CN102670541A - Hydrochloride sinomenine composition and preparation method of hydrochloride sinomenine composition - Google Patents
Hydrochloride sinomenine composition and preparation method of hydrochloride sinomenine composition Download PDFInfo
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- CN102670541A CN102670541A CN2011100616679A CN201110061667A CN102670541A CN 102670541 A CN102670541 A CN 102670541A CN 2011100616679 A CN2011100616679 A CN 2011100616679A CN 201110061667 A CN201110061667 A CN 201110061667A CN 102670541 A CN102670541 A CN 102670541A
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Abstract
The invention relates to a novel formula for an osmotic pump tablet of hydrochloride sinomenine and a preparation method of the hydrochloride sinomenine composition. In a tablet core, sucrose, fructose, glucose, lactose, mannitol, sorbitol or a mixture of the sucrose, fructose, glucose, lactose, mannitol and sorbitol is selected as an osmosis accelerator, the mixture of CMCNa (sodium carboxymethylcellulose) and PVP (polyvinyl pyrrolidone) is used as an osmosis acceleration polymer, and acidic substances in right amounts are added, thereby obtaining the osmotic pump tablet of the hydrochloride sinomenine with satisfactory vitro release effect.
Description
Technical field
The present invention relates to a kind of sinomenine hydrochloride osmotic pump tablet and preparation method thereof.
Background technology
In recent years, the research and development of novel route of administration have caused that people pay attention to widely.In the preparation of on market, selling; Sustained-release preparation has been compared remarkable advantages with other preparations; Controlled releasing penetrant pump is as typical case's representative of controlled release preparation, and it is obvious to have the zero-order release characteristic, and drug release behavior does not receive the influence of factors such as media environment pH value, gastrointestinal peristalsis and food; And characteristics such as release dependency in inside and outside is good, become domestic and international new drug research exploitation focus.At present, existing multiple both at home and abroad osmotic pump preparation comes out osmotic pump tablet, oxibutynin controlled release tablet, doxazosin-mesylate controlled-releasing tablet, Nifedipine controlled-release tablet and Glipizide controlled release tablets etc. when the example hydrochloric acid verapamil is selected.
Sinomenine is the effective alkaloid monomer that from Caulis Sinomenii, extracts, and mostly medicinal is its hydrochlorate, is mainly used in the treatment rheumatoid arthritis clinically.Confirm sinomenine and international therapeutic equivalence of treating rheumatismal standard drug methotrexate through long term test, but untoward reaction is little, better tolerance.The biological half-life of sinomenine is shorter, and the ordinary tablet day of listing obeys 3-4 time at present, and slow releasing tablet day obeys 2 times.In order to reach stable blood concentration more in vivo, reduce administration number of times, improve patient's adaptability, prior art has been reported the osmotic pump type controlled release tablet of relevant sinomenine at present.
Chinese patent CN1371680A (open day on October 2nd, 2002); Coculine osmosis pump type release-controlled preparation is disclosed; Short penetrating agent wherein can be selected from low molecule saccharide, inorganic salts, and other short osmo active substances are selected from polyvinylpyrrolidone (PVP), sodium carboxymethyl cellulose (CMCNa), polyethylene glycols, tartaric acid, tween etc.The disclosed sodium chloride that all is to use of embodiment is short penetrating agent.The inventor finds in practice; The disclosed multiple short penetrating agent of this patent; Be not the osmotic pump tablet that all is applicable to the preparation sinomenine hydrochloride, when doing to urge penetrating agent with inorganic salts chemical compound such as sodium chloride, potassium chloride or magnesium chloride, the stripping of medicine very slowly; Accumulative total release rate during 24h does not meet clinical demand far below ideal release degree 90%.
" preparation of sinomenine hydrochloride oral osmotic pump controlled-releasing tablet and release factors influencing " (Shenyang Pharmaceutical University's journal; 2003; 20 (3): 165-169) literary composition discloses with the sinomenine hydrochloride oral osmotic pump controlled-releasing tablet of sodium chloride for short penetrating agent, does not contain acid ingredient in its prescription.Can see that by document Fig. 1 when the sodium chloride consumption was 35.2% and 41.5%, the 24h drug release did not meet 24h and discharges 90% requirement about 60% and 80%; Simple increase sodium chloride consumption is 54.7% o'clock; Can reach about 90% though 24h discharges; But there is flex point in this stripping curve, with the zero level equation release degree and time are carried out match and can not obtain good correlation coefficient, so the zero level that medicine is difficult to be implemented in the 24h discharges.And " common-ion effect is to the influence of propranolol hydrochloride osmotic pump tablet rate of releasing drug " (Chinese pharmacist; 2006; 9 (2): 99-101) the 100th page of Fig. 3 of a literary composition contrasted the release result of prescription A that does not add sodium chloride and the prescription B that adds sodium chloride; Though it is thus clear that the two accumulative total release degree when 12h is very nearly the same, prescription B pro-3h discharges slowly, has time lag.This also points out for for sinomenine hydrochloride that propranolol hydrochloride has identical acid group, when adding sodium chloride in the label when preparing osmotic pump tablet, also possibly have Time Delay.
" preparation of insoluble drug Atenolol Monolithic Osmotic Pump Tablet " (Chinese Pharmaceutical Journal, 2008,43 (9): 680-683), disclosing Atenolol Monolithic Osmotic Pump Tablet, is short penetrating agent with sodium chloride wherein.Atenolol is as a kind of slightly solubility material, and dissolubility is lower in water, in label, adds tartaric acid, and purpose is to make tartaric acid and atenolol molecule neutral and alkali radical reaction to improve the solvability of atenolol.And the document points out that also the method for this acid-base reaction solubilize drugs is thirsted for being generalized to other and is insoluble in water, but has the solubilising of acid-base reaction ability medicine and the preparation of osmotic pump tablet.Wherein prompting can add acidic materials and prepares osmotic pump tablet medicine soluble in water also is suitable for.And also prompting adding acidic materials can not solve Time Delay.
Summary of the invention
The invention provides a kind of new sinomenine hydrochloride osmotic pump tablet prescription and the method for preparing of osmotic pump tablet; Select for use mannitol and milk-sugar mixture as short penetrating agent in the label; With the mixture of CMCNa and PVP as short osmopolymer; And add an amount of acidic materials,, obtained gratifying sinomenine hydrochloride osmotic pump tablet like tartaric acid.And solved the drug release Time Delay that exists in the prior art.
For Pharmaceutical composition, exist complicated mutual relation between its various ingredients that contains, the variation of wherein a kind of component, content, even the variation of the mode of adding all possibly constitute influence to other components, and then influence the character of whole compositions.
The present invention provides a kind of osmotic pump controlled release tablet of sinomenine hydrochloride; Form by label, coating membrane and drug release hole; Label contains: sinomenine hydrochloride, acidic materials, short penetrating agent; The mixture of sodium carboxymethyl cellulose and polyvinylpyrrolidone is as short osmopolymer, and coating membrane contains: porogen and semipermeable membrane coating material.
Wherein, the weight percentage of each component is following in the label:
Wherein short penetrating agent is selected from sucrose, fructose, glucose, lactose, mannitol, sorbitol or their mixture, the mixture of preferred lactose and mannitol, and the weight ratio of further preferred lactose and mannitol is 1: 5～5: 1.
Its middle acid substance is selected from citric acid, tartaric acid, fumaric acid, succinic acid or malic acid, preferred tartaric acid, citric acid or malic acid.
Wherein coating membrane weight is the 2-10% of label weight.
Wherein the porogen in the coating membrane is a polyethylene glycol substances, preferred polyethylene glycol 1500～6000.
Wherein the weight percentage of porogen is the 5-50% of semipermeable membrane coating material in the coating membrane.
Wherein the semipermeable membrane coating material is the cellulose acetate class in the coating membrane.
The present invention also provides a kind of general method for preparing of sinomenine hydrochloride osmotic pump tablet, and step is following:
Label: each component is sieved respectively, mix homogeneously, the system soft material is granulated, drying, granulate, above-mentioned granule and mix lubricant is even, and compacting is in blocks,
Coating: porogen and semipermeable membrane coating material add in the solvent, are stirred to fully dissolving, promptly get coating solution, and label is carried out coating, when being the 2-10% of label weight to coating membrane weight till.Wherein solvent is selected from water, ethanol, acetone or dichloromethane.
Punching: at coated tablet one side perforating.
Investigate of the influence of various components below for osmotic pump tablet of the present invention:
1 different short penetrating agent are to the influence of drug release
The driving force of osmotic pump tablet release is the inside and outside permeable pressure head of coating membrane, and the osmotic pressure in the osmotic pump tablet coyote hole guarantees the evenly constant of release than the big 4 times of ability of the outer gastro-intestinal Fluid osmotic pressure of film, and therefore short penetrating agent is an adjuvant very important in the osmotic pump preparation.According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, fixing other components and consumption are investigated the influence of the short penetrating agent of variety classes to drug release rate, and the result sees accompanying drawing 1.
Sodium chloride is the most frequently used short penetrating agent; But itself and sinomenine hydrochloride can produce significant common-ion effect when coexisting; Obviously reduced the dissolubility of medicine, we also separate out this point sedimentary phenomenon and are able to confirm through in sinomenine hydrochloride solution, adding behind the certain density sodium chloride solution solution.The inventor has investigated multiple short penetrating agent; When with inorganic salts such as potassium sulfate during for short penetrating agent because the osmotic pressure that such inorganic salt was produced is less; So need to increase its consumption in label to guarantee the constant release of medicine; And when the inorganic salt large usage quantity poor compressibility behind the wet granulation, the friability of label is bigger, this is very unfavorable for follow-up coating operation.When using separately with sucrose, lactose, mannitol, fructose, glucose or its combination in any during, all can reach the purpose that makes medicine discharge the model release with zero level as short penetrating agent.Effect is best when especially making short penetrating agent with the mixture of lactose and mannitol.
The different amounts of 2 short penetrating agent is to the influence of drug release
Short penetrating agent works to regulate osmotic pressure in the coyote hole, and what of its consumption often are related to the zero level length of release time.According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample; The ratio of fixing other components and mannitol and lactose, the total amount of change mannitol and lactose, the microcrystalline Cellulose adjustment sheet is heavy; Investigate the influence of short penetrating agent different amounts to drug release, the result sees accompanying drawing 2.
It is thus clear that the consumption of short penetrating agent has appreciable impact to drug release rate, along with its consumption increases, release rate of drugs is accelerated, and the release behavior of medicine is more near the zero-order release model.Therefore, we are chosen in the short penetrating agent of adding about 63% in the prescription.
The different amounts of 3 short osmopolymer is to the influence of drug release
According to " preparation of sinomenine hydrochloride oral osmotic pump controlled-releasing tablet and release factors influencing " (Shenyang Pharmaceutical University's journal; 2003; 20 (3): a 165-169) literary composition; Investigate the influence of the consumption of short osmopolymer CMCNa, PVPP (crospolyvinylpyrrolidone) to drug release, thinking increases with the CMCNa consumption, and drug release is accelerated.And can see that by document Fig. 2 even be at the CMCNa consumption, the cumulative release degree of its 24h is merely about 80% at 8% o'clock.PVPP is the disintegrating agent of using always, swelling rapidly in water, and disintegrating property is superior, is called as super-disintegrant.Inventor of the present invention finds in practice; PVPP is when being applied to osmotic pump tablet, and the rapid expansion of tablet almost becomes spherical, causes breaking of coating membrane easily; Cause medicine to be dashed forward and release, run counter to the preparation osmotic pump tablet fully and hoped that control drug release reaches the original intention that zero level discharges.
Releasing properties according to the prepared sinomenine hydrochloride osmotic pump tablet of prescription of the present invention is shown is different with it.According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, fixing other components, the PVP adjustment sheet is heavy, investigates the influence of the different amounts of high molecular polymer CMCNa to rate of releasing drug and drug release process, and the result sees accompanying drawing 3.
Swelling formation gel takes place after meeting water in CMCNa, thereby can slow down drug release.Visible by accompanying drawing 3, the CMCNa drug release that can obviously slow down when reaching certain consumption, when consumption was 3% and 7%, drug release is slow excessively, and was undesirable.Label expands lessly when the CMCNa consumption is 3%, and coating membrane molecule gap is also less, because the gelatification of CMCNa makes moisture label more difficult to get access, so drug release is slower; Label expands obviously when consumption is 7%, and the part medicine is extruded from drug release hole, and causes coating membrane molecule gap to become big owing to expand, so drug release is to accelerate to some extent in 3% o'clock than consumption; The consumption drug release rate there was no significant difference that is 1% o'clock drug release rate when not using CMCNa, but the use of CMCNa can reduce the deviation of same lot sample article release degree, thus the inventor select to write out a prescription in the CMCNa of adding 0.5-2%.
PVP in label be binding agent be again short osmopolymer, the consumption when PVP is used as binding agent usually in label is below 5%, the very few effect that does not have binding agent of consumption; Too much the use meeting makes that when wet granulation soft material viscosity is excessive, can't granulate, even make granule reluctantly; Pellet hardness is excessive, and will cause can't tabletting, or institute's tabletting core is unfavorable for coating; Above say so adds PVP before wet granulation; After granulation, PVP added then and can not produce above phenomenon, but at this moment considered granule and the mixing uniformity problem that adds adjuvant again, unfavorable for the mixing uniformity of material when too much when adding adjuvant; The inventor with PVP carry out respectively Nei Jia with in add, its amount ranges is 3%～15%.
Through analyzing; The inventor thinks that why the present invention shows different releasing properties with sinomenine hydrochloride osmotic pump tablet in " preparation of sinomenine hydrochloride oral osmotic pump controlled-releasing tablet and release factors influencing ", is to have added acidic materials in the prescription of the present invention.
The different amounts of 4 acidic materials is to the influence of drug release
Sour environment can strengthen the dissolubility of sinomenine hydrochloride, and we add acidic materials to accelerate the rate of release of medicine in prescription.According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, fixing other components, PVP k30 adjustment sheet is heavy, investigates the influence of the consumption of acidic materials to drug release, and the result sees accompanying drawing 4.
It is thus clear that; Release rate of drugs is accelerated with the increase of prescription mesotartaric acid consumption, and promptly acid cosolvent has the significance influence to drug release, and is complete for guaranteeing drug release; The acidic materials that add 5-15% during we select to write out a prescription; Comprise tartaric acid, fumaric acid, citric acid, malic acid or succinic acid, wherein fumaric acid and succinic acid are flammable, and powder body and air can form explosive mixture; Consider to have drawback from industrial angle, so preferred tartaric acid, citric acid or malic acid among the present invention.
5 coating membranes are to the influence of the external release of Sinomenine hydrochloride controlled release sheet
5.1 coating membrane weight is to the influence of drug release
For the semipermeable membrane coating material in the coating membrane; Can be selected from various celluloses, like cellulose acetate class, ethyl cellulose class, two Palmic acid celluloses and polyvinyl alcohol, Merlon, polyoxyethylene etc.; All can realize the object of the invention, wherein preferred cellulose acetate class.
The coating membrane factor that influences the osmotic pump preparation drug release is mainly the consumption of porogen in coating membrane weight and the coating solution.Fixedly the consumption of porogen is 20% of a semipermeable membrane coating material consumption in the coating solution, according to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, investigates the influence of different coat weight to drug release, and the result sees accompanying drawing 5.
It is thus clear that coat weight has significance influence to drug release rate, under the certain situation of porogen consumption, along with the increase of coat weight, drug release rate obviously slows down, when coat weight be label weight 4% the time, the release in vitro degree is good.
5.2 the porogen consumption is to the influence of drug release in the coating solution
For the porogen in the coating membrane, can be selected from HPC, HPMC, Eudragit RL/RS, PVP, PEG, propylene glycol, sorbitol, micropowder lactose etc., all can realize the object of the invention, wherein preferred PEG class.
Except that coating membrane thickness, another key factor that influences drug release rate is the consumption of porogen in the coating solution, in order to reach ideal drug release rate; Increase along with porogen consumption in the coating solution; The also corresponding increase of the thickness of coating membrane, this just makes the technical process time lengthening, cost increases; And the porogen consumption is crossed and possibly caused medicine can't discharge fully at least or to reach when discharging fully coating membrane thickness too small in the coating solution; The latter will cause the coating time too short, make the coating thickness error of same lot sample article increase, and coating is lepthymenia causes the film rupture of dispose procedure underpants easily.According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample; The porogen consumption is respectively 10%, 20%, 30% of cellulose acetate consumption in the coating solution; The coating weightening finish is 4%; In addition, we have investigated the porogen consumption is to reach the sample coating thickness approaching with 20% release degree at 30% o'clock, and the result sees accompanying drawing 6.
It is thus clear that along with the increase of porogen PEG consumption in the coating membrane, drug release is significantly accelerated; Among the figure * (30%) curve representation porogen PEG consumption 30%; The sample release degree of coating weightening finish 9%, visible PEG consumption are that the weightening finish of 30% o'clock increase coating can reach the release degree approaching with the sample of PEG20%, but sample discharges not exclusively behind the former 12h; The consideration of time and cost in addition, we select, and the porogen consumption is 20% in the coating solution.
6 release degree and drug release behavior are investigated
6.1 dissolution medium is to the influence of drug release
One of advantage of osmotic pump preparation is that drug release rate is not influenced by the media environment pH value; According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, investigate the release degree of sample in 0.1M HCl, water, pH7.4 phosphate buffer and pH4.5 acetate buffer.The result sees accompanying drawing 7.
Visible by Fig. 7, in the dissolution medium of different pH value, the release degree of medicine does not have significant difference.
6.2 rotating speed is to the influence of drug release during drug release determination
Patient for all ages and classes, sex, health; Its gastrointestinal function can be different; For this reason, according to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, situation in the body of simulation different crowd; Measured the release degree situation of sample under different rotating speeds, the result sees accompanying drawing 8.
By Fig. 8 visible under different rotating speeds sample releases degree there was no significant difference, this also meets osmotic pump preparation and produces the principle that discharges power by osmotic pressure, the while can predict that medicine release degree difference in different human body is less.
6.3 release model match
According to above-mentioned " the general method for preparing of sinomenine hydrochloride osmotic pump tablet " preparation sample, the method working sample release degree according to above-mentioned " release in vitro degree mensuration " is described discharges degrees of data with gained and carries out the match of release mechanism, and the result sees table 1.
The mathematical model match of table 1 drug release rate curve
Visible by table 1, the release of osmotic pump tablet Chinese medicine is near the zero-order release model.
Description of drawings
The release of the medicine line of writing music when accompanying drawing 1 uses different short penetrating agent
◆ sodium chloride ▲ lactose ■ mannitol-lactose * sucrose-lactose
The release of the medicine line of writing music when accompanying drawing 2 uses the mannitol of different amounts-lactose
◆63％■30％▲15％
The release of the medicine line of writing music when accompanying drawing 3 uses the sodium carboxymethyl cellulose of different amounts
◆0％■1％▲3％×7％*2％
The release of the medicine line of writing music when accompanying drawing 4 uses the tartaric acid of different amounts
◆10％■5％▲0％×15％
The release of the medicine line of writing music during the different coatings weightening finish of accompanying drawing 5
◆ 2% ■ 4% ▲ 10% (the PEG consumption is 50% in the sample coating membrane of weightening finish 10%)
The release of the medicine line of writing music when using the Polyethylene Glycol of different amounts in accompanying drawing 6 coating membranes
◆10％■20％▲30％×(30％)
The release of the accompanying drawing 7 different medium Chinese medicines line of writing music
◆ 0.1M hydrochloric acid ▲ water ■ pH7.4 phosphate buffer * pH4.5 acetate buffer
The release of the medicine line of writing music during accompanying drawing 8 different rotating speeds
◆100r/min▲50r/min■25r/min
The specific embodiment
Following examples are to specify of the present invention, should not constitute restriction to scope of the present invention.
Embodiment 1, sinomenine hydrochloride weight are 22%, and acidic materials are 10%, and mannitol and lactose weight ratio are about 5: 1
The label prescription
Coating fluid prescription
Preparation technology:
Tabletting: raw material and adjuvant are crossed 100 mesh sieves respectively.Get the recipe quantity sinomenine hydrochloride,, add 50% ethanol system soft material, cross 24 mesh sieves and granulate, put drying in 45 ℃ of baking ovens, cross 22 mesh sieve granulate with mannitol, lactose, CMCNa, PVP k30, tartaric acid mix homogeneously.With above-mentioned granule and recipe quantity magnesium stearate mix homogeneously, compacting in flakes.
Coating: Macrogol 4000 is soluble in water, adds acetone, mix homogeneously.Get cellulose acetate and add in the above-mentioned mixed solution, be stirred to dissolving fully, promptly get coating solution.Label is carried out coating, is that coated tablet is dry till 4% o'clock of label weight to coating membrane weight.
Punching: adopt laser-beam drilling machine at coated tablet one side perforating.
Embodiment 2, sinomenine hydrochloride weight are 50%, and acidic materials are 15%, and mannitol and lactose weight ratio are 1: 1
Coating fluid prescription
Preparation technology:
Tabletting: raw material and adjuvant are crossed 100 mesh sieves respectively.Get the recipe quantity sinomenine hydrochloride,, add 50% ethanol system soft material, cross 24 mesh sieves and granulate, put drying in 45 ℃ of baking ovens, cross 22 mesh sieve granulate with mannitol, lactose, CMCNa, PVP k30, citric acid mix homogeneously.With PVP k30, the magnesium stearate mix homogeneously of above-mentioned granule and Extra Section, compacting in flakes.
Coating: polyethylene glycol 1500 is dissolved in the ethanol, adds dichloromethane, mix homogeneously.Get cellulose acetate and add in the above-mentioned mixed solution, be stirred to dissolving fully, promptly get coating solution.Label is carried out coating, is that coated tablet is dry till 10% o'clock of label weight to coating membrane weight.
Embodiment 3, sinomenine hydrochloride weight are 11%, and acidic materials are 5%, and mannitol and lactose weight ratio are about 1: 5
Coating fluid prescription
Preparation technology:
Method according to embodiment 2 replaces with malic acid with citric acid, tabletting.
Coating: Macrogol 2000 is dissolved in dichloromethane.Get cellulose acetate and add in the above-mentioned mixed solution, be stirred to dissolving fully, promptly get coating solution.Label is carried out coating, is that coated tablet is dry till 2% o'clock of label weight to coating membrane weight.
Coating fluid prescription
Preparation technology:
Method according to embodiment 1 replaces with citric acid with tartaric acid, tabletting.
Coating: polyethylene glycol 1500 is dissolved in the dichloromethane, adds acetone, mix homogeneously.Get cellulose acetate and add in the above-mentioned mixed solution, be stirred to dissolving fully, promptly get coating solution.Label is carried out coating, is that coated tablet is dry till 6% o'clock of label weight to coating membrane weight.
Embodiment 5, sinomenine hydrochloride weight are 11%, and acidic materials are 5%, and mannitol and lactose weight ratio are about 1: 2
Coating fluid prescription
Preparation technology:
According to the method for embodiment 1, tabletting.
Coating: polyethylene glycol 6000 is dissolved in the ethanol, adds acetone, mix homogeneously.Get cellulose acetate and add in the above-mentioned mixed solution, be stirred to dissolving fully, promptly get coating solution.Label is carried out coating, is that coated tablet is dry till 8% o'clock of label weight to coating membrane weight.
Comparative Examples, according to " preparation of sinomenine hydrochloride oral osmotic pump controlled-releasing tablet and release factors influencing " disclosed prescription: sinomenine hydrochloride, sodium chloride, CMCNa, PVPP, tabletting is granulated, coating.Wherein, added the part lactose and weighed with adjustment sheet in order to have comparability with embodiments of the invention.Write out a prescription as follows:
Coating fluid prescription
According to 165 pages of disclosed method preparations of the document.
Detect the friability of the product that embodiment 1-5 and Comparative Examples obtain according to following method:
Get 12 of labels, blow away the powder that comes off with hair-dryer, precision is weighed, and puts in the cylinder, rotates 100 times.Take out, remove powder with method, precision is weighed, and subtract weight loss and must not cross 1%, and the sheet that must not detect fracture, be full of cracks and pulverize.
Testing result:
Investigate the release in vitro situation of sinomenine hydrochloride osmotic pump tablet according to following method:
Two appendix X of Pharmacopoeia of the People's Republic of China version in 2010 D, first method adopts X C second subtraction unit, is dissolution medium with the 900ml distilled water, rotating speed 50r/min; 37 ℃ of temperature, respectively at 1,2,4; 6,8,12,14; 16,18,24h gets dissolution fluid 6ml (adding dissolution medium 6ml simultaneously), filters.Get subsequent filtrate according to ultraviolet spectrophotometry (two appendix IVA of Pharmacopoeia of the People's Republic of China version in 2010), measure absorbance, calculate the cumulative release percentage rate of each time point according to standard curve in the 265nm wavelength.
With sodium chloride during as short penetrating agent, not only friability is defective in the visual contrast example, and its external stripping is also defective.
Claims (12)
1. the osmotic pump controlled release tablet of a sinomenine hydrochloride; Form by label, coating membrane and drug release hole; It is characterized in that label contains: sinomenine hydrochloride, acidic materials, short penetrating agent; The mixture of sodium carboxymethyl cellulose and polyvinylpyrrolidone is as short osmopolymer, and coating membrane contains: porogen and semipermeable membrane coating material.
2. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that the weight percentage of each component is following in the label:
3. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that short penetrating agent is selected from sucrose, fructose, glucose, lactose, mannitol, sorbitol or their mixture.
4. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 3 is characterized in that short penetrating agent is the mixture of lactose and mannitol.
5. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 4, the weight ratio that it is characterized in that lactose and mannitol is 1: 5～5: 1.
6. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that acidic materials are selected from citric acid, tartaric acid, fumaric acid, succinic acid or malic acid.
7. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that coating membrane weight is the 2-10% of label weight.
8. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that the porogen in the coating membrane is a polyethylene glycol substances.
9. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 8 is characterized in that described polyethylene glycol substances is selected from polyethylene glycol 1500～6000.
10. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1, the weight percentage that it is characterized in that porogen in the coating membrane is the 5-50% of semipermeable membrane coating material.
11. the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1 is characterized in that the semipermeable membrane coating material is the cellulose acetate class in the coating membrane.
12. a method for preparing the osmotic pump controlled release tablet of sinomenine hydrochloride as claimed in claim 1, step is following:
Label: each component is sieved respectively, mix homogeneously, the system soft material is granulated, drying, granulate, above-mentioned granule and mix lubricant is even, and compacting is in blocks,
Coating: porogen and semipermeable membrane coating material add in the solvent, are stirred to fully dissolving, promptly get coating solution, and label is carried out coating, when being the 2-10% of label weight to coating membrane weight till,
Punching: at coated tablet one side perforating.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109394732A (en) * | 2017-08-16 | 2019-03-01 | 安徽中医药大学 | Sinomenine enteric positions osmotic pump controlled release capsule and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109394732A (en) * | 2017-08-16 | 2019-03-01 | 安徽中医药大学 | Sinomenine enteric positions osmotic pump controlled release capsule and preparation method thereof |
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Application publication date: 20120919 |