CN103784412A - Icotinib hydrochloride dispersible tablet and preparation method thereof - Google Patents
Icotinib hydrochloride dispersible tablet and preparation method thereof Download PDFInfo
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- CN103784412A CN103784412A CN201410017279.4A CN201410017279A CN103784412A CN 103784412 A CN103784412 A CN 103784412A CN 201410017279 A CN201410017279 A CN 201410017279A CN 103784412 A CN103784412 A CN 103784412A
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Abstract
The invention discloses an icotinib hydrochloride dispersible tablet and a preparation method and applications thereof. The icotinib hydrochloride dispersible tablet disclosed by the invention is composed of the components in percentage by weight: 5-50% of icotinib hydrochloride, 10-40% of a filling agent, 10-55% of a disintegrating agent, 10-50% of an acidifying agent, 0.1-15% of an adhesive, and 0.1-20% of a lubricant and a flow aid. Compared with common tablets, the icotinib hydrochloride dispersible tablet disclosed by the invention does not contain a surfactant, is good in solubility, dispersibility and disintegrative property, and can be completely disintegrated within 1 minute. The icotinib hydrochloride dispersible tablet prepared by using the method disclosed by the invention is high in dissolution rate, high in bioavailability, rapid in in-vivo distribution, stable in quality, good in taste, simple and practicable in preparation method, and suitable for industrial production.
Description
Invention field
The present invention relates to chemical pharmacy field, be specifically related to a kind of hydrochloric acid Conmana dispersible tablet and preparation method thereof.
Background of invention
Show according to the Chinese Third National coroner's inquest that in April, 2008, China's Ministry of Public Health was issued, malignant tumor accounts for the first place of the city cause of death, and the first place that pulmonary carcinoma is Death Causes of Tumor accounts for 22.7% of whole mortality of malignant tumors sums, and being obvious ascendant trend, Past 30 Years has risen 46.5%.Britain name oncologist R.Peto prophesy: if can not get timely control, will exceed 1,000,000 to the annual pulmonary carcinoma number of China in 2025, and become the first in the world pulmonary carcinoma big country.
The molecular targeted therapy (Molecular targeted therapy) of tumor is using the specific molecular in tumor cell as target spot, utilize the biological function of this target spot of molecular targeted agents energy specific inhibition, thereby from the malignant behaviors of molecular level reversing tumor cell, reaching the object that suppresses tumor growth, is the field that has vigor most in recent years, receives much attention.Molecular targeted agents mainly contains EGF-R ELISA (EGFR) family group inhibitor etc.
170 kilodaltons (kDa) membrane bound protein that EGF-R ELISA (EGFR) is expressed for surface epithelial cell.EGFR belongs to the growth factor receptors family of protein tyrosine kinase.EGFR is the protein that growth promotes oncogene erbBErbB or erbBl, and it be a member of the ERBB family of family's proto-oncogene (protooncogenes), it is believed that in the generation of the many cancers of the mankind with in developing and plays a crucial role.Especially in breast carcinoma, bladder cancer, pulmonary carcinoma and glioblastoma, observed the expression that EGFR strengthens.Relevant transmembrane receptor, i.e. EGFR, HER-2/neu (erbB2), HER-3 (erbB3) and HER-4 (erbB4) in four kinds of structures of ERBB family coding of oncogene.Clinically, the amplification of ERBB oncogene and/or receptor overexpression in existing report tumor are relevant with patient's poor prognosis to disease palindromia, and to the relevant (L.Harris etc. of response of therapy, 1999, Int.J.Biol.Markers, 14:8-15 and J.Mendelsohn and J.Baselga, 2000, Oncogene, 19:6550-6565).
The combination activation signal Signal Transduction Pathways of EGF or TGF-α and EGFR and cause cell proliferation.Dimerization, conformation change and the internalization of EGFR molecule plays signal in transfer cell, causes cell cycle regulation.Affect growth factor receptor function and regulate or cause the hereditism of receptor and/or part overexpression to change, cause cell proliferation.In addition, determine that EGFR is at (the M.-J.Oh etc. that work aspect the enhancing of cell differentiation, cell mobility, protein secreting, neovascularization, invasion, transfer and the drug resistance of cancerous cell to chemotherapeutant and lonizing radiation, 2000, Clin.Cancer Res., 6:4760-4763).
Hydrochloric acid Conmana (Icotinib Hydrochloride) is oral EGFR tyrosine kinase inhibitor, reaches Pharmaceutical (Beta) exploitation by Chinese shellfish, by CFDA approval listing, is mainly used in treating nonsmall-cell lung cancer in June, 2011.Preclinical study demonstration, hydrochloric acid Conmana is a kind of efficient specific epidermal growth factor recipient tyrosine kinase inhibitor (EGFR-TKI).In to 85 kinds of kinase whose examinations, hydrochloric acid Conmana forcefully selectivity suppresses EGFR and 3 mutants thereof, but to remaining 81 kinds of kinases all without obvious inhibitory action.
Two recent I/II a clinical trial phases are studied for curative effect and the safety of hydrochloric acid Conmana treatment advanced Non-small cell lung (NSCLC).This medicine is compared with erlotinid hydrochloride with external two medicine Ji Feiteni that gone on the market at present, similar at aspects such as chemical constitution, molecular mechanisms of action, curative effects, but has better safety.
Sell in existing market is only hydrochloric acid Conmana ordinary tablet, and the coating materials of its use comprises surfactant, and body is had to certain zest, and hydrochloric acid Conmana dispersible tablet provided by the invention has also improved its bioavailability simultaneously.
Summary of the invention
The invention provides a kind of new hydrochloric acid Conmana dispersible tablet, is that the interpolation surfactant existing according to existing hydrochloric acid Conmana ordinary tablet has the problems such as stimulation, bioavailability are not high to body.The invention provides a kind of hydrochloric acid Conmana dispersible tablet, adopt acidulant by its parcel or parcel mutually, thereby reach the effect of embedding, and through repetition test by each component screening to weight ratio of the present invention, the dispersible tablet steady quality obtaining, stripping is fast, in body, distributes rapidly, and bioavailability is high, dispersibility, disintegrative are good, can disintegrate in 1 minute complete, and this product is containing surfactant, and can reduce stimulates body.
On the one hand, the invention provides a kind of hydrochloric acid Conmana dispersible tablet, it comprises as follows according to the component of percetage by weight meter: hydrochloric acid Conmana 5～50%, filler 10～40%, disintegrating agent 10～55%, acidulant 10～50%, binding agent 0.1～15%, lubricant and fluidizer 0.1～20%.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, it comprises as follows according to the component of percetage by weight meter: hydrochloric acid Conmana 25%, filler 30%, disintegrating agent 30%, acidulant 10%, binding agent 2%, lubricant and fluidizer 3%.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described filler is a kind of in starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol, sorbitol or xylitol or their mixture.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described disintegrating agent is a kind of in microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, crosslinked carboxymethyl fecula sodium, dried starch or their mixture.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described acidulant is a kind of in citric acid, lactic acid, acetic acid, ethanedioic acid, malonic acid, succinic acid, tartaric acid, adipic acid, malic acid, nicotinic acid, pectic acid, ascorbic acid, caffeic acid, fumaric acid, maleic acid, phosphoric acid solution or their mixture.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described binding agent is a kind of in hypromellose, sodium carboxymethyl cellulose, starch, pregelatinized Starch, polyvidone, gelatin, Polyethylene Glycol, ethanol, water or their mixture.
Some embodiments therein, hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described lubricant and fluidizer are a kind of of micropowder silica gel, magnesium stearate, silicon dioxide, Pulvis Talci, Polyethylene Glycol apoplexy due to endogenous wind or their mixture.
On the other hand, the present invention relates to a kind of preparation method of hydrochloric acid Conmana dispersible tablet, it comprises the steps: that (1) sieve hydrochloric acid Conmana and pharmaceutic adjuvant respectively; Binding agent be dissolved in concentration be 85% or following alcoholic solution or aqueous solution in after, then the acidulant of recipe quantity is dissolved in the solution containing binding agent, obtain acid solution; (2) hydrochloric acid Conmana is mixed homogeneously with filler, disintegrating agent, fluidizer after adopting the made acid solution embedding of step (1), adds binding agent, mixes, and makes soft material; (3) soft material is crossed to 14～30 mesh sieves, 40～60 ℃ dry, 14～30 order granulate; (4) add lubricant, mix homogeneously; (5) tabletting, makes hydrochloric acid Conmana dispersible tablet.
Some embodiments therein, the preparation method of hydrochloric acid Conmana dispersible tablet of the present invention, wherein, described in step (2), be that hydrochloric acid Conmana and acid solution are passed through to fluid bed embedding with acid solution embedding, or hydrochloric acid Conmana is put into colloid mill together with acid solution and shear, drier.
The prescription ratio of hydrochloric acid Conmana dispersible tablet of the present invention is not by teaching material or other reference material gained, but by the testing program gained conforming with the regulations in a large number, made dispersible tablet has carried out quality research, meets " Chinese Pharmacopoeia " 2010 editions two and make by oneself about dispersible tablet and other requirement of quality standard.In research, find the obvious existing conventional tablet of dissolution of technical solution of the present invention.
Compared with prior art, the present invention has following beneficial effect:
(1) hydrochloric acid Conmana is made tablet formulation by the present invention, belongs to the whole world pioneering, can improve like this its bioavailability;
(2) the present invention granulates after adopting acidulant to process in the preparation of hydrochloric acid Conmana dispersible tablet, greatly improves its bioavailability;
(3) tablet formulation that the present invention makes, compared with ordinary tablet, stripping is rapid, and disintegrative is good, and disintegrate completely in 2 minutes absorbs soon, and bioavailability is high, stable in properties;
(4) tablet formulation that the present invention makes, does not use surface active agent solubilization in manufacturing process, reduce body is stimulated, and has reduced the untoward reaction of medicine, has increased patient's compliance.
Excipient of the present invention comprises, but be not limited to, ion-exchanger, aluminum, aluminium stearate, lecithin, serum albumin, as human albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, the partial glycerol ester admixture of saturated vegetable fatty acid, water, salt or electrolyte, as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloid silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, polyethylene-polyoxypropylene-blocking-up polymer, lanoline, sugar, as lactose, dextrose plus saccharose, starch is as corn starch and potato starch, the derivant of cellulose and it is as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate, natural gum powder, Fructus Hordei Germinatus, gelatin, Pulvis Talci, adjuvant is as cocoa butter and suppository wax, oily as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum Sesami, olive oil, Semen Maydis oil and Oleum Glycines, glycols compound, as propylene glycol and Polyethylene Glycol, esters is as ethyl oleate and ethyl laurate, agar, buffer agent is as magnesium hydroxide and aluminium hydroxide, alginic acid, pyrogen-free water, Deng oozing salt, Lin Ge (family name) solution, ethanol, phosphate buffer solution, and other nontoxic proper lubrication agent are as sodium laurylsulfate and magnesium stearate, coloring agent, releasing agent, coating dress material, sweeting agent, flavoring agent and spice, antiseptic and antioxidant.
Pharmaceutical composition of the present invention can also optionally contain one or more diluent.The example of diluent comprises mannitol, sorbitol, biphosphate calcium dihydrate, microcrystalline Cellulose and efflorescence cellulose.Preferred diluent is microcrystalline Cellulose.Microcrystalline Cellulose can be obtained from several suppliers, comprises Avicel PH101, Avicel PH102, Avicel PH103, Avicel PH105 and Avicel PH200 that FMC Corporation manufactures.
Pharmaceutical composition of the present invention can also optionally contain disintegrating agent.Disintegrating agent can be the one in several modified starches, modified cellulose polymer or polycarboxylic acids, such as crosslinked Carboxymethyl cellulose sodium, Explotab, polacrilin potassium and calcium carboxymethylcellulose (CMCCalcium).In one embodiment, disintegrating agent is croscarmellose sodium.Croscarmellose sodium NF type A obtains with trade name " Ac-di-sol " on market.
Pharmaceutical composition of the present invention can also optionally contain one or more surfactants or wetting agent.Surfactant can be anion, cation or neutral surface active agent.Anion surfactant comprises sodium lauryl sulfate, dodecyl sodium sulfate, oleyl sodium sulfate and the sodium laurate mixing with stearate and Talcum.Cationic surfactant comprises benzalkonium chloride and alkyl trimethyl ammonium bromide.Neutral surface active agent comprises glycerol list olein, polyoxyethylene sorbitan fatty acid ester, polyvinyl alcohol and anhydro sorbitol fat.The embodiment of wetting agent comprises poloxamer, polyoxyethylene alkyl ether, castor oil derivatives and polyoxyethylene 8 stearate fat.
The present invention can also optionally join antioxidant in preparation, thereby gives its chemical stability.Antioxidant is selected from the extract of a-tocopherol, Y-tocopherol, S-tocopherol, tocopherol enrichment natural origin, sodium or calcium salt, the Vitamin C acyl cetylate of L-AA and it, amass wealth by heavy taxation propyl propionate, amass wealth by heavy taxation misery ester, amass wealth by heavy taxation sour dodecyl ester, Yoshinox BHT (BHT) and butylated hydroxyanisol (BHA).In one embodiment, antioxidant is BHT or BHA.
The preferred dosage form of drug composition of the present invention is the tablet of preparing by compression method.Described tablet can carry out film with the mixture such as hydroxypropyl cellulose and hydroxypropyl emthylcellulose, contains titanium dioxide and/or other coloring agent, such as ferrum oxide, dyestuff and Se Dian in this mixture; The mixture of polyvinyl alcohol (PVA) and Polyethylene Glycol (PEG), contains titanium dioxide and/or other coloring agent, such as ferrum oxide, dyestuff and Se Dian; Or any other suitable instant-free coating agent.Coating provides taste masked and other stability to final tablet.What commercially available film provided for Colorcon is preparation mixture of powders
.
The present invention can also add sweeting agent and/or fumet.
The specific embodiment
Further explain the present invention below in conjunction with embodiment, but embodiment does not limit in any form to the present invention.
Embodiment 1
Hydrochloric acid Conmana 250g
Lactose 120g
Crospolyvinylpyrrolidone 25g
Carboxymethylstach sodium 50g
Hydroxypropyl methylcellulose 4g
Micropowder silica gel 15g
Magnesium stearate 10g
Water 60g
95% ethanol 122g
Make 1000.
Preparation method:
Step 1: the hydrochloric acid Conmana of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and hydroxypropyl methylcellulose first uses hot water swelling, is stirred to dissolving, then adds ethanol, makes concentration of alcohol reach 70%.
Step 2: by recipe quantity, hydrochloric acid Conmana, lactose, polyvinylpolypyrrolidone, micropowder silica gel are mixed to equal Uniform, add the solution of hypromellose described in step 1 to make soft material.
Step 3: made soft material in step 2 is crossed to 18 mesh sieves and granulate, 50 ℃ dry, and moisture is 2.7%, 18 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains hydrochloric acid Conmana dispersible tablet.
Embodiment 1 dispersible tablet smooth in appearance, dispersibility meets relevant regulations, but dissolution is poor.
Embodiment 2
Hydrochloric acid Conmana 250g
Lactose 80g
Crospolyvinylpyrrolidone 14g
Carboxymethylstach sodium 20g
Hydroxypropyl methylcellulose 4g
Citric acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 250
95% ethanol 125g
Make 1000.
Preparation method:
Step 1: the hydrochloric acid Conmana of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and hydroxypropyl methylcellulose first uses hot water swelling, is stirred to dissolving, then adds ethanol, makes concentration of alcohol reach 70%.Separately get above-mentioned hydroxypropyl methylcellulose solution 50g, add 170g water, add citric acid mix homogeneously.
Step 2: recipe quantity hydrochloric acid Conmana is mixed homogeneously with recipe quantity lactose, crospolyvinylpyrrolidone, carboxymethylstach sodium, micropowder silica gel after the embedding of fluid bed acid solution with citric acid solution in step 1, adds described in step 1, to remain hypromellose solution and make soft material.
Step 3: made soft material in step 2 is crossed to 16 mesh sieves and granulate, 50 ℃ dry, and moisture is 2.5%, 16 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains hydrochloric acid Conmana dispersible tablet.
Embodiment 2 has added acidulant, has reduced the amount of disintegrating agent, and technique is optimized on the basis of embodiment 1, after first acidification, granulates again, finds dispersible tablet smooth in appearance, and dissolution is better, but dispersibility is general, disintegrate completely in 3min.
Embodiment 3
Hydrochloric acid Conmana 250g
Crospolyvinylpyrrolidone 40g
Carboxymethylstach sodium 40g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 250
95% ethanol 125g
Make 1000.
Preparation method is with embodiment 2.
Implementing 3 increases crospolyvinylpyrrolidone, carboxymethylstarch sodium content, and dispersible tablet dispersibility meets 2010 editions pharmacopeia requirements, and dissolution is better.
Embodiment 4
It is identical that embodiment 4 and embodiment 3 write out a prescription, and selects different acidify embedding modes, and hydrochloric acid Conmana and acidulant solution are put into colloid mill and sheared, then spraying is dry.The indices of dispersible tablet and the embodiment 3 made dispersible tablet there was no significant difference of writing out a prescription.
Embodiment 5
Hydrochloric acid Conmana 250g
Lactose 80g
Crospolyvinylpyrrolidone 30g
Carboxymethylstach sodium 50g
Starch 3.5g
Citric acid 70g
Malic acid 30g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 370g
Make 1000.
Preparation method:
Step 1: the hydrochloric acid Conmana of having pulverized and pharmaceutic adjuvant are crossed respectively to 120 mesh sieves, and starch adds water and makes starch slurry.Get the starch slurry 50g preparing, stir and add 180g water, then add citric acid, mix equal Uniform.
Step 2: recipe quantity hydrochloric acid Conmana is mixed homogeneously with recipe quantity lactose, crospolyvinylpyrrolidone, carboxymethylstach sodium, micropowder silica gel, malic acid after the embedding of fluid bed acid solution with part acid solution in step 1, adds remaining starch slurry described in step 1 to make soft material.
Step 3: made soft material in step 2 is crossed to 24 mesh sieves and granulate, 60 ℃ dry, and moisture is 2.8%, 24 mesh sieve granulate.
Step 4: mix homogeneously with magnesium stearate making granule in step 3.
Step 5: semi-finished product detect, and determine sheet weight, and tabletting, obtains hydrochloric acid Conmana dispersible tablet.
Embodiment 5 starch in replace hydroxypropyl methylcellulose, all the other are constant, find that made dispersible tablet hardness declines to some extent at equal pressure condition lower sheeting, but also meet 2010 editions pharmacopeia dispersible tablet standards.
Embodiment 6
Hydrochloric acid Conmana 250g
Starch 80g
Crospolyvinylpyrrolidone 25g
Carboxymethylstach sodium 50g
Hydroxypropyl methylcellulose 3g
Oxalic acid 100g
Micropowder silica gel 15g
Magnesium stearate 8g
Water 250g
95% ethanol 125g
Make 1000.
Preparation method is with embodiment 2.
Embodiment 6 changes filler, and replace lactose with starch, and oxalic acid is replaced to citric acid, the made dispersible tablet there was no significant difference of dispersible tablet and embodiment 3, dispersibility and dissolution are all better.
Embodiment 7
Hydrochloric acid Conmana 250g
Icing Sugar 80g
Crospolyvinylpyrrolidone 25g
Carboxymethylstach sodium 50g
Hydroxypropyl methylcellulose 3.5g
Citric acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 250g
95% ethanol 125g
Make 1000.
Preparation method is with implementing 2.
Embodiment 7 changes filler, replaces lactose with Icing Sugar, all the other with embodiment 3 together, the made dispersible tablet there was no significant difference of dispersible tablet and embodiment 3, dispersibility and dissolution are all better.
Embodiment 8
Hydrochloric acid Conmana 250g
Starch 80g
Crospolyvinylpyrrolidone 25g
Carboxymethylstach sodium 50g
Hydroxypropyl methylcellulose 3.5g
Malic acid 100g
Micropowder silica gel 15g
Magnesium stearate 7.5g
Water 255g
95% ethanol 120g
Make 1000.
Preparation method is with embodiment 7.
The made dispersible tablet smooth in appearance of embodiment 8, dissolution are good, and dispersibility is slightly poorer than adopting the dispersible tablet of citric acid, but adopts the dispersible tablet of oxalic acid to get well.
Biological test
(1) table 1 is for selling the dissolution comparative result of hydrochloric acid Conmana ordinary tablet in hydrochloric acid Conmana dispersible tablet and market.
With reference to dissolution method (2010 editions two appendix XC bis-methods of Chinese Pharmacopoeia).
The comparison of ordinary tablet cumulative percentage dissolution is sold in table 1 hydrochloric acid Conmana dispersible tablet and market
As can be seen from Table 1, the dissolution in vitro of hydrochloric acid Conmana dispersible tablet in 10-30min is obviously better than ordinary tablet.
(2) hydrochloric acid Conmana dispersible tablet assay
Measure with reference to high-efficient liquid phase technique (two appendix VD of Chinese Pharmacopoeia version in 2010).
Table 2 hydrochloric acid Conmana dispersible tablet assay
| Batch | Hydrochloric acid Conmana dispersible tablet content (%) |
| Batch 1 | 100.56 |
| Batches 2 | 100.21 |
| Batches 3 | 100.34 |
As can be seen from Table 2, the content of the hydrochloric acid Conmana dispersible tablet requirement that conforms with the regulations.
(3) the quality stability comparison of hydrochloric acid Conmana dispersible tablet
Hydrochloric acid Conmana dispersible tablet accelerated test: the hydrochloric acid Conmana dispersible tablet of blister package is put under 2 ℃ of 40 ℃ of scholars of temperature, relative humidity 75% scholar's 5% condition and placed six months, outcome quality is stable, and indices is as shown in table 3.
Six months accelerated test testing results of table 3 hydrochloric acid Conmana dispersible tablet
| Inspection batch | Outward appearance | Disintegration | Dispersing uniformity | Dissolution % | Content % |
| Batch 1 | Faint yellow smooth | 39 | Conform with the regulations | 101.01 | 109.97 |
| Batches 2 | Faint yellow smooth | 42 | Conform with the regulations | 100.23 | 100.14 |
| Batches 3 | Faint yellow smooth | 40 | Conform with the regulations | 99.98 | 99.98 |
Claims (9)
1. a hydrochloric acid Conmana dispersible tablet, it comprises as follows according to the component of percetage by weight meter: hydrochloric acid dust gram ° Buddhist nun 5～50%, filler 10～40%, disintegrating agent 10～55%, acidulant 10～50%, binding agent 0.1～15%, lubricant and fluidizer 0.1～20%.
2. hydrochloric acid Conmana dispersible tablet according to claim 1, it comprises as follows according to the component of percetage by weight meter: hydrochloric acid Conmana 25%, filler 30%, disintegrating agent 30%, acidulant 10%, binding agent 2%, lubricant and fluidizer 3%.
3. hydrochloric acid Conmana dispersible tablet according to claim 1, wherein, described filler is a kind of in starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol, sorbitol or xylitol or their mixture.
4. hydrochloric acid Conmana dispersible tablet according to claim 1, wherein, described disintegrating agent is a kind of in microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, crosslinked carboxymethyl fecula sodium, dried starch or their mixture.
5. hydrochloric acid Conmana dispersible tablet according to claim 1, wherein, described acidulant is a kind of in citric acid, lactic acid, acetic acid, ethanedioic acid, malonic acid, succinic acid, tartaric acid, adipic acid, malic acid, nicotinic acid, pectic acid, ascorbic acid, caffeic acid, fumaric acid, maleic acid, phosphoric acid solution or their mixture.
6. hydrochloric acid Conmana dispersible tablet according to claim 1, wherein, described binding agent is a kind of in hypromellose, sodium carboxymethyl cellulose, starch, pregelatinized Starch, polyvidone, gelatin, Polyethylene Glycol, ethanol, water or their mixture.
7. hydrochloric acid Conmana dispersible tablet according to claim 1, wherein, described lubricant and fluidizer are a kind of of micropowder silica gel, magnesium stearate, silicon dioxide, Pulvis Talci, Polyethylene Glycol apoplexy due to endogenous wind or their mixture.
8. a preparation method for hydrochloric acid Conmana dispersible tablet described in any one claim in claim 1-7, it comprises the steps: that (1) sieve hydrochloric acid Conmana and pharmaceutic adjuvant respectively; Binding agent be dissolved in concentration be 85% or following alcoholic solution or aqueous solution in after, then the acidulant of recipe quantity is dissolved in the solution containing binding agent, obtain acid solution; (2) hydrochloric acid Conmana is mixed homogeneously with filler, disintegrating agent, fluidizer after adopting the made acid solution embedding of step (1), adds binding agent, mixes, and makes soft material; (3) soft material is crossed to 14～30 mesh sieves, 40～60 ℃ dry, 14～30 order granulate; (4) add lubricant, mix homogeneously; (5) tabletting, makes hydrochloric acid Conmana dispersible tablet.
9. the preparation method of hydrochloric acid Conmana dispersible tablet according to claim 8, wherein, described in step (2), be that hydrochloric acid Conmana and acid solution are passed through to fluid bed embedding with acid solution embedding, or hydrochloric acid Conmana put into colloid mill together with acid solution and shear, drier.
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| CN104997745A (en) * | 2015-08-18 | 2015-10-28 | 上海韬鸿化工科技有限公司 | Alpha-crystal form imatinib mesylate dispersible tablets and preparation method thereof |
| CN104997745B (en) * | 2015-08-18 | 2018-04-27 | 和龙 | A kind of alpha-crystal form imatinib mesylate dispersible tablet and preparation method thereof |
| CN111888477A (en) * | 2020-09-15 | 2020-11-06 | 北京福元医药股份有限公司 | Bedaquinoline pharmaceutical preparation |
| CN111888477B (en) * | 2020-09-15 | 2023-03-07 | 北京福元医药股份有限公司 | Bedaquinoline pharmaceutical preparation |
| CN114504577A (en) * | 2022-02-15 | 2022-05-17 | 上海龙翔生物医药开发有限公司 | Preparation method of EGFR (epidermal growth factor receptor) molecular targeted antitumor drug |
| WO2023155321A1 (en) * | 2022-02-15 | 2023-08-24 | 上海龙翔生物医药开发有限公司 | Method for preparing egfr-molecule-targeted anti-tumor drug |
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Application publication date: 20140514 |