CN103976963A - Oral solid preparation containing hydroxy propyl cellulose - Google Patents
Oral solid preparation containing hydroxy propyl cellulose Download PDFInfo
- Publication number
- CN103976963A CN103976963A CN201410185189.6A CN201410185189A CN103976963A CN 103976963 A CN103976963 A CN 103976963A CN 201410185189 A CN201410185189 A CN 201410185189A CN 103976963 A CN103976963 A CN 103976963A
- Authority
- CN
- China
- Prior art keywords
- hydroxypropyl cellulose
- oral solid
- dissolution
- clopidogrel
- solid 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 an oral solid preparation for raising dissolution rate of clopidogrel in water and a pH4.5 phosphate buffer by the use of hydroxy propyl cellulose. The solid preparation contains, by weight, 100 parts of clopidogrel bisulfate and 1-50 parts of hydroxy propyl cellulose with viscosity of 2-4000cp.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of method that improves bisulfate clopidogrel dissolution.
Technical background
Bisulfate clopidogrel is a kind of Thienopyridines, its chemical constitution and ticlopidine are similar, the optionally activation of the glycoprotein GPIIIb/IIIa complex of inhibitor adenosine diphosphate (ADP) and the combination of its platelet receptor and the ADP of secondary mediation, there is the effect of irreversible anticoagulant, be used as clinically antithrombotic reagent.The Clinical Dosage Form of bisulfate clopidogrel is mainly commodity " Plavix " by name and the oral tablet (specification is 75mg clopidogrel) of " handsome gram " and the oral tablet (specification is 25mg clopidogrel) of commodity " Tai Jia " by name at present.What wherein, Plavix tablet was used is bisulfate clopidogrel II crystal formation.Research discovery, the dissolubility of I crystal formation in water and in pH4.5 phosphate buffer is all much smaller than II crystal formation, and this may cause that the bioavailability of I crystal formation is less than II crystal formation.Yet the time that II crystal formation powder production needs, than the many 2-3 of I crystal formation doubly therefore, if can solve the low problem of I crystal formation dissolution, I crystal formation was very valuable clinical crystal formation.
Lot of experiments finds, uses tablet prepared by I crystal formation stripping curve and the Plavix all similar in the phosphate buffer of simulated gastric fluid and pH6.8, but dissolution in water and in pH4.5 phosphate buffer is all significantly lower than Plavix.Employing adds method that conventional disintegrating agent (comprising carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone etc.) improves disintegration rate to improving its dissolution without obvious effect.
Summary of the invention
The object of this invention is to provide a kind of pharmaceutical composition, it usings hydroxypropyl cellulose as solubilizing agent, can improve the dissolution of bisulfate clopidogrel I crystal formation in water and in pH4.5 phosphate buffer, solve the low problem of Dissolution of Tablet, thereby make its more effective performance therapeutical effect.
The hydroxypropyl cellulose of the bisulfate clopidogrel that the present composition contains 100 weight portions (I crystal formation) and 1-50 weight portion, preferably hydroxy propyl cellulose cellulose content is 1-20 weight portion.
In the present invention, hydroxypropyl cellulose can be commercially available all conventional hydroxypropyl cellulose.Hydroxypropyl cellulose viscosity is 2-4000cP.Preferred viscosities is the hydroxypropyl cellulose of 2-60cP.
In the present invention, when term " viscosity of hydroxypropyl cellulose " refers to 20 degrees Celsius, 2 grams of hydroxypropyl celluloses are dissolved in the viscosity of gained solution in 100 ml distilled waters.
In the present invention, the hydroxypropyl cellulose of different viscosities, model may be used alone, can also be used in combination, to the not restriction of its mixed proportion.
In compositions of the present invention, also can comprise other pharmaceutically acceptable additives.Specifically select one or more of white pharmaceutically acceptable filler, pharmaceutically acceptable binding agent and pharmaceutically acceptable lubricant.In a preferred embodiment of the present invention, the content of described additive is 50-800 weight portion.
In the present invention, described filler is one or more the compositions in mannitol, lactose, maltodextrin, sucrose, preferably lactose.Consumption for filler does not have any restriction, and it can be the conventional amount used in this area.In embodiments of the present invention, the consumption of described filler is 50-800 weight portion.
In the present invention, described lubricant is one or more the compositions in silicon dioxide, Pulvis Talci, liquid paraffin,light, Glyceryl Behenate, the compositions of preferably talc powder, liquid paraffin,light.The weight ratio of Pulvis Talci, liquid paraffin,light is 40: 1-5: 1, and preferably 20: 1.In embodiments of the present invention, described lubricant total amount is 5-50 weight portion, is preferably 10-30 weight portion.
Specific implementation method
Below in conjunction with embodiment, illustrate the present invention, the embodiment in the present invention is only for technical scheme of the present invention is described, and non-limiting essence of the present invention.Every do not deviate from the change of the present invention design or be equal to substitute all within protection scope of the present invention.
Dissolution of Tablet assay method: get this product, according to dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2010), test, water and pH4.5 phosphate buffered solution 1000ml are dissolution medium respectively, rotating speed is per minute 50 to turn, operation in accordance with the law, when 5min, 10min, 15min, 20min, 30min, 45min, getting respectively solution filters in right amount, precision measures subsequent filtrate 3.0ml, put in 10ml measuring bottle, add stripping medium to scale, shake up (complete stripping aimed concn: 22.5 μ g clopidogrel/ml); Separately get bisulfate clopidogrel reference substance appropriate, accurately weighed, add pH2.0HCl solution and dissolve and dilute the solution of making in every 1ml approximately containing clopidogrel 25 μ g.Get above-mentioned two kinds of solution, according to spectrophotography (two appendix IV A of Chinese Pharmacopoeia version in 2010), at the wavelength place of 240nm, measure respectively trap, by the absorbance ratio of the two, calculate the stripping quantity of every.
Capsule dissolution determination method: get this product, according to dissolution method (two appendix XC first methods of Chinese Pharmacopoeia version in 2010), test, water and pH4.5 phosphate buffered solution 1000ml are dissolution medium respectively, rotating speed is per minute 100 to turn, operation in accordance with the law, when 5min, 10min, 15min, 20min, 30min, 45min, getting respectively solution filters in right amount, precision measures subsequent filtrate 3.0ml, put in 10ml measuring bottle, add stripping medium to scale, shake up (complete stripping aimed concn: 22.5 μ g clopidogrel/ml); Separately get bisulfate clopidogrel reference substance appropriate, accurately weighed, add pH2.0HCI solution and dissolve and dilute the solution of making in every 1ml approximately containing clopidogrel 25 μ g.Get above-mentioned two kinds of solution, according to spectrophotography (two appendix IV A of Chinese Pharmacopoeia version in 2010), at the wavelength place of 240nm, measure respectively trap, by the absorbance ratio of the two, calculate the stripping quantity of every.
In embodiment, hydroxypropyl cellulose used is specifically purchased from Tso Tat Co., Ltd., Japan, and the hydroxypropyl cellulose of various models has following feature:
HPC-SSL: propoxyl content 53.4-77.5%, 2% solution viscosity is 2-2.9cP, 50 microns to 200 microns of particle diameters.
HPC-SL: propoxyl content 53.4-77.5%, 2% solution viscosity is 3-5.9cP, 50 microns to 200 microns of particle diameters.
HPC-L: propoxyl content 53.4-77.5%, 2% solution viscosity is 6-10cP, 50 microns to 200 microns of particle diameters.
HPC-LM: propoxyl content 53.4-77.5%, 2% solution viscosity is 20-60cP, 50 microns to 200 microns of particle diameters.
HPC-M: propoxyl content 53.4-77.5%, 2% solution viscosity is 150-400cP, 50 microns to 200 microns of particle diameters.
HPC-H: propoxyl content 53.4-77.5%, 2% solution viscosity is 1000-4000cP, 50 microns to 200 microns of particle diameters.
Embodiment 1
Preparation method: by bisulfate clopidogrel, lactose and HPC-SSL mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 2
Preparation method: by bisulfate clopidogrel, lactose and HPC-SL mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 3
Preparation method: by bisulfate clopidogrel, lactose and HPC-L mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 4
Preparation method: by bisulfate clopidogrel, lactose and HPC-LM mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 5
Preparation method: by bisulfate clopidogrel, lactose and HPC-M mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 6
Preparation method: by bisulfate clopidogrel, lactose and HPC-H mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is pressed into tablet.
Embodiment 7
Preparation method: by bisulfate clopidogrel, lactose, HPC-H, HPC-SSL mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granules, and 30 order granulate add the mixture of Pulvis Talci and liquid paraffin,light, after mix homogeneously, be pressed into tablet.
Embodiment 8
Preparation method: by bisulfate clopidogrel, lactose and HPC-SSL mix homogeneously, add appropriate 40% ethanol water, make suitable soft material, cross 30 mesh sieves, 45 degree are dried granule, 30 order granulate, the mixture that adds Pulvis Talci and liquid paraffin,light, after mix homogeneously, is filled into capsule.
Comparative example
By the method identical with embodiment 7, prepare comparative example 1, difference is only to have lacked hydroxypropyl cellulose in prescription, writes out a prescription as follows:
Comparative example 1
The commercially available Plavix sheet of comparative example 2 (
hangzhou Sai Nuofei pharmaceutical Co. Ltd produces)
Measure embodiment 1-8 and comparative example 1-2 dissolution when 5min, 10min, 15min, 20min, 30min, 45min in water and in pH4.5 phosphate buffer, result is as follows:
Table 1 embodiment 1-8 and the comparative example 1-2 dissolution (%) in water
Table 2 embodiment 1-8 and the comparative example 1-2 dissolution (%) in pH4.5 phosphate buffer
By comparative example 1 and comparative example 2 (commercially available Plavix), we are known, and the dissolution of bisulfate clopidogrel I crystal formation in water and in pH4.5 phosphate buffer is all much smaller than II crystal formation.Adding of hydroxypropyl cellulose, can improve the dissolution of bisulfate clopidogrel in water and in pH4.5 phosphate buffer, dissolution during 45min can significantly improve the level to Plavix.The dissolution of each embodiment and commercially available Plavix approaches.
Claims (5)
1. an oral solid formulation that contains hydroxypropyl cellulose, is characterized in that, it comprises the bisulfate clopidogrel of 100 weight portions and the hydroxypropyl cellulose that 1-50 weight portion viscosity is 2-4000cP.
2. the oral solid formulation that contains hydroxypropyl cellulose according to claim 1, is characterized in that, wherein the content of hydroxypropyl cellulose is 1-20 weight portion.
3. the oral solid formulation that contains hydroxypropyl cellulose according to claim 1, is characterized in that, wherein the viscosity of hydroxypropyl cellulose is 2-60cP.
4. the oral solid formulation that contains hydroxypropyl cellulose as claimed in claim 1, is characterized in that, also comprises lactose, Pulvis Talci and the liquid paraffin of 50-800 weight portion.
5. the oral solid formulation that contains hydroxypropyl cellulose as claimed in claim 1, is characterized in that, is Tablet and Capsula agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410185189.6A CN103976963A (en) | 2014-05-05 | 2014-05-05 | Oral solid preparation containing hydroxy propyl cellulose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410185189.6A CN103976963A (en) | 2014-05-05 | 2014-05-05 | Oral solid preparation containing hydroxy propyl cellulose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103976963A true CN103976963A (en) | 2014-08-13 |
Family
ID=51269294
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410185189.6A Pending CN103976963A (en) | 2014-05-05 | 2014-05-05 | Oral solid preparation containing hydroxy propyl cellulose |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103976963A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766573A (en) * | 2010-02-05 | 2010-07-07 | 上海安必生制药技术有限公司 | Preparation process of clopidogrel bisulfate solid preparation |
| CN101791309A (en) * | 2010-03-31 | 2010-08-04 | 中国药科大学 | Oral solid preparation containing clopidogrel hydrogen sulfate |
-
2014
- 2014-05-05 CN CN201410185189.6A patent/CN103976963A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766573A (en) * | 2010-02-05 | 2010-07-07 | 上海安必生制药技术有限公司 | Preparation process of clopidogrel bisulfate solid preparation |
| CN101791309A (en) * | 2010-03-31 | 2010-08-04 | 中国药科大学 | Oral solid preparation containing clopidogrel hydrogen sulfate |
Non-Patent Citations (1)
| Title |
|---|
| 漂在北方: "NISSO HPC 羟丙基纤维素", 《豆丁网 HTTP://WWW.DOCIN.COM/P-195293215.HTML》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ramasamy et al. | Formulation and evaluation of xanthan gum based aceclofenac tablets for colon targeted drug delivery | |
| Kharia et al. | Design and optimization of floating drug delivery system of acyclovir | |
| Malakar et al. | Theophylline release behavior from hard gelatin capsules containing hydrophilic polymeric matrices. | |
| Rai et al. | Superior disintegrating properties of calcium cross-linked Cassia fistula gum derivatives for fast dissolving tablets | |
| Ghosal et al. | Alginate/hydrophobic HPMC (60M) particulate systems: new matrix for site-specific and controlled drug delivery | |
| Bhattacharya et al. | Tranexamic acid loaded gellan gum-based polymeric microbeads for controlled release: In vitro and in vivo assessment | |
| Ramasamy et al. | Formulation and evaluation of chondroitin sulphate tablets of aceclofenac for colon targeted drug delivery | |
| Sokar et al. | Pulsatile core-in-cup valsartan tablet formulations: in vitro evaluation | |
| Momin et al. | Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride | |
| Svirskis et al. | Development of mucoadhesive floating hollow beads of acyclovir with gastroretentive properties | |
| Pongjanyakul et al. | Modulating drug release and matrix erosion of alginate matrix capsules by microenvironmental interaction with calcium ion | |
| CN104758941A (en) | Oral tablet capable of achieving rapid dissolution by using hydroxy propyl cellulose as adhesion agent | |
| Salih et al. | Effect of natural and synthetic polymers on the properties of candesartan cilexetil matrix tablet prepared by dry granulation | |
| RS et al. | Formulation and evaluation of gastroretentive floating tablet using Hibiscus rosa-sinensis mucilage | |
| CN103976963A (en) | Oral solid preparation containing hydroxy propyl cellulose | |
| Shah et al. | Formulation and in vitro evaluation of ofloxacin-ethocel controlled release matrix tablets prepared by wet granulation method: Influence of co-excipients on drug release rates | |
| Malviya et al. | Formulation, evaluation and comparison of sustained release matrix tablets of diclofenac sodium using tamarind gum as release modifier | |
| Shah et al. | A preliminary investigation of Moringa oleifera Lam gum as a pharmaceutical excipient | |
| JPH03240729A (en) | Solid pharmaceutical with promoted absorption for internal use | |
| Kulkarni et al. | Effect of tamarind seed polysaccharide on dissolution behaviour of ibuprofen tablets | |
| Ramya et al. | Preparation, characterization and evaluation of a new coprocessed excipient as directly compressible vehicle in tablet formulation | |
| Malviya | Swelling and erosion based formulations for the treatment of chronic seizures using (3) 2 factorial design | |
| Mohan et al. | An review on natural polymers approaches to floating drug delivery system | |
| Shetty et al. | Design and evaluation of sustained release matrix tablets of etodolac | |
| CN103142533A (en) | Enteric coated tablet of etoposide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140813 |