CN103156814A - Azithromycin enteric composition and preparation method - Google Patents
Azithromycin enteric composition and preparation method Download PDFInfo
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- CN103156814A CN103156814A CN2011104083387A CN201110408338A CN103156814A CN 103156814 A CN103156814 A CN 103156814A CN 2011104083387 A CN2011104083387 A CN 2011104083387A CN 201110408338 A CN201110408338 A CN 201110408338A CN 103156814 A CN103156814 A CN 103156814A
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Abstract
The invention discloses an azithromycin enteric composition capable of rapidly dispersing and releasing medicines in intestinal tracts and a preparation method for the same. The medicine composition is composed of the following raw materials: azithromycin, lactose, microcrystalline cellulose, sodium carboxymethyl starch, hydroxypropyl methylcellulose, lauryl sodium sulphate, polyvinylpyrrolidone, magnesium stearate and the like. The preparation method for azithromycin enteric tablets disclosed by the invention comprises the steps of treating the medicines and medicinal excipients and then tabletting, and performing enteric coating on tablet cores. The azithromycin enteric composition disclosed by the invention can be greatly protected in a gastric acid condition and thus effectively protecting the medicines from the breakage of gastric acid, and can achieve the characteristics of dispersible tablets in an intestinal juice condition (phosphate buffer having a pH value of 6.8) and thus rapidly releasing the medicines in intestinal tracts and increasing bioavailability.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of Azithromycin enteric composition and method of making the same that can rapid dispersion in intestinal discharges medicine.
Background technology
Azithromycin is a kind of fifteen-membered ring macrolide antibiotics that is derived by erythromycin, and nitrogenous 15 membered ring compounds of this class have stronger alkalescence, and many gram negative bacilli are had larger activity, and concentration is higher in tissue, and Half-life in vivo is long.Have common point with erythromycin on Antibacterial Mechanism, all be combined by ribosome 50S subunit in bacterial cell, hinder antibacterial and turn the peptide process, inhibition depends on the synthesizing of protein of RNA and reaches antibacterial action.But the change due to structure, azithromycin has antimicrobial spectrum widely than erythromycin, can suppress multiple gram positive coccus, mycoplasma, chlamydia and legionella pneumophilia, especially some important gram negative bacillis such as hemophilus influenza etc. are had good antibacterial activity, made up the Macrolide deficiency poor to the haemophilus effect.Be mainly used in the transmissible disease due to respiratory tract, skin soft-tissue infection and the chlamydia due to sensitive organism.Present azithromycin is sure to occupy medicine tap in macrolide with the advantage of himself uniqueness.
Azithromycin listing dosage form is more at present, and conventional tablet, dispersible tablet, capsule, granule, dry suspension, enteric coatel tablets, injection etc. are arranged.In the recent period a large amount of research data documents show that azithromycin is unstable under gastric acid environment, 30min degraded 68% in the 0.1mol/L hydrochloric acid solution, cause bioavailability on the low side, and this class macrolide antibiotics ubiquity gastrointestinal side reaction, the discomfort such as easily cause that the patient vomits, main cause is that it is to the stimulation of stomach.Be to reduce medicine to the stimulation of stomach, and guarantee that azithromycin avoids the destruction of gastric acid, the enteric coated preparation of this medicine has become development trend.
At present the patent application of this medicament enteric-coated formulation aspect is more, domestic had Azithromycin enteric sheet and enteric coated capsule to go on the market, but such enteric coated preparation discharged slow, usually there is the interior bioavailability of body lower, relatively poor in colon position absorption, onset is the deficiency of aspect such as slowly, the invention of relevant Azithromycin enteric casing preparation patent, but still may cause bioavailability on the low side.
Patent CN1602888A (open day on April 6th, 2005) discloses Azithromycin enteric casing preparation and preparation method thereof, the method with soft just after drying the granule of conventional preparation as starting material, enteric coatedly after tabletting make enteric coatel tablets for Opadry-93018359, or with initial particles filled in enteric capsule shell, because being subjected to the impact of Opadry material and enteric capsule shell, the method may cause bioavailability too low.Patent 1569021A discloses a kind of Azithromycin enteric casing preparation and preparation method thereof; it adopts conventional material and preparation method carry out the granulation of core material or make micropill; this method can cause its release slow; particularly make micropill and make again later on enteric coated preparation; can increase the drug release process of micropill, affect drug absorption.It is untimely that the selection of its enteric material can cause medicine to arrive intestinal release later on, may cause bioavailability too low.Patent CN101991544 discloses a kind of Azithromycin enteric dry suspension and preparation method thereof; this patent is that azithromycin granule is put in coating granulator; granule is carried out carrying out enteric coating after isolation coat again, and the enteric coated particles of gained adds the mixing such as a large amount of correctivess and suspending agent and get final product.Although might improve drug release rate; accelerate drug effect and improve bioavailability; but because of the specific surface area of this technique drug particles too large; complicated process of preparation; need relatively large use coating material, and coatings protect is incomplete, has bitterness; need add a large amount of correctivess and suspending agent, have the shortcoming that medicine can not be effectively protected and dosage is larger in gastric acid.
Therefore, still need at present a kind of new Azithromycin enteric casing preparation, neither can produce stomach stimulates, the advantageous feature that can possess again dispersible tablet namely in intestinal disintegrate rapidly, absorb fast, bioavailability is high.
Summary of the invention
The object of the present invention is to provide a kind of Azithromycin enteric compositions, another purpose of the present invention is to provide a kind of preparation method of Azithromycin enteric compositions.
The present invention seeks to be achieved through the following technical solutions
The raw material of pharmaceutical composition of the present invention consists of:
Azithromycin 100 weight portion starch 0～50 weight portions
Lactose 0～30 weight portion microcrystalline Cellulose 0～70 weight portion
Carboxymethylstach sodium 0～20 weight portion cross-linking sodium carboxymethyl cellulose 0～30 weight portion
Polyvinylpolypyrrolidone 0～30 weight portion hypromellose 0～30 weight portion
Sodium lauryl sulphate 0～3 weight account polyethylene pyrrole alkane ketone 0～10 weight portion
Micropowder silica gel 0～50 weight portion magnesium stearate 0.5～5 weight portion.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 10～30 weight portion microcrystalline Cellulose 40～60 weight portions
Carboxymethylstach sodium 3～15 weight portion cross-linking sodium carboxymethyl cellulose 5～20 weight portions
Hypromellose 10～30 weight portion sodium lauryl sulphate 0.5～2.5 weight portions
The polyethylene pyrrole alkane ketone 4～10 weight portion magnesium stearate 0.5～3 weight portions.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 18～22 weight portions
Microcrystalline Cellulose 45～55 weight portion carboxymethylstach sodium 8～10 weight portions
Hypromellose 25～30 weight portion sodium lauryl sulphate 1～2 weight portions
The polyethylene pyrrole alkane ketone 6～8 weight portion magnesium stearate 1～2 weight portions.
The preferred weight proportioning of above-mentioned raw materials is as follows:
Azithromycin 100 weight portion lactose 20 weight portions
Microcrystalline Cellulose 50 weight portion carboxymethylstach sodium 9 weight portions
Hypromellose 27.5 weight portion sodium lauryl sulphate 1.5 weight portions
The polyethylene pyrrole alkane ketone 7 weight portion magnesium stearate 1.5 weight portions.
Get the combinations thereof raw material, add conventional adjuvant, according to common process, make tablet.
Pharmaceutical composition of the present invention adds the material of following weight portion to make enteric coatel tablets:
Enteric material contains thing 10 weight portions admittedly, antiplastering aid 2～10 weight portions, plasticizer 1～7 weight portion.
The preferred weight proportioning is as follows: enteric material contains thing 10 weight portions admittedly, antiplastering aid 6 weight portions, and plasticizer 4 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 3 weight portions, plasticizer 6 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 9 weight portions, plasticizer 2 weight portions.
It is methacrylic acid and ethyl acrylate copolymer (especially strange L30D-55 or title Eudragit L100-55) or methacrylic acid and methylmethacrylate copolymer (especially strange L100) or two kinds of mixture that described enteric material contains thing admittedly.
Described antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel.
Described plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
The concrete preparation technology of medicinal composition tablets of the present invention is as follows:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 80～120 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 16～24 mesh sieves are granulated, and granule is put 50～70 ℃ of drying 2～4h, and 18～24 mesh sieves are granulated, and add 0～12 weight portion micropowder silica gel, 0～5 weight portion hypromellose and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 10%～20%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 3%～10%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 2%～12%.
The preferred preparation technology of medicinal composition tablets of the present invention is as follows:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 100 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 20 mesh sieves are granulated, and granule is put 60 ℃ of dry 3h, and 20 mesh sieves are granulated, and add 0～6 weight portion micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 15%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 6%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 5%.
Azithromycin enteric compositions of the present invention; can well be protected under the gastric acid condition, effectively protect medicine to avoid the destruction of gastric acid, and (phosphate buffer PH6.8) can reach the characteristics of dispersible tablet under the intestinal juice condition; rapid delivery of pharmaceuticals in intestinal improves bioavailability.With the Azithromycin enteric tablet that the inventive method makes, taking convenience is covered bad bitterness, increases medicine stability, can effectively protect medicine not to be subjected to stomach acids destroy in the hydrochloric acid solution of 0.1mol/L, can rapid delivery of pharmaceuticals in simulated intestinal fluid.
Following experimental example and embodiment are used for further illustrating but being not limited to the present invention.
Experimental example 1: release experiment in acid
Measure with reference to 2010 editions two ones of Chinese Pharmacopoeias (appendix XC the second method), take the hydrochloric acid solution 900ml of 0.1mol/L as dissolution medium, temperature (37 ± 0.5 ℃), rotating speed 50r/min.6 of medicinal composition tablets of the present invention getting embodiment 11 preparation are put in stripping rotor respectively and are measured, draw solution 10ml after 2h, getting subsequent filtrate adopts high performance liquid chromatography to carry out the assay of azithromycin, another precision takes the azithromycin reference substance, the solution of making 0.2mg/ml with mobile phase dilution is product liquid in contrast, measure with method, calculate release, press in the acid of Chinese Pharmacopoeia enteric coated preparation that release stipulates should be less than 10%.Its chromatographic condition is: be filler with octadecylsilane chemically bonded silica; (get the 0.05mol/L dipotassium hydrogen phosphate solution, the phosphoric acid solution with 20% is regulated pH value to 8.2)-acetonitrile (45: 55) is mobile phase with phosphate buffer; The detection wavelength is 210nm; Flow velocity: 1.0ml/min; Sample size: 20 μ l; Measurement result is: azithromycin of the present invention release after 2h in acid is 2.1%.
Experimental example 2: the release experiment in artificial enteric liquid
A, the release medium in release experiment in acid (experimental example 1) is changed into simulated intestinal fluid (phosphate buffer PH6.8), other experimental techniques remain unchanged, and investigate and contrast the release profiles of other Azithromycin enteric sheets in simulated intestinal fluid.Experimental result is as follows:
B, the release medium in release experiment in acid is changed into phosphate buffer PH7.8～8.0, and (get dipotassium hydrogen phosphate 5.59g and potassium dihydrogen phosphate 0.41g, 1000ml is made in the dilution that is dissolved in water, and get final product.), other experimental techniques remain unchanged, and investigate and contrast the release profiles of other Azithromycin enteric sheets in simulated intestinal fluid.Experimental result is as follows:
Experimental example 3: finely dispersed test in simulated intestinal fluid
Assay method with reference to the Chinese Pharmacopoeia dispersed homogeneous degree, get 6 of the medicinal composition tablets of the present invention of embodiment 11 preparation, put in the 250ml beaker, add simulated intestinal fluid (phosphate buffer PH6.8) 100ml or phosphate buffer (PH7.8～8.0) 100ml of 15～25 ℃, jolt 3min, investigate whether all disintegrate and pass through sieve No. two, and compare with commercially available enteric coatel tablets and dispersible tablet.Experimental result is as follows:
Illustrate that azithromycin of the present invention can reach the requirement of dispersible tablet under the condition of simulated intestinal fluid (phosphate buffer PH6.8) and phosphate buffer (PH7.8～8.0), than other enteric coatel tablets more can disperse, fast release thing.
Following embodiment all can realize the described effect of above-mentioned experimental example.
Embodiment 1:
Core formulation and preparation:
Azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium are crossed respectively 100 mesh sieves, mix homogeneously; Polyvidone is made 5% solution with 50% ethanol; After the soft ability of 5%PVP alcoholic solution system, 18～24 mesh sieves are granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add the magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material, antiplastering aid and plasticizer, add water and stir evenly, with the abundant homogenize 20min of high speed shear refiner, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15.9%, get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 2:
Core formulation and preparation:
Azithromycin, micropowder silica gel, microcrystalline Cellulose, carboxymethylstach sodium, polyvidone are crossed respectively 100 mesh sieves, mix homogeneously; After the 50% soft ability of alcoholic solution system, 18～24 mesh sieves are granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add the magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get in enteric material solution 500g dissolving, add triethyl citrate, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 3:
Core formulation and preparation:
100 mesh sieves are crossed respectively in azithromycin, starch, microcrystalline Cellulose, micropowder silica gel, mix homogeneously (in add micropowder silica gel 140g); After sodium lauryl sulphate was made 0.5% solution and made soft ability with it with 50% ethanol, 18～24 mesh sieves were granulated, and granule is put 60 ℃ of drying 2～4h, and 18～24 mesh sieve granulate add micropowder silica gel (60g) and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get in enteric material solution 500g dissolving, add triethyl citrate, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 2%.
Embodiment 4:
Core formulation and preparation:
Azithromycin, starch, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 18%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 5:
Core formulation and preparation:
Azithromycin, starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 6:
Core formulation and preparation:
Azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add the SA dibutyl ester, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 16%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 7%.
Embodiment 7:
Core formulation and preparation:
100 mesh sieves, mix homogeneously are crossed respectively in azithromycin, starch, carboxymethylstach sodium, sodium lauryl sulphate, micropowder silica gel; The soft ability of povidone solution system of 50% ethanol preparation 5%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g water, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 16%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 6%.
Embodiment 8:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g95% ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly.Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 9:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material, antiplastering aid and plasticizer, add water and stir evenly, with the abundant homogenize 20min of high speed shear refiner, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15.9%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 10:
Core formulation and preparation:
Get azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose and cross respectively 100 mesh sieves, mix homogeneously; The soft ability of sodium dodecyl sulfate solution system of 50% ethanol preparation 0.75%, it is soft that granule is put 60 ℃ of drying 2～4h just with 18～24 mesh sieves granulations, and 18～24 mesh sieve granulate add micropowder silica gel, polyvinylpolypyrrolidone and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in the 500g solvent, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 10%.
Embodiment 11:
Core formulation and preparation:
Get azithromycin, lactose, microcrystalline Cellulose, carboxymethylstach sodium, hypromellose and cross respectively 100 mesh sieves, mix homogeneously; Get recipe quantity polyethylene pyrrole alkane ketone and sodium lauryl sulphate be added in 50% alcoholic solution of 140ml as the soft ability of binding agent system, softly just granulate with 20 mesh sieves, granule is put 60 ℃ of dry 3h, 20 mesh sieve granulate add the magnesium stearate mixing, tabletting namely gets label.
Enteric coating:
Get enteric material and put in the 500g solvent, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min; Two liquid are mixed, fully stir evenly; Be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 15%; Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 12:
Core formulation and preparation:
Get azithromycin, starch, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone and cross respectively 100 mesh sieves, mix homogeneously; The 50% soft ability of alcoholic solution system, it is soft that granule is put 65 ℃ of dry 4h just with 18 mesh sieves granulations, and 18 mesh sieve granulate add micropowder silica gel, hypromellose and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g95% ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition Pulvis Talci is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Embodiment 13:
Core formulation and preparation:
Azithromycin, starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate are crossed respectively 100 mesh sieves, mix homogeneously; The soft ability of povidone solution system of 50% alcoholic solution preparation 5%, it is soft that granule is put 55 ℃ of dry 2h just with 24 mesh sieves granulations, and 24 mesh sieve granulate add micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label.
Enteric coating:
Get enteric material and put in 500g ethanol, with the abundant homogenize 10min of high speed shear refiner, add triethyl citrate, continue to shear 20min, in addition magnesium stearate is poured in remaining solvent, shear 10min.Two liquid are mixed, fully stir evenly, be mixed with the coating solution that contains enteric material (polymer contains thing admittedly) 6%.Get label and set high effect and carry out coating in coating pan, controlling the coating weightening finish is 5%.
Claims (11)
1. Azithromycin enteric compositions is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion starch 0～50 weight portions
Lactose 0～30 weight portion microcrystalline Cellulose 0～70 weight portion
Carboxymethylstach sodium 0～20 weight portion cross-linking sodium carboxymethyl cellulose 0～30 weight portion
Polyvinylpolypyrrolidone 0～30 weight portion hypromellose 0～30 weight portion
Sodium lauryl sulphate 0～3 weight account polyethylene pyrrole alkane ketone 0～10 weight portion
Micropowder silica gel 0～50 weight portion magnesium stearate 0.5～5 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 10～30 weight portion microcrystalline Cellulose 40～60 weight portions
Carboxymethylstach sodium 3～15 weight portion cross-linking sodium carboxymethyl cellulose 5～20 weight portions
Hypromellose 10～30 weight portion sodium lauryl sulphate 0.5～2.5 weight portions
The polyethylene pyrrole alkane ketone 4～10 weight portion magnesium stearate 0.5～3 weight portions.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 18～22 weight portions
Microcrystalline Cellulose 45～55 weight portion carboxymethylstach sodium 8～10 weight portions
Hypromellose 25～30 weight portion sodium lauryl sulphate 1～2 weight portions
The polyethylene pyrrole alkane ketone 6～8 weight portion magnesium stearate 1～2 weight portions.
4. pharmaceutical composition as claimed in claim 3 is characterized in that the raw material of said composition consists of:
Azithromycin 100 weight portion lactose 20 weight portions
Microcrystalline Cellulose 50 weight portion carboxymethylstach sodium 9 weight portions
Hypromellose 27.5 weight portion sodium lauryl sulphate 1.5 weight portions
The polyethylene pyrrole alkane ketone 7 weight portion magnesium stearate 1.5 weight portions.
5. as claim 1,2,3 or 4 described pharmaceutical compositions, it is characterized in that said composition adds conventional adjuvant, makes tablet according to common process.
6. as claim 1,2,3 or 4 described pharmaceutical compositions, it is characterized in that this pharmaceutical composition also adds enteric material admittedly to contain thing 10 weight portions, antiplastering aid 2～10 weight portions, plasticizer 1～7 weight portion.
7. pharmaceutical composition as claimed in claim 6, it is characterized in that this pharmaceutical composition also adds enteric material admittedly to contain thing 10 weight portions, antiplastering aid 6 weight portions, plasticizer 4 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 3 weight portions, plasticizer 6 weight portions or enteric material contain thing 10 weight portions admittedly, antiplastering aid 9 weight portions, plasticizer 2 weight portions.
8. pharmaceutical composition as claimed in claim 6, is characterized in that it is methacrylic acid and ethyl acrylate copolymer or methacrylic acid and methylmethacrylate copolymer or two kinds of mixture that described enteric material contains thing admittedly; Antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel; Plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
9. pharmaceutical composition as claimed in claim 7, is characterized in that it is methacrylic acid and ethyl acrylate copolymer or methacrylic acid and methylmethacrylate copolymer or two kinds of mixture that described enteric material contains thing admittedly; Antiplastering aid is one or more in Pulvis Talci, magnesium stearate or micropowder silica gel; Plasticizer is one or more in triethyl citrate, SA dibutyl ester, propylene glycol.
10. as the preparation method of claim 7,8 or 9 described medicinal composition tablets, it is characterized in that the method is:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 80～120 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 16～24 mesh sieves are granulated, and granule is put 50～70 ℃ of drying 2～4h, and 18～24 mesh sieves are granulated, and add 0～12 weight portion micropowder silica gel, 0～5 weight portion hypromellose and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 10%～20%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 3%～10%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 2%～12%.
11. the preparation method of medicinal composition tablets as claimed in claim 10 is characterized in that the method is:
A. the making step of label: a. gets azithromycin, starch, and lactose, microcrystalline Cellulose, carboxymethylstach sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hypromellose, 100 mesh sieves, mix homogeneously are crossed respectively in micropowder silica gel; B. get the polyethylene pyrrole alkane ketone join in the solution of 50% ethanol, make contain the polyethylene pyrrole alkane ketone be 5% concentration, and add the sodium lauryl sulphate dissolving, as binding agent; C. binding agent is used for the soft ability of a system, 20 mesh sieves are granulated, and granule is put 60 ℃ of dry 3h, and 20 mesh sieves are granulated, and add 0～6 weight portion micropowder silica gel and magnesium stearate mixing, and tabletting namely gets label;
B. the making step of enteric coating: a. gets enteric material, antiplastering aid and plasticizer, adding water stirs evenly, be mixed with the coating solution that contains enteric material (admittedly containing thing) 15%, or add alcoholic solution and be mixed with the suspendible coating solution that contains enteric material (admittedly containing thing) 6%; B. get label and set high effect and carry out coating in coating pan, the coating weightening finish is 5%.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
| CN107582538A (en) * | 2017-06-01 | 2018-01-16 | 合肥远志医药科技开发有限公司 | Azithromycin capsule and preparation method thereof |
| CN110882228A (en) * | 2019-11-29 | 2020-03-17 | 南京禾瀚医药科技有限公司 | Epiputidine enteric-coated preparation |
| CN111228233A (en) * | 2020-03-11 | 2020-06-05 | 正大青春宝药业有限公司 | Coating composition for preparing perhexiline enteric-coated tablets and application thereof |
| CN112656774A (en) * | 2020-12-26 | 2021-04-16 | 海南葫芦娃药业集团股份有限公司 | Azithromycin enteric capsule and preparation method thereof |
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| CN1569021A (en) * | 2004-04-23 | 2005-01-26 | 石家庄制药集团欧意药业有限公司 | Enteric-coated azithromycin preparation and its preparing process |
| CN1602888A (en) * | 2004-07-30 | 2005-04-06 | 浙江大德药业集团有限公司 | Azithromycin enteric casing preparation and its preparing process |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1569021A (en) * | 2004-04-23 | 2005-01-26 | 石家庄制药集团欧意药业有限公司 | Enteric-coated azithromycin preparation and its preparing process |
| CN1602888A (en) * | 2004-07-30 | 2005-04-06 | 浙江大德药业集团有限公司 | Azithromycin enteric casing preparation and its preparing process |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107582538A (en) * | 2017-06-01 | 2018-01-16 | 合肥远志医药科技开发有限公司 | Azithromycin capsule and preparation method thereof |
| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
| CN110882228A (en) * | 2019-11-29 | 2020-03-17 | 南京禾瀚医药科技有限公司 | Epiputidine enteric-coated preparation |
| CN111228233A (en) * | 2020-03-11 | 2020-06-05 | 正大青春宝药业有限公司 | Coating composition for preparing perhexiline enteric-coated tablets and application thereof |
| CN112656774A (en) * | 2020-12-26 | 2021-04-16 | 海南葫芦娃药业集团股份有限公司 | Azithromycin enteric capsule and preparation method thereof |
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| CN103156814B (en) | 2015-11-25 |
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