Above-mentioned slow releasing preparation is preferably tablet.
The present invention also further provides a kind of preparation method of the slow releasing tablet that contains body of Pramipexole dihydrochloride, and this preparation method comprises following steps:
1) body of Pramipexole dihydrochloride is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after body of Pramipexole dihydrochloride and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder;
6) tabletting, Hardness Control 8-15kg.
In above-mentioned preparation method, hardness is preferably 11Kg/cm
2.
The present invention compared with prior art its release does not only rely on dissolution medium and more meets slow release rule, does not have the prominent phenomenon of releasing.
Pregelatinized Starch described in the present invention is the various starch (as corn starch, potato starch, wheaten starch etc. modification becomes pregelatinized Starch) by modification, and commercially available various pre-paying starch.
The viscosity grade that hydroxypropyl emthylcellulose of the present invention (HPMC) has is preferably about 5000mpa.s to about 100000mpa.s, is preferably 10000mpa.s to about 100000mpa.s, and most preferably 10000mpa.s is to 30000mpa.s.
Hydroxypropyl cellulose of the present invention can low-substituted hydroxypropyl cellulose can be also Hydroxypropylcelliloxe, and having viscosity is that about 150mpa.s is to about 10000mpa.s, preferably from 4000 to 6500mpa.s.
The present invention relates to account form and the evaluation index of similar factors f2: f2 value is to be calculated by following formula, if the f2 value that the dissolution rate of each preparation calculates, in 50≤f2≤100, has similar dissolution characteristic between preparation.The present invention adopt altogether 1,2,4,6,8,12,16,20,24 hour the dissolution rate of totally 9 time points in order to calculate f2 value.
Wherein Ti and Ri are the stripping percentage ratio at each time point; N is the number that will compare.
Brief description of the drawings
Fig. 1 is commercially available slow releasing tablet release profiles in four kinds of different mediums
Fig. 2 is the application's slow releasing tablet (embodiment mono-) release profiles in four kinds of different mediums
Fig. 3 is four kinds of different slow releasing tablet (embodiment bis-) release profiles in the medium of pH1.2
Fig. 4 is four kinds of different slow releasing tablet (embodiment bis-) release profiles in the medium of pH4.5
Fig. 5 is four kinds of different slow releasing tablet (embodiment bis-) release profiles in the medium of pH6.8
Fig. 6 is four kinds of different slow releasing tablet (embodiment bis-) release profiles in pure water medium
Fig. 7 is the application's slow releasing tablet (embodiment tetra-) release profiles in four kinds of different mediums
Fig. 8 is the application's slow releasing tablet (embodiment five) release profiles in four kinds of different mediums
Fig. 9 is the application's slow releasing tablet (embodiment six) release profiles in four kinds of different mediums
Figure 10 is the application's slow releasing tablet (embodiment seven) release profiles in four kinds of different mediums
Figure 11 is the application's slow releasing tablet (embodiment eight) release profiles in four kinds of different mediums
Figure 12 is the application's slow releasing tablet (embodiment nine) release profiles in four kinds of different mediums
Figure 13 is the application's slow releasing tablet (embodiment ten) release profiles in four kinds of different mediums
Figure 14 is the application's slow releasing tablet (embodiment 11) release profiles in four kinds of different mediums
Figure 15 is the application's slow releasing tablet (embodiment 12) release profiles in four kinds of different mediums
Figure 16 is the application's slow releasing tablet (embodiment 13) release profiles in four kinds of different mediums
Figure 17 is the application's slow releasing tablet (embodiment 14) release profiles in four kinds of different mediums
Figure 18 is the application's slow releasing tablet (embodiment 15) release profiles in four kinds of different mediums
Figure 19 is the application's slow releasing tablet (embodiment 16) release profiles in four kinds of different mediums
Detailed description of the invention
1, the collocation method of dissolution medium:
PH6.8 buffer: 250ml0.2mol/l potassium dihydrogen phosphate and 0.2mol/l sodium hydroxide 118ml are added in 1000ml measuring bottle, be diluted with water to 1000ml, adjust pH to 6.8 and get final product.
PH4.5 buffer: 250ml0.2mol/l potassium dihydrogen phosphate is added in 1000ml measuring bottle, be diluted with water to 1000ml, adjust pH to 4.5 and get final product.
PH1.2 buffer: precision measures 7.65ml hydrochloric acid to 1000ml measuring bottle, is diluted with water to scale, shakes up, adjusts pH to 1.2 and get final product.
Water: institute's water is self-control ultra-pure water (excellent general ultra-pure water instrument: UPT-1-100L).The about 18.25M Ω of its electric conductance * cm, pH=6.6142, dissolution method: turn/min of basket method 100, temperature 37.5, sampling time point 1,2,4,6,8,12,16,20,24 hours
Detection method:
Mobile phase methanol-ammonium formate buffer (pH=5.0)=15:85
Flow velocity 1.0ml/min
Detect wavelength 262nm
Chromatographic column: C18(Waters symmety C185 μ m4.6*150mm)
The stripping of the commercially available pramipexole slow releasing tablet of embodiment mono-and the application's slow releasing tablet is measured
Commercially available pramipexole slow releasing tablet: German Boehringer Ingelheim Boehringer Ingelheim Pharma GmbH & Co.KG (manufacturer), trade name Mirapex ER, lot number 203418D, specification: 30 slices/bottle of 0.375mg/ sheets.
The application's pramipexole slow releasing tablet:
1. preparation composition:
Table 1 the application slow releasing preparation composition
Preparation technology:
1) raw material is crossed 120 mesh sieves, hypromellose (K15M:10000-30000mpa.s; Average viscosity 15000mpa.s) cross 80 mesh sieves, all the other adjuvants are crossed 65 mesh sieves and are carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after corn starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 13kg, sheet is heavily controlled at 250mg.
The dissolution testing result of the two is shown in Fig. 1 and Fig. 2, as can be seen from Figure 1, commercially available slow releasing tablet is very poor as the dissolubility of medium at water, 26 hours are no more than 20%, and the application's slow releasing tablet dissolution in four kinds of media is basically identical, illustrate that the application's slow releasing tablet is not affected by pH value, is easier to absorption of human body.
The stripping comparison of embodiment bis-different slow releasing preparation
Commercially available slow releasing preparation: with embodiment mono-
The application's slow releasing preparation: with embodiment mono-
CN102836137A records slow releasing preparation, prepares 0.375mg/ sheet with reference to its description page 4 embodiment 2
CN102406626A records slow releasing preparation, prepares 0.375mg/ sheet with reference to its Instructions Page 3 embodiment 1
The dissolution testing result of above-mentioned preparation is in Table 1-3, Fig. 3 (pH1.2), Fig. 4 (pH4.5), Fig. 5 (pH6.8), Fig. 6 (water).
Table 2 dissolution medium is the release conditions comparison of pH1.2
| ? | Commercially available | The application | CN102836137A | CN102406626A |
| The f2 factor | Reference | 74.00 | 19 | 42 |
Table 3 dissolution medium is the release conditions comparison of pH4.5
| ? | Commercially available | The application | CN102836137A | CN102406626A |
| The f2 factor | Reference | 66.00 | 17 | 41 |
Table 4 dissolution medium is the release conditions comparison of pH6.8
| ? | Commercially available | The application | CN102836137A | CN102406626A |
| The f2 factor | Reference | 58.00 | 13 | 26 |
From table 1-3 and Fig. 3-6 result, the application's slow releasing preparation and commercially available prod are the most approaching, also absolutely prove the reliability of its curative effect, and its stripping at aqueous medium is simultaneously also very good.And the slow releasing preparation of CN102836137A prescription exists the prominent phenomenon of releasing, in its three kinds of media outside dewatering about 1 hour, stripping exceedes 40%, even up to 60%; And the slow releasing preparation of CN102406626A is write out a prescription in above-mentioned three kinds of media, it discharged and also approaches 30% after 1 hour, simultaneously in 4-6 hour pH6.8 and pH4.5 medium, had the prominent phenomenon of releasing.
Embodiment tri-
Preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after corn starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 13kg, sheet is heavily controlled at 250mg.
1, the investigation of hypromellose (K100M) consumption
The preparation composition of the different hydroxy propyl cellulose cellulose contents of table 5
Table 6 dissolution medium is the release conditions comparison of pH6.8 and pH1.2
2, the investigation of hypromellose (K15M) consumption
The preparation composition of the different hypromellose content of table 7
Table 8 dissolution medium is the release conditions comparison of pH6.8
| ? | Commercially available | 45%HPMC | 50%HPMC | 60%HPMC |
| The f2 factor | Reference | 60 | 65 | 68 |
2, the investigation of hyprolose (low replacement) consumption
The preparation composition of table 9 low-substituted hydroxypropyl cellulose (viscosity 150-400mpa.s) different content
Table 10 dissolution medium is the release conditions comparison of pH6.8
| ? | Commercially available | 5% hydroxypropyl | 10% hydroxypropyl | 20% hydroxypropyl | 30% hydroxypropyl | 35% hydroxypropyl |
| The f2 factor | Reference | 46 | 52 | 54 | 56 | 37 |
Embodiment tetra-
1, preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after pregelatinized Starch, hyprolose (H-HPC) (viscosity is 4000-6500mpa.s), micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 11kg, sheet is heavily controlled at 250mg.
2, preparation composition:
Table 11 slow releasing preparation composition
It is fine that stripping in four kinds of media the results are shown in Figure 7, four kinds of curve degrees of fitting, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment five
1, preparation technology: with reference to embodiment 4
2, preparation composition:
Table 12 slow releasing preparation composition
It is fine that stripping in four kinds of media the results are shown in Figure 8, four kinds of curve degrees of fitting, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment six
Preparation technology: with reference to embodiment tetra-
Preparation composition:
Table 13 slow releasing preparation composition
It is fine that stripping in four kinds of media the results are shown in Figure 9, four kinds of curve degrees of fitting, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment seven
Preparation technology: with reference to embodiment tetra-
Preparation composition:
Table 14 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 10, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment eight
Preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after pregelatinized Starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 11kg, sheet is heavily controlled at 330mg.
Preparation composition:
Table 15 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 11, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment nine
Preparation technology: with reference to embodiment seven
Preparation composition:
Table 16 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 12, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment ten
Preparation technology: with reference to embodiment seven
Preparation composition:
Table 17 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 13, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 11
Preparation technology: with reference to embodiment seven
Preparation composition:
Table 18 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 14, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 12
Preparation technology: with reference to embodiment seven, pregelatinized Starch is changed to composite starch.
Preparation composition
Table 19 slow releasing preparation composition
Wherein composite starch is the mixture of pregelatinized Starch and corn starch, and mixed proportion is 73:27(percentage by weight).
Stripping in four kinds of media the results are shown in Figure 15, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 13
1) preparation technology: raw material is crossed 120 mesh sieves, hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and are carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after pregelatinized Starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 13kg, sheet is heavily controlled at 500mg.
Preparation composition:
Table 20 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 16, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 14
Preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after corn starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 10kg, sheet is heavily controlled at 500mg.
Preparation composition:
Table 21 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 17, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 15
Preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after corn starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 15kg, sheet is heavily controlled at 500mg.
Preparation composition:
Table 22 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 18, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Embodiment 16
Preparation technology:
1) raw material is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after raw material and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after corn starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder.
6) tabletting, hardness 13kg, sheet is heavily controlled at 500mg.
Preparation composition:
Table 23 slow releasing preparation composition
Stripping in four kinds of media the results are shown in Figure 19, and four kinds of curve degrees of fitting are fine, illustrates that this Dissolution of Sustained Release Tablet is not affected by pH value, is easier to absorption of human body.
Claims (10)
1. contain a slow releasing preparation for body of Pramipexole dihydrochloride, it is characterized in that the component that comprises following weight percentage in described preparation:
2. slow releasing preparation according to claim 1, is characterized in that described starch is pregelatinized Starch, corn starch or the mixture of the two.
3. slow releasing preparation according to claim 2, is characterized in that the component that comprises following weight percentage in described preparation:
4. slow releasing preparation according to claim 3, is characterized in that described preparation is made up of the component of following weight percentage:
5. slow releasing preparation according to claim 3, is characterized in that described preparation is made up of the component of following weight percentage:
6. slow releasing preparation according to claim 3, is characterized in that described preparation is made up of the component of following weight percentage:
7. according to the slow releasing preparation described in any one in claim 1-6, the viscosity that it is characterized in that described hypromellose is 10000-100000mpa.s, preferably 10000-30000mpa.s; Described hydroxypropyl cellulose is the high hyprolose replacing, and viscosity is 4000-6500mpa.s.
8. according to the slow releasing preparation described in any one in claim 1-6, it is characterized in that described slow releasing preparation is tablet.
9. slow releasing preparation according to claim 8, is characterized in that the preparation method of described slow releasing tablet comprises following steps:
1) body of Pramipexole dihydrochloride is crossed 120 mesh sieves, and hypromellose is crossed 80 mesh sieves, and all the other adjuvants are crossed 65 mesh sieves and carried out pretreatment;
2) after body of Pramipexole dihydrochloride and hypromellose equivalent are progressively increased and mixed homogeneously, cross 80 mesh sieves and disperse, as premix 1;
3) by after starch, hyprolose, micropowder silica gel mix homogeneously, as premix 2;
4), by after premix 1 and 2 mix homogeneously, cross 65 mesh sieves and disperse, as premix 3;
5) premix 3 and magnesium stearate are always mixed, obtain body of Pramipexole dihydrochloride slow releasing tablet medicated powder;
6) tabletting, Hardness Control 8-15kg/cm
2.
10. slow releasing preparation according to claim 9, is characterized in that described hardness is 11kg/cm
2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310186202.5A CN104161735A (en) | 2013-05-19 | 2013-05-19 | Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310186202.5A CN104161735A (en) | 2013-05-19 | 2013-05-19 | Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104161735A true CN104161735A (en) | 2014-11-26 |
Family
ID=51905866
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310186202.5A Pending CN104161735A (en) | 2013-05-19 | 2013-05-19 | Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104161735A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104606162A (en) * | 2015-01-07 | 2015-05-13 | 海南康虹医药科技开发有限公司 | Pramipexole dihydrochloride sustained release preparation and preparation method thereof |
| CN107951853A (en) * | 2016-10-17 | 2018-04-24 | 四川海思科制药有限公司 | A kind of body of Pramipexole dihydrochloride sustained release pharmaceutical composition and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849921A (en) * | 2004-08-13 | 2010-10-06 | 贝林格尔·英格海姆国际有限公司 | The prolongation release tablet that comprises pramipexole or its officinal salt |
| CN102406626A (en) * | 2011-12-02 | 2012-04-11 | 深圳海王药业有限公司 | Pramipexole hydrochloride slow release tablet and preparation method thereof |
| CN102836137A (en) * | 2012-09-21 | 2012-12-26 | 山东齐都药业有限公司 | Pramipexole dihydrochloride slow-release tablet with high content uniformity and preparation method thereof |
-
2013
- 2013-05-19 CN CN201310186202.5A patent/CN104161735A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849921A (en) * | 2004-08-13 | 2010-10-06 | 贝林格尔·英格海姆国际有限公司 | The prolongation release tablet that comprises pramipexole or its officinal salt |
| CN102406626A (en) * | 2011-12-02 | 2012-04-11 | 深圳海王药业有限公司 | Pramipexole hydrochloride slow release tablet and preparation method thereof |
| CN102836137A (en) * | 2012-09-21 | 2012-12-26 | 山东齐都药业有限公司 | Pramipexole dihydrochloride slow-release tablet with high content uniformity and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104606162A (en) * | 2015-01-07 | 2015-05-13 | 海南康虹医药科技开发有限公司 | Pramipexole dihydrochloride sustained release preparation and preparation method thereof |
| CN104606162B (en) * | 2015-01-07 | 2017-03-29 | 海南康虹医药科技开发有限公司 | A kind of body of Pramipexole dihydrochloride slow releasing preparation and preparation method thereof |
| CN107951853A (en) * | 2016-10-17 | 2018-04-24 | 四川海思科制药有限公司 | A kind of body of Pramipexole dihydrochloride sustained release pharmaceutical composition and preparation method thereof |
| CN107951853B (en) * | 2016-10-17 | 2022-04-08 | 海思科制药(眉山)有限公司 | Pramipexole dihydrochloride sustained-release pharmaceutical composition and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Badwan et al. | Chitin and chitosan as direct compression excipients in pharmaceutical applications | |
| CN103845335B (en) | Gefitinib pharmaceutical composition and the tablet containing this gefitinib pharmaceutical composition | |
| Bhattacharya et al. | Tranexamic acid loaded gellan gum-based polymeric microbeads for controlled release: In vitro and in vivo assessment | |
| CN102836137A (en) | Pramipexole dihydrochloride slow-release tablet with high content uniformity and preparation method thereof | |
| CN103622929A (en) | Acotiamide hydrochloride sustained release tablet and preparation method thereof | |
| Alzahrani et al. | Design and optimization of ciprofloxacin hydrochloride biodegradable 3D printed ocular inserts: Full factorial design and in-vitro and ex-vivo evaluations: Part II | |
| CN104161735A (en) | Sustained-release preparation containing pramipexole hydrochloride and preparation method thereof | |
| Moin et al. | Modulation of drug release from natural polymer matrices by response surface methodology: In vitro and in vivo evaluation | |
| CN104523686A (en) | Acotiamide hydrochloride medicinal preparation and preparation method thereof | |
| CN105343028A (en) | Medicine composition with norfloxacin and method for preparing medicine composition | |
| CN103816135A (en) | Memantine hydrochloride sustained release preparation and preparing method thereof | |
| CN101084912A (en) | Compound ambroxol hydrochloride sustained-release tablet and preparation method thereof | |
| Patel et al. | Development and evaluation of controlled release ibuprofen matrix tablets by direct compression technique | |
| CN110917161A (en) | Metronidazole tablet and preparation method thereof | |
| CN103301468B (en) | The luteolin composition of high-load | |
| CN105769883A (en) | Compound sulfamethoxazole dispersible tablet and preparation method thereof | |
| CN103989643B (en) | Tablet containing ramelteon and copolyvidone | |
| CN109966256B (en) | Pramipexole sustained-release pharmaceutical composition, preparation method and application thereof | |
| Zeeshan et al. | Application of Similarity Factor (f 2) and Time Required to Drug Release (t%) Indicators for Dissolution Profiles Comparison of Paracetamol Tablets. | |
| CN106983728B (en) | Pramipexole sustained release tablet and preparation method thereof | |
| CN106932506A (en) | A kind of slow controlled-release solid formulations detection pre-treating method of hydrogel matrix type | |
| CN110693843A (en) | Lurasidone hydrochloride hydrophilic gel skeleton tablet and preparation method thereof | |
| CN103349654A (en) | Cefuroxime axetil pharmaceutical composition | |
| CN103230423B (en) | Compound prcetmol zinc gluconte tablet and preparation method thereof | |
| CN108498477A (en) | A kind of Pharmaceutical composition and preparation method thereof of 2- amino-metadiazine compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20141126 |