CN1634048A - Berberine hydrochloride granule for masking flavor and its preparation - Google Patents
Berberine hydrochloride granule for masking flavor and its preparation Download PDFInfo
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- CN1634048A CN1634048A CN 200410090676 CN200410090676A CN1634048A CN 1634048 A CN1634048 A CN 1634048A CN 200410090676 CN200410090676 CN 200410090676 CN 200410090676 A CN200410090676 A CN 200410090676A CN 1634048 A CN1634048 A CN 1634048A
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Abstract
The invention discloses a berberine hydrochloride granule for masking flavor and its preparation which comprises flavor concealing dressing material and berberine hydrochloride bundled therein, wherein the total amount of berberine hydrochloride is 45-65% of the total amount of flavor concealing berberine hydrochloride, the preparation comprises, (1) film forming material, selected from one or more of Eudragit E100, Eudragit EPO, Eudragit L100, and methyl hydroxypropylcellulose, which amounts to 70-80% of the total weight of the flavor concealing dressing material, (2) plasticizing agent, which is selected from one or more of PEG6000, dibutyl sebacate, triethyl citrate, whose amount is 5-15% of the total weight of the flavor concealing dressing material, (3) antistatic agent selected from one or more of magnesium stearate, talcum powder, micro powder silica gel, whose amount is 5-15% of the total weight of the flavor concealing dressing material.
Description
Technical field
The present invention relates to berberine hydrochloride granule for masking flavor and preparation thereof, more specifically say so, cover the disagreeable taste of berberine hydrochloride, and this preparation of granules is become the good and high preparation of dissolubility of mouthfeel, belong to the pharmaceutics field by the method coating berberine hydrochloride of spraying.
Background technology
Berberine hydrochloride is a kind of broad spectrum antimicrobicide, and is all inhibited to Gram-positive and gram negative bacteria, wherein to Hemolytic streptococcus, the gold Fructus Vitis viniferae, vibrio cholera, meningococcus, Shigella, Bacillus typhi, diphtheria corynebacterium etc. all have the good restraining effect.In recent years, many scholars have also carried out deep research to the otherwise application of berberine hydrochloride as treatment hypertension, diabetes etc.
Berberine hydrochloride has quite long history in the clinical practice of China, and safe in utilization, and curative effect is reliable.Berberine hydrochloride is in irreplaceable status in the antibacterial that the child can use.The berberine hydrochloride taste is extremely bitter, uses traditional handicraft, during as employing sugar coating or gastric solubleness film-coat or capsule formulation, child, old age, bed and dysphagia patients and particular patients ' medication is brought problem.Child, gerontal patient, sickbed patients and dysphagia patients can be because of tablet or capsule volume excessive appearance card larynx or cough and choke phenomenons, take if tablet done to fragmentate or capsule taken apart, then can't avoid the bitterness problem; And diabetics is taken and is contained the high coated tablet of sugar or come the preparation of flavoring because of adding a large amount of sweeting agents, then can produce harmful effect to patient's the state of an illness.
Conventional formulation technology causes the patient to use the compliance of berberine hydrochloride very poor, thereby has had a strong impact on the performance of berberine hydrochloride therapeutical effect, and its clinical practice also is restricted.Therefore the patient wish to obtain to be liquid, can be in the oral cavity the dispersive berberine hydrochloride novel formulation that maybe can chew rapidly.
At application number is to propose in 99813800.2 the patent documentation to come the coating ibuprofen by the solution with ethyl cellulose and hydroxypropyl methylcellulose by the method for spraying, though the ibuprofen granule taste through coating obtains covering, but cellulosic polymer permeability and dissolubility under all pH value is very low, causes drug effect to reduce.
At application number is to propose in 00812588.0 the patent documentation by add the release problem that film disintegrating agent (cross-linking sodium carboxymethyl cellulose) solves cellulosic polymer in coating material; but because add film disintegrating agent (cross-linking sodium carboxymethyl cellulose); taste masked particle can or absorb water 30 times of back expansions in the oral cavity and not dissolve; become the large volume porous particle; can't form colloidal solution; coated drugs is oozed out, so can't reach the purpose of covering the medicine taste in the hole.Simultaneously can't suitability for industrialized production because of difficult quality control between criticizing and criticizing.
At application number is that the drug powder of coating material coating in 00114205.4 the patent documentation is between the 40-100 order, particle grain size is bigger, can't prepare meet that two appendix IO of Pharmacopoeia of People's Republic of China version in 2000 require be liquid, can the dispersive pharmaceutical preparation that maybe can chew rapidly in the oral cavity.
Summary of the invention
Primary and foremost purpose of the present invention provides a kind of berberine hydrochloride granule for masking flavor, and its tool palatability has been covered the bitterness of berberine hydrochloride, and reducing taste bud stimulates; The suspension that its granularity can be used as rapid dispersive dosage form under the effect of saliva in the oral cavity or the dosage form that can directly chew or can directly drink.
Second purpose of the present invention provides with berberine hydrochloride granule for masking flavor and adds the preparation that mouthfeel is good, dissolubility is high that excipient is made.
The objective of the invention is to solve by following scheme:
The medicine of coating is a berberine hydrochloride.
Directly with rotating fluidized bed coating machine berberine hydrochloride is wrapped one deck coatings uniformly, make berberine hydrochloride granule for masking flavor, this particulate granularity is 50～2000 μ m, preferred 200～800 μ m.Wherein berberine hydrochloride weight is 45～65% of berberine hydrochloride granule for masking flavor, and coating material includes:
(1) filmogen, be selected from Eudragit E100, Eudragit EPO, Eudragit L100, the hydroxypropyl emthylcellulose one or more, it can be dissolved in alcohol, water, dissolve in alcohol, water mixed solvent again, compound concentration is 10～20%, and consumption is 70～80% of a taste masking coating material weight; The effect and the advantage of filmogen are as follows: a. can be dissolved in gastro-intestinal Fluid, can discharge the efficacy of a drug faster in vivo after oral; B. it is low to be made into the coating solution viscosity, when the bag berberine hydrochloride granule, should not glue chain between particle; C. can form tough and tensile complete film, wear-resisting, light hides bitterness, is not absorbed by the body, nonirritant, with berberine hydrochloride compatibility reaction does not take place.
(2) plasticizer is selected from PEG6000, decanedioic acid dibutylester (DBS) and the triethyl citrate one or more, and its amount is 5～15% of taste masking coating material weight; The effect of plasticizer and select the foundation of this scope as follows: plasticizer is the small molecule material, when it joins in the high molecular polymer (filmogen), in will penetrating between macromolecular chain, reduce intermolecular or the intramolecularly active force, make the loose of high molecular network structure change, the plasticizer that adds this amount is easy to film forming, increases as consumption and then can cause the softening of material, causes sticking chain.
(3) antistatic additive is selected from magnesium stearate, Pulvis Talci and the micropowder silica gel one or more, and its amount is 5～15% of taste masking coating material weight; The effect of antiplastering aid and select the foundation of this scope as follows: in coating, add a certain amount of antiplastering aid to help the abundant fluidisation of berberine hydrochloride granule, to reduce between berberine hydrochloride granule sticking chain significant.But excessive when the amount of antiplastering aid, then can damage coating membrane.
Described taste masking coating material also includes:
(4) surfactant is selected from tween 80 or sodium lauryl sulphate or several, and its amount is 5～10% of taste masking coating material weight.The effect of surfactant and select the foundation of this scope: the permeability that can improve the clothing film.
(5) defoamer is selected from methyl-silicone oil, the polydimethylsiloxane one or more, and its amount is 2～5% of taste masking coating material weight; The effect of defoamer and select the foundation of this scope as follows: can make film smooth, smooth, the space is few, has complete compactness.
Described particulate granularity is 200～800 μ m.The easier formation suspension of the dosage form of the preparation of granules of this particle size range can not produce grittiness in mouth.
The preparation of berberine hydrochloride granule for masking flavor realizes by art for coating.
The berberine hydrochloride art for coating is as follows:
The first step places fluid bed with berberine hydrochloride, feed air-flow, borrow the air-flow that rises rapidly to make particle suspending roll when being in fluidized state up and down in space, coating chamber, solution input fluid bed with above-mentioned coating material also atomizes in addition, so that berberine hydrochloride surface adhesion one deck plasticity coating material, continue to feed hot-air and make it dry, as the method operation, until reaching the requirement of granule regulation.
Second step placed centrifugal examination fluid bed with above-mentioned coating berberine hydrochloride granule, rotate by centrifugal fluid bed turntable, produce very big centrifugal force, making the berberine hydrochloride that is contained in wherein be radial rolls to the locular wall direction, air-flow makes the material formation stream condition that moves upward, the gravity of berberine hydrochloride self overcomes air-flow again to be promoted, again fall on the rotating disk, like this, the atomizing coating material solution rotating direction of granule and coating chamber sidewall is consistent to spray into uniformly, as the method operation, till granule weightening finish 80～100%.Coating gained particle surface is smooth like this, and the space is few, the more complete densification of clothing film, and the coating time is short, and the yield height is convenient to suitability for industrialized production.
Berberine hydrochloride granule for masking flavor disclosed in this invention has been covered the bitterness of berberine hydrochloride fully, eliminated zest, berberine hydrochloride granule for masking flavor adds an amount of pharmaceutics usual excipients, can be made into the various peroral dosage forms that people are easy to accept, as dry suspension, dispersible tablet, chewable tablet and dried suspension etc.
Usual excipients comprises correctives (cyclamate, A Siba are sweet, xylitol, sorbitol), suspending agent (carbomer 971, polyvinylpyrrolidone k-90, the preferred carbomer of sodium carboxymethyl cellulose), filler (soluble starch, microcrystalline Cellulose, mannitol), disintegrating agent (carboxymethyl starch sodium, polyvinylpolypyrrolidone), fluidizer (silicon dioxide, polyethylene glycol 6000, magnesium stearate), coloring agent (citric acid, the preferred lemon yellow of beta-carotene) etc. in the taste masking berberine hydrochloride preparation.
Advantage of the present invention is: by with coating material berberine hydrochloride being carried out coating, covered the distinctive bitterness of berberine hydrochloride fully, improved the compliance of patient's medication; The use of coating material has also increased the dissolubility of berberine hydrochloride, helps drug effect and brings into play rapidly; Berberine hydrochloride granule for masking flavor can be used to prepare the peroral dosage form that multiple traditional handicraft can't prepare, especially at the special form (as dry suspension) of some specific crowd (as infant and swallow inconvenient old man), to make take medicine more safe and effective, reduce patient's medication misery, crucial meaning is arranged for patient that can not or should not oral conventional tablet.Preparation technology of the present invention is simple relatively simultaneously, is easy to suitability for industrialized production.
The invention will be further described below in conjunction with the specific embodiment, and do not limit the present invention in any way.All any this areas of doing according to the disclosure of invention be equal to replacement, all belong within protection scope of the present invention.
The specific embodiment
Embodiment 1: preparation taste masking berberine hydrochloride dry suspension
In order to prepare taste masking berberine hydrochloride dry suspension, begin by the berberine hydrochloride coated granule, its component is as follows:
| The compositions of coated granule | ||
| Active substance | Berberine hydrochloride | ????330g |
| Filmogen | ????Eudragit?E100 | ????143g |
| Plasticizer | ????PEG????6000 | ????27g |
| Fluidizer/antistatic additive | Micropowder silica gel | ????20g |
| Surfactant | Tween 80 | ????10g |
Prepare berberine hydrochloride granule for masking flavor in accordance with the following methods:
The first step is that coating amount Eudragit E100, PEG6000, magnesium stearate, tween 80 are joined in the ethanol (70%) of 1000ml, and with high-shear homogenate machine or the abundant homogenize of colloid mill 15 minutes, till forming homodisperse liquid.
Second step was by berberine hydrochloride is joined in the fluidized bed plant, spray velocity with 20g/min, 0.15Mpa hydrojet atomizing pressure, the inlet temperature of 35 ℃ and the 40 ℃ above-mentioned dispersion liquid of spraying, prepare coated granule with the spray of fluid bed top, 40 minutes internal spraying 50% coating dispersion liquids, dry 2 to 5 minutes, be to sieve on the sieve of 500 μ m the granule that obtains, then sized granules carried out coating once more with rotating fluidized bed at sieve aperture.
Rotary drum and 0.2Mpa spraying liquefaction pressure with 300rpm, nozzle by tangential direction is sprayed onto coating solution on the granule with the speed of 70g/min, the intake air temperature is 42 ℃, after all coating solution sprayed, on the low velocity rotary drum of 100rpm with the dry 8min of all coated granule, promptly get taste masking berberine granule, particle surface is smooth, the space is few, have complete compactness.
Coated granules contains 60.1% (weight) berberine hydrochloride.
Again the gained coated granule is formulated as the masked berberine hydrochloride dry suspension, specification is every bag of hydrochloric berberine 50mg, and its component is as follows:
| The dry suspension compositions | |
| Component | Amount (mg)/bag |
| Berberine hydrochloride granule for masking flavor (60% active ingredient) | ????83.4 |
| Xylitol | ????768 |
| Carbomer 971 | ????40 |
| Fructus Citri tangerinae flavor powdered flavor | ????1.5 |
| Micropowder silica gel | ????1.5 |
| Lemon yellow 60 | In right amount |
| Sweeting agent | In right amount |
| Microcrystalline Cellulose | ????116.6 |
| Sorbitol | ????489 |
| Amount to | ????1500 |
The dry suspension preparation method: berberine hydrochloride granule and adjuvant by the equivalent mixing method stirring and evenly mixing that progressively increases, are being operated in the clean room more than 1000 grades, and packing is to prevent contamination by micro.Spatial relative humidity should be less than 75%, to avoid the sample moisture absorption.Press under two appendix IO items of Chinese Pharmacopoeia (version in 2000) and check, check that the evaluation index method is as follows:
1, berberine hydrochloride suspensoid dissolution rate according to the present invention's preparation, the dissolution rate method: sample thief is according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), with 1000ml acetate buffer (ph=3.5) is solvent, rotating speed is 50/min, operation in accordance with the law, through 5,10,20,30, got solution 5ml in 45 minutes, filter, get subsequent filtrate 2ml and place the 25ml volumetric flask, add acetate buffer (ph=3.5) and be diluted to scale, shake up, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), wavelength place at 263nm measures trap, presses C
20H
18ClNO
42H
2Absorptance (the E of O
1cm 1%) be 724, calculate stripping quantity and see Table 1:
| Time min | ????5 | ????10 | ????20 | ????30 | ????45 |
| Dissolution % | ????40.2 | ????60.2 | ????83.6 | ????99.4 | ????102.2 |
2, the volume ratio inspection method is fallen:
According to (two appendix IO of Chinese Pharmacopoeia version in 2000), apparatus plug graduated cylinder is contained test sample 50ml, close plug, and firmly jolting is 1 minute, writes down the beginning height of suspended matter, leaves standstill 3 hours, writes down the final height of suspended matter then.Be calculated as follows: settling volume ratio=final height/beginning height, general oral suspensions (comprising suspensoid) settling volume ratio is not less than 0.90. and sees Table:
| The beginning height | ????50 | ????50 | ????50 |
| The final height of sedimentation | ????49 | ????49 | ????48 |
| The settling volume ratio | ????0.98 | ????0.98 | ????0.96 |
Embodiment 2:
Preparation taste masking berberine hydrochloride dispensing tablet
In order to prepare the taste masking berberine hydrochloride dispensing tablet, begin by the berberine hydrochloride dispersion liquid, its component is as follows
| The compositions of berberine hydrochloride dispersion liquid | ||
| Active substance | Berberine hydrochloride granule for masking flavor | ????200g |
| Filmogen | ????EudragitE100 | ????90g |
| ????EudragitL100 | ????50g | |
| Plasticizer | Triethyl citrate | ????20g |
| Antiplastering aid | Micropowder silica gel | ????20g |
| Defoamer | Silicone oil | ????9g |
Prepare berberine hydrochloride granule for masking flavor in accordance with the following methods:
The first step places EudragitE100, hydroxypropyl emthylcellulose 70% ethanol 1000ml, soak dissolving, add berberine hydrochloride again, the speed dispersed with stirring that water bath with thermostatic control with 50% is 18000 rev/mins, add 10% citric acid solution while stirring, adjust pH is about 3, and then add micropowder silica gel, methyl-silicone oil, be uniformly dispersed with high cutting homogenizer (or colloidal film), take out, with 800 rev/mins to below 10 ℃, add 20% sodium hydroxide solution and regulate pH value and show neutral, continue to stir to prevent precipitation.Obtain the berberine hydrochloride dispersion liquid thus.
Second step was by with above-mentioned berberine hydrochloride dispersion liquid bed spray, make its temperature remain on fluidized granulation under the condition between 20～35 ℃, with the berberine hydrochloride dispersion liquid of having sprayed of about 3 hours time, dry 10 minutes then, be to sieve on the sieve of 60 μ m the granule that obtains at sieve aperture, use the coating solution reuse fluid bed among the embodiment 1 to spray then, make berberine hydrochloride granule for masking flavor weightening finish 10%.
Again the gained taste masked particle is mixed with dispersible tablet, specification is every hydrochloric berberine 50mg, and its component is as follows:
| The compositions of dispersible tablet | |
| Component | Amount (mg/ sheet) |
| Taste masking berberine hydrochloride compositions (50% active ingredient) | ????100 |
| Microcrystalline Cellulose | ????100 |
| Cyclamate | ????10 |
| Polyvinylpolypyrrolidone | ????30 |
| Soluble starch | ????153 |
| Mannitol | ????194 |
| Micropowder PEG | ????7 |
| 10% 30 POVIDONE K 30 BP/USP, 3040% alcoholic solution | In right amount |
| Magnesium stearate | ????6 |
| Flavochrome | In right amount |
| Amount to | ????600mg |
The preparation method of dispersible tablet:
(1) by recipe quantity take by weighing polyvidone, pigment adds 75% dissolve with ethanol, it is standby to be mixed with the yellow alcoholic solution of 10% polyvidone.
(2) take by weighing berberine hydrochloride granule for masking flavor, microcrystalline Cellulose, cyclamate, soluble starch, carbomer 911,50% polyvinylpolypyrrolidone, flavochrome by recipe quantity and put mix homogeneously in the container, add lubricant and remaining disintegrating agent with 10% polyvidone yellow solution spray granulation, tabletting promptly.Press under two appendix IA items of Chinese Pharmacopoeia (version in 2000) and check, check that the evaluation index method is as follows:
1, berberine hydrochloride dispensing tablet dissolution rate according to the present invention's preparation, the dissolution rate method: sample thief is according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2000 C, second method), with 1000ml acetate buffer (ph=3.5) is solvent, rotating speed is 50/min, operation in accordance with the law, through 5,10,20,30, got solution 5ml in 45 minutes, filter, get subsequent filtrate 2ml and place the 25ml volumetric flask, add acetate buffer (ph=3.5) and be diluted to scale, shake up, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), wavelength place at 263nm measures trap, presses C
20H
18ClNO
42H
2Absorptance (the E of O
1cm 1%) be 724, calculate stripping quantity and see Table 1:
| Time min | ??5 | ??10 | ??20 | ??30 | ??45 |
| Dissolution % | ??30.2 | ??40.3 | ??81.4 | ??99.9 | ??100.2 |
2, disintegration time: in 20 ℃ of water, measure, should meet Chinese Pharmacopoeia version regulation in 2000 disintegration less than 3min in accordance with the law.
3, dispersed homogeneous degree: get 2 of this product and put into the 100ml distilled water and stir, it is disperseed fully, form uniform sticky suspension, and be the screen cloth of 710 μ m by the aperture.
Every measurement result:
| Dispersible tablet | Disintegration time | ????1.1min |
| Dispersed homogeneous degree | Whole screen clothes by 710 μ m | |
| Average sheet is heavy | ????600.3mg |
Embodiment 3:
Preparation taste masking berberine hydrochloride chewable tablet
In order to prepare taste masking berberine hydrochloride chewable tablet, begin by the berberine hydrochloride coated granule, its component is as follows:
| The compositions of coated granule | ||
| Active substance | Berberine hydrochloride | ????200g |
| Filmogen | Hydroxypropyl emthylcellulose 3mpa.s | ????20g |
| ????EudragitEPO | ????124g | |
| Sweeting agent | A Siba is sweet | ????10g |
| Antistatic additive | Magnesium stearate | ????20g |
| Defoamer | Polydimethylsiloxane | ????6g |
| Surfactant | Sodium lauryl sulphate | ????20g |
Prepare berberine hydrochloride granule for masking flavor in accordance with the following methods:
The first step is that coating amount hydroxypropyl emthylcellulose 3mpa.s, EudragitEPO, A Siba is sweet, micropowder silica gel, polydimethylsiloxane, sodium lauryl sulphate join in the 1000ml ethanol (50%), and with high-shear homogenate machine or the abundant homogenize of colloid mill 15 minutes, till forming homodisperse liquid.
Second step was by berberine hydrochloride is joined in the fluidized bed plant, spray velocity with 20g/min, 0.15Mpa hydrojet atomizing pressure, the inlet temperature of 35 ℃ and the 40 ℃ above-mentioned dispersion liquid of spraying, prepare coated granule with the spray of fluid bed top, 40 minutes internal spraying 50% coating dispersion liquids, dry 3 to 10 minutes, be to sieve on the sieve of 800 μ m the granule that obtains, then sized granules carried out coating once more with rotating fluidized bed at sieve aperture.
Rotary drum and 0.2Mpa spraying liquefaction pressure with 300rpm, nozzle by tangential direction is sprayed onto coating solution on the granule with the speed of 70g/min, the intake air temperature is 42 ℃, after all coating solution sprayed, on the low velocity rotary drum of 100rpm with the dry 8min of all coated granule, promptly get berberine hydrochloride granule for masking flavor, particle surface is smooth, the space is few, have complete compactness.
Coated granules contains 50.8% (weight) berberine hydrochloride.
Again the gained coated granule is formulated as the berberine hydrochloride chewable tablet, every hydrochloric berberine 50mg, its component is as follows:
| The compositions of chewable tablet | |
| Component | Amount (mg/ sheet) |
| Taste masking berberine hydrochloride compositions (50% active ingredient) | ????100 |
| Mannitol | ????417 |
| Microcrystalline Cellulose | ????150 |
| Comminution by gas stream spice | ????5 |
| The 10%PVP alcoholic solution | In right amount |
| Erythritol | ????100 |
| A Siba is sweet | ????10mg |
| Magnesium stearate | ????8 |
| Pigment | In right amount |
| Amount to | ????800mg |
With spray grain, 40 ℃ of dryings at the bottom of the usefulness fluid bed behind each material mix homogeneously, add magnesium stearate and mix 10min, obtain taste masking berberine hydrochloride chewable tablet with the rotary tablet machine tabletting, the heavy 808mg of average sheet, sheet hardness 3.8Kp, the fragility that detects by (Chinese Pharmacopoeia 2000 editions) two appendix IA methods is 1.1%.
Embodiment 4
Below through detection bodies listing acid hydrochloride salt berberine sheet and taste masked dosage form of the present invention.Beneficial effect of the present invention is described.
The dissolution rate method: sample thief is according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), with 1000ml acetate buffer (ph=3.5) is solvent, rotating speed is 50/min, operation in accordance with the law, got solution 5ml through 5,10,20,30,45 minutes, filter, get subsequent filtrate 2ml and place the 25ml volumetric flask, add acetate buffer (ph=3.5) and be diluted to scale, shake up, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure trap at the wavelength place of 263nm, press C
20H
18ClNO
42H
2Absorptance (the E of O
1cm 1%) be 724, calculate stripping quantity.
Taste masking berberine hydrochloride dosage form and listing berberine hydrochloride capsule testing result
| Detect index | Time | Dry suspension | Dispersible tablet | Chewable tablet | The listing tablet |
| Dissolution | ????5min | ????40.2％ | ????30.2％ | ????20.6％ | ????17.5％ |
| ????10min | ????60.2％ | ????40.3％ | ????50.6％ | ????30.2％ | |
| ????20min | ????86.3％ | ????81.4％ | ????80.4％ | ????45.6％ |
| ????30min | ????99.4％ | ????99.3％ | ????99.3％ | ????72.6％ | |
| ????45min | ????102.2％ | ????100.2％ | ????100.8％ | ????84.7％ |
Conclusion: obviously improve than the listing tablet by above-mentioned stripping result dosage form dissolution of the present invention as can be known, dissolubility height of the present invention is described, rapid-action.
Enforcement power 5
With the taste masking berberine hydrochloride preparation that makes in the enforcement power 1～3, to taste through 30 children, its bitterness is covered, and mouthfeel is significantly better than existing berberine hydrochloride ordinary preparation.
30 children, 6.6 years old mean age, wherein the boy is 14,16 of young girls.Test divides to be carried out in three weeks, all 30 children was divided into two groups at random at every turn, carried out taste test in set time weekly, and result of the test is as follows:
Show that by above test taste masking berberine hydrochloride preparation mouthfeel is good, covered the peculiar bitterness of the berberine hydrochloride ordinary preparation of present production fully, be easier to be accepted by child patient.
Claims (6)
1. berberine hydrochloride granule for masking flavor, it is characterized in that: this particulate granularity is 50～2000 μ m, form by taste masking coating material and the berberine hydrochloride that is wrapped in wherein, wherein the amount of berberine hydrochloride is 45～65% of a berberine hydrochloride granule for masking flavor gross weight, remaining is the taste masking coating material, includes:
(1) filmogen is selected from Eudragit E100, Eudragit EPO, Eudragit L100, the hydroxypropyl emthylcellulose one or more, and its amount is 70～80% of taste masking coating material gross weight;
(2) plasticizer is selected from PEG6000, dibutyl sebacate and the triethyl citrate one or more, and its amount is 5～15% of taste masking coating material gross weight;
(3) antistatic additive is selected from magnesium stearate, Pulvis Talci and the micropowder silica gel one or more, and its amount is 5～15% of taste masking coating material gross weight;
2. taste masking berberine salt granule according to claim 1 is characterized in that: described taste masking coating material also includes;
(4) surfactant is selected from tween 80 or sodium lauryl sulphate or several, and its amount is 5～10% of taste masking coating material gross weight;
(5) defoamer is selected from methyl-silicone oil, the polydimethylsiloxane one or more, and its amount is 2～5% of taste masking coating material gross weight.
3. berberine hydrochloride granule for masking flavor according to claim 1 and 2 is characterized in that: described particulate granularity is 200～800 μ m.
4. taste masking berberine hydrochloride preparation, it is characterized in that: said preparation contains claim 1 or 2 described berberine hydrochloride granule for masking flavor.
5. taste masking berberine hydrochloride preparation according to claim 4 is characterized in that: described preparation is a peroral dosage form.
6. taste masking berberine hydrochloride preparation according to claim 5, it is characterized in that: described peroral dosage form comprises dry suspension, dispersible tablet and chewable tablet.
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| CN102512377A (en) * | 2011-12-22 | 2012-06-27 | 杭州高成生物营养技术有限公司 | Tasteless quick-releasing berberine hydrochloride pellet |
| CN102716171A (en) * | 2012-06-28 | 2012-10-10 | 江西本草天工科技有限责任公司 | Compound common andrographis herb taste-masking particles and preparation method thereof |
| CN101502492B (en) * | 2009-03-13 | 2013-11-27 | 上海微丸医药开发有限公司 | Method for preparing clarithromycin granule without bitter taste |
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| US20190343957A1 (en) * | 2014-03-24 | 2019-11-14 | Kashiv Biosciences, Llc | Method Of Manufacturing Fine Particles Suitable For Orally Disintegrating Pharmaceutical Dosage Forms |
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| CN109464417A (en) * | 2018-12-19 | 2019-03-15 | 中国药科大学 | A kind of demethyleneberberinehydrochloride hydrochloride capsulae enterosolubilis and preparation method thereof |
| CN110638785A (en) * | 2019-09-29 | 2020-01-03 | 黄山中皇制药有限公司 | Andrographolide dry suspension |
| CN110638785B (en) * | 2019-09-29 | 2021-09-24 | 黄山中皇制药有限公司 | Andrographolide dry suspension |
| CN115444827A (en) * | 2021-06-08 | 2022-12-09 | 南京科默生物医药有限公司 | Pharmaceutical composition and preparation method thereof |
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