CN103142522B - Etoposide tablet - Google Patents
Etoposide tablet Download PDFInfo
- Publication number
- CN103142522B CN103142522B CN201310092429.3A CN201310092429A CN103142522B CN 103142522 B CN103142522 B CN 103142522B CN 201310092429 A CN201310092429 A CN 201310092429A CN 103142522 B CN103142522 B CN 103142522B
- Authority
- CN
- China
- Prior art keywords
- etoposide
- tablet
- clathrate
- comparative example
- cyclodextrin
- 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.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to an etoposide inclusion compound tablet. The etoposide is prepared into an inclusion compound, and then the inclusion compound is prepared into the tablet.
Description
Technical field
The application relates to a kind of tablet, particularly, is etoposide clathrate tablet.
Background technology
Etoposide (etoposide) is the carbohydrate metabolism product of podophyllotoxin (podophyllotoxin), belongs to cell cycle specific antitumor drug, is mainly used in treating small cell lung cancer, lymphatic cancer etc.But the absolute bioavailability of etoposide oral formulations only has 25%～75%.The poorly water-soluble of etoposide and to be decomposed into non-activity product in acid medium be the main cause that causes its oral formulations bioavailability low.
Etoposide mainly contains the dosage forms such as tablet, capsule, injection at present for clinical, and these dosage forms are poor at gastrointestinal tract dissolution, and bioavailability is not high.CN101259100A discloses a kind of etoposide preparations, wherein etoposide is prepared into phosphatide complexes, is then being prepared into the multiple dosage forms such as tablet, capsule.But this preparation cost is high, bioavailability is low, can not be advantageously applied to clinical.
Summary of the invention
The present invention, in order to solve the low shortcoming of existing etoposide preparations bioavailability, has invented etoposide clathrate tablet.
Clathrate has the following advantages: cover bad stink, reduce zest; Increase drug dissolution and bioavailability; Improve medicine stability.
Applicant finds, now etoposide is prepared into clathrate, then is prepared into tablet in conjunction with specific adjuvant, has advantages of that stability is high, disintegration rate is fast and bioavailability is high.
The application provides a kind of tablet of etoposide, comprising:
Etoposide clathrate comprises active component and enclose material, and active component is etoposide, and enclose material is hydroxypropylβ-cyclodextrin.The part by weight of active component and enclose material is 3:1-1:3, preferably 1:2.Experiment showed, alpha-cyclodextrin, beta-schardinger dextrin-, the clathrate that the etoposide clathrate that hydroxyl beta-schardinger dextrin-prepares prepares inferior to hydroxypropylβ-cyclodextrin in aspect effects such as disintegration rate, stability, dissolutions far away.
The impact of different enclose materials on etoposide clathrate
| Enclose material | Dissolution velocity (min) | Stability | Inclusion rate |
| Alpha-cyclodextrin | 12 | Generally | 80% |
| Beta-schardinger dextrin- | 14 | Generally | 82% |
| Hydroxyl beta-schardinger dextrin- | 12 | Generally | 78% |
| Hydroxypropylβ-cyclodextrin | 5 | Good | 93% |
Test method is with reference to the method for two regulations of 2010 editions Chinese Pharmacopoeias.
In this application, select specific adjuvant to prepare etoposide clathrate tablet.Wherein said filler is the compositions of lactose and microcrystalline Cellulose, the two part by weight is 7:2.3, binding agent is selected from methylcellulose or polyvidone, disintegrating agent is the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the two part by weight is 3:4.5, and lubricant is selected from micropowder silica gel or Pulvis Talci.Experimental results show that, be not that the conventional adjuvant of any pharmacy is all applicable to preparing etoposide clathrate tablet, select the etoposide clathrate tablet that this specific adjuvant prepares to be better than in the effect of the aspects such as disintegration rate, stability, dissolution the etoposide clathrate tablet that other adjuvants prepare far away.
The preparation method of etoposide clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, etoposide is reacted with hydroxypropylβ-cyclodextrin, gained solution, through extremely clarification of filtering with microporous membrane, is isolated to clathrate from mixture; Or
(2), with solid form, etoposide is reacted with hydroxypropylβ-cyclodextrin; Or
(3) etoposide reacts with hydroxypropylβ-cyclodextrin and carries out high energy milling.
Metering of the present invention is weight.
Preferably, the prescription of tablet is (by weight):
Embodiment 1 writes out a prescription
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method:
1. prepare by the following method etoposide clathrate:
(1) in water or aquiferous ethanol medium, by a certain percentage, etoposide is reacted with hydroxypropylβ-cyclodextrin, gained solution, through extremely clarification of filtering with microporous membrane, is isolated to clathrate from mixture; Or
(2), with solid form, etoposide is reacted with hydroxypropylβ-cyclodextrin; Or
(3) etoposide reacts with hydroxypropylβ-cyclodextrin and carries out high energy milling.
2. etoposide clathrate was pulverized to 100 mesh sieves, all the other adjuvants were pulverized to 80 mesh sieves; Accurately take the supplementary material of recipe quantity, mix homogeneously (except micropowder silica gel), the alcoholic solution of 3% polyvinylpyrrolidone 95% is granulated, 18 mesh sieve granulate, 40 ℃ are dry.Add the micropowder silica gel of recipe quantity, mix homogeneously, crosses 18 mesh sieves, measures granule drug content, determines sheet weight, and tabletting, obtains.Gained tablet is limited to 48 seconds while disperseing.Embodiment 2 writes out a prescription
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 49 seconds while disperseing.
Embodiment 3
Etoposide described in embodiment 1 and hydroxypropylβ-cyclodextrin are fully ground to and form even mastic in 50% ethanol, after vacuum drying white powder, in the water of this powder solubility property more not the etoposide of enclose improved 12 times.
Comparative example 1
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 142 seconds while disperseing.
Comparative example 2
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 152 seconds while disperseing.
Comparative example 3
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 169 seconds while disperseing.
Comparative example 4
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 192 seconds while disperseing.
Comparative example 5
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 135 seconds while disperseing.
Comparative example 6
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 210 seconds while disperseing.
Etoposide tablet dispersing uniformity and Their Dissolution Test in vitro
(1) according to the method for two regulations of 2010 editions Chinese Pharmacopoeias, get each 6 of embodiment 1,2 and comparative example 1-6 tablet, put in 250ml beaker, add the water 100ml of approximately 20 ℃, jolting.All disintegrate is also by No. two sieves in 2 minutes for embodiment 1,2 tablets, and the 3 minute time limit stipulating than pharmacopeia shortens 100%.The jolting of comparative example 1-6 tablet is all disintegrates by No. two sieves after 7 minutes.
(2) Dissolution Rate Testing result shows: according to dissolution method (2010 editions two appendix XC the second methods of Chinese Pharmacopoeia), using 0.01mol/L hydrochloric acid solution 900ml as dissolution medium, rotating speed is 50 revs/min, operation in accordance with the law, according to ultraviolet visible spectrophotometry, measure every stripping quantity, result be the stripping percentage rate of embodiment 1,2 tablets in 50 seconds in about 80-90%, substantially whole strippings in 90 seconds.Comparative example 1-6 sheet stripping percentage rate after 3 minutes is in 20% left and right, substantially whole in 7 minutes
Stripping.The results are shown in following table 1. and table 2.
Table 1 disperses the time limit
| Sample | Disperse the time limit (second) |
| Embodiment 1 | 48 |
| Embodiment 2 | 49 |
| Comparative example 1 | 142 |
| Comparative example 2 | 152 |
| Comparative example 3 | 169 |
| Comparative example 4 | 192 |
| Comparative example 5 | 135 |
| Comparative example 6 | 210 |
Table 2 stripping percentage rate
Experimental data by table 1 and table 2 can find out, adopted dispersibility and the dissolution optimum of the etoposide tablet (embodiment 1 and embodiment 2) that specific adjuvant prepares.
The filler type of selecting in comparative example 1 does not change, but in the compositions of lactose and microcrystalline Cellulose, the part by weight of the two changes, the disintegrating agent type of selecting in comparative example 2 does not change, but in the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the part by weight of the two changes, in comparative example 3, filler changes to starch, comparative example's 4 binding agents and lubricant change to sodium alginate and magnesium stearate, in comparative example 5, disintegrating agent changes to cross-linking sodium carboxymethyl cellulose, in comparative example 6, filler changes to lactose, binding agent changes to hypromellose, disintegrating agent changes to carboxymethyl starch sodium, lubricant changes to calcium stearate.Experimental data by table 1 and table 2 can be found out, in the identical situation of each composition consumption, no matter be that change has occurred adjuvant type, or adjuvant type does not change but changed the usage ratio of component, the dispersibility of the etoposide tablet preparing and dissolution all significantly reduce.
The test of etoposide tablet stability
Outward appearance, dissolution, content and the disintegration time of the tablet to embodiment 1,2 and comparative example 1-6 have been carried out factors influencing.
(1) hot test: get embodiment 1,2 and comparative example 1-6 sample is laid in culture dish in right amount, the calorstat that is placed in 60 ℃ is placed 10 days, during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
(2) high wet test: sample thief is laid in culture dish is in right amount placed 10 days under the condition of 25 ℃ of relative humidity RH90% ± 5%, and during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
(3) strong illumination test, sample thief is laid in culture dish in right amount, is placed in light cupboard the condition illumination of 4500Lx ± 500Lx 10 days, and during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
Hot and humid and the high light stability inferior of the each embodiment tablet of table 3.
Experimental data by table 3 can be found out, no matter be that change has occurred adjuvant type, or adjuvant type does not change but has changed the usage ratio of component, and the stability of the etoposide tablet preparing (comparative example 1-6) all significantly reduces with respect to embodiment 1,2.
Claims (1)
1. an etoposide tablet, is characterized in that: prescription is by weight:
Wherein etoposide in etoposide clathrate: hydroxypropylβ-cyclodextrin weight ratio is 1:2, in the compositions of lactose and microcrystalline Cellulose, the two part by weight is 7:2.3, in the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the two part by weight is 3:4.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310092429.3A CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310092429.3A CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103142522A CN103142522A (en) | 2013-06-12 |
| CN103142522B true CN103142522B (en) | 2014-04-30 |
Family
ID=48541038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310092429.3A Active CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103142522B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110170058B (en) * | 2019-06-24 | 2022-02-11 | 李建恒 | Abiraterone clathrate compound and preparation method thereof |
-
2013
- 2013-03-21 CN CN201310092429.3A patent/CN103142522B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 孙鹤文等.中等取代度的羟丙基－β－环糊精对依托泊苷的包埋特性分析.《药物分析杂志》.2011,第31卷(第11期),第2103页右栏第3行至第5行，第2104页第2.4栏和第3.1栏. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103142522A (en) | 2013-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103083278B (en) | Roxithromycin capsule and preparation method thereof | |
| CN102764264A (en) | Celecoxib solid composition with high dissolution, preparation method and application | |
| CN103610658B (en) | Immunomodulator slow-release preparation and preparation method thereof | |
| CN107320456A (en) | 2-acetylamino-2-deoxy-D-glucose capsule preparations and preparation method thereof | |
| CN102302466A (en) | Capecitabine medicinal composition capable of direct powder tableting, and application thereof | |
| CN102846570B (en) | Cefditoren pivoxil composition tablets and preparation method thereof | |
| CN103142533B (en) | Enteric coated tablet of etoposide | |
| CN103142522B (en) | Etoposide tablet | |
| CN102274162A (en) | Solid composition comprising insoluble medicine and hydrophilic gel material and preparation method thereof | |
| CN103142500B (en) | Sustained-release particle of etoposide | |
| CN103142530B (en) | Sustained-release tablet of etoposide | |
| CN103142545B (en) | Enteric capsule of etoposide | |
| CN103142499B (en) | Etoposide particle | |
| CN105030707A (en) | Method for preparing clotrimazole buccal tablets on basis of all-powder direct pressing of modified glucose | |
| CN103393616B (en) | Tamoxifen citrate tablets | |
| CN103142497B (en) | Enteric granule of etoposide | |
| CN103393604A (en) | Tamoxifen citrate enteric coated particles | |
| CN102846579B (en) | Valsartan medicinal capsule and preparation method thereof | |
| CN103405782A (en) | Inclusion compound containing celecoxib and preparation method thereof | |
| CN103284972B (en) | Prescription of clopidogrel bisulfate tablet and preparation process thereof | |
| CN104644601A (en) | Capecitabine tablet | |
| CN103349650B (en) | Tamoxifen citrate sustained-release tablets | |
| CN103393603B (en) | Tamoxifen citrate particles | |
| CN106539776A (en) | A kind of difficult to understand card friend's pharmaceutical composition and preparation method thereof | |
| CN104257617A (en) | Itopride hydrochloride oral preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 266103 Qingdao economic and Technological Development Zone, unity Road, No. 3601, Shandong Applicant after: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. Address before: 266103 Haier Road, Shandong, Qingdao, No. 1 Applicant before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee after: Zhengda Pharmaceutical (Qingdao) Co., Ltd. Address before: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |