CN101269085A - Oral preparation containing azithromycin, preparation method and application thereof - Google Patents
Oral preparation containing azithromycin, preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a buccal tablet containing Azithromycin, the preparation method and the use, and aims to provide a buccal tablet with Azithromycin adopted as the medicinal ingredient. The buccal tablet can be dissolved among the salvia in the oral cavity and enter the oral cavity, the pharynx and pharyngeal tonsils to play the role of resisting bacteria. The buccal tablet adopts Azithromycin as the medicinal ingredient and can be made into various pharmaceutical formulations, such as buccal tablets, candies, dropping pills and so on. The buccal tablet containing Azithromycin has the characteristics of fast effect, excellent curative effect and convenient drug delivery, can directly improve the concentration of antibiotic drugs at the pathological part and enhance the antibacterial capacity of the pathological part, and is more suitable for majorities of patients.
Description
Technical field
The present invention relates to a kind of medicine and its production and use, particularly contains buccal lozenge of azithromycin and its production and use.
Background technology
Pharyngitis is the modal disease of puzzlement modern life, is pharyngeal mucous membrane, submucous tissue and adenoid diffuse inflammation, often is the part of upper respiratory tract infection.Be divided into acute and chronic two kinds clinically.Acute pharyngitis is many in autumn and winter and morbidity at the end of winter and the beginning of spring.Pathological changes ordinary wave and whole pharyngeal cavity also can limit to a place.Can cause by virus, antibacterial and physical chemical factor and high temperature, dust, fumagine, irritative gas etc.Bacterial infection is based on gram-positive coccis such as streptococcus, staphylococcus and Diplococcus pneumoniaes.Wherein serious with A group group B streptococcus causer, antibacterial or toxin enter blood, can cause the purulent lesion of organ at a distance, are called acute septic pharyngitis.Treat with oral or injection antibiotics control infection.
The chronic pharyngitis course of disease is very long, and the symptom stubbornness is often by due to the local infection or general pathological changes secondary, with chronic pathological changes repeatedly acute attack be its characteristics, in many cases, acute attack is to be caused by bacterial infection, therefore, suitable antibacterial therapy helps to control acute symptom.
Acute tonsillitis is a kind of non-specific acute inflammation of very common palatine tonsil, often with to a certain degree pharyngeal mucous membrane and swallow adenoid acute inflammation.Main pathogenic bacterium are streptococcus, staphylococcus, Diplococcus pneumoniae.Adenovirus also can cause primary disease.Antibacterial and virus mixed infection are quite a few to be seen.Antibacterial may be extraneous the intrusion, also may be the antibacterial that is hidden in the tonsillar crypts, when Abwehrkraft des Koepers because of cold, humidity, overworked, have a delicate constitution, tobacco and wine are excessive, when factors such as harmful gas stimulation reduce suddenly, due to bacterial reproduction is strengthened.Acute tonsillitis is acute attack repeatedly on chronic tonsil basis often.Clinical manifestation aversion to cold, hyperpyrexia, pharyngalgia, aggravation etc. when swallowing can the concurrent rheumatic fever relevant with hemolytic streptococcal infection, multiple general diseases such as acute glome-rulonephritis, myocarditis, arthritis.Treatment adopts pain relieving to bring down a fever, oral or injection antibiotics control infection.
The oral cavity infection disease mainly comprises dental disease, periodontal and the disease of cari oris mucosa, as dental caries, pulpitis, periapical periodontitis, periodontitis, recurrent aphtha, oral ulcer, oral leukoplakia, monilial stomatitis, pericoronitis, necrotic stomatitis, thrush, gingivitis, membranous stomatitis, periodontal disease, herpetic stomatitis etc.Antibacterial is the important paathogenic factor that causes the oral cavity infection disease.Intraoral have a large amount of Gram-positives and a gram negative bacteria, and its value volume and range of product all occupies first of the whole body.According to the study, contain antibacterial in every milliliter of saliva and reach 1.5 hundred million.Under certain conditions, incorrect etc. when food debris accumulation, crowded dentition, method for brushing teeth, form dental plaque, tartar, when the kind of antibacterial changes, the amount of pathogenic bacterium increases or passive protective physical fitness descends, cause the generation of oral cavity infection disease.Therefore, oral cavity infection disease is caused by the various bacteria synergism.The patient often has symptoms such as toothache, gingival hemorrhage, redness, odontoseisis displacement, halitosis.Swelling and aching of gum, pyorrhea also can be used as infection focus, cause such as systemic diseases such as arthritis, the heart, cerebrovascular disease.
Treat pharyngitis, tonsillitis and oral cavity infection that bacterial infection causes, often select the antibiotics of resisting gram-positive bacteria for use, the antibiotics of the anti-gram negative bacteria of part also has therapeutical effect.Azithromycin is 15 yuan of ring macrolide antibiotics.Mechanism of action is identical with erythromycin, mainly combines with the 50S subunit of bacterial ribosome, and the albumen that inhibition depends on RNA synthesizes.In vitro tests proof azithromycin has antibacterial action to multiple common pathogen clinically, comprising: gram positive aerobic bacteria: staphylococcus aureus, A group β Hemolytic streptococcus, pneumonia (chain) coccus, Hemolytic streptococcus and other streptococcus, diphtheria (bar-shaped) bacillus.This product comprises that for the gram-positive bacteria of anti-erythromycin the multiple aureus strains of streptococcus faecalis (enterococcus) and methicillin-resistant presents cross resistance.Gram negative aerobic bacteria: hemophilus influenza, haemophilus parainfluenzae, mucositis mora bacterium, acinetobacter, yersinia's genus, legionella pneumophilia, bordetella pertussis, parapertussis bacillus, Shigella, Pasteurella, vibrio cholera, secondary Bacillus hemolyticus, class will are congratulated the pyrrole Plesiomonas.Be used for sensitive organism infectious disease such as acute pharyngitis, acute tonsillitis clinically.The preparation of having succeeded in developing of this medicine has tablet, capsule, injection etc., all adopts the oral whole body administration that waits.In view of oral absorption such as tablet and capsule slower, by the whole body distribution medicine is diluted in blood after entering blood, make medicine lower, and it is also longer to reach time of effective blood drug concentration at diseased region, influences its effective antibacterial efficacy at the blood drug level of diseased region.Therefore, the development buccal lozenge is by the oral cavity buccal, directly act on diseased region with high concentration medicine, be used for pharyngitis, pharyngoamygdalitis and oral cavity infection treatment of diseases, can overcome above-mentioned shortcoming, for effective treatment of throat oral cavity infection disease provides strong treatment means.
Summary of the invention
The purpose of this invention is to provide a kind of is the buccal lozenge and its production and use of ingredient with the azithromycin, the medicine through port is contained in the intraoral saliva and dissolves, enter around the oral cavity, pharyngeal and pharyngeal tonsil position, bring into play its antibacterial action, the clinical pharyngitis that is used for the treatment of, pharyngoamygdalitis and oral cavity infection disease, particularly by prolonging preparation in intraoral melting time, it is the disintegration of preparation, prolong the action time of medicine and local lesion, and then improved the treatment pharyngitis, the drug quality of pharyngoamygdalitis and oral cavity infection disease medicament.
For achieving the above object, the present invention has adopted following technical scheme.
The buccal lozenge that contains azithromycin of the present invention is made up of ingredient that comprises azithromycin and salt derivative thereof and substrate, its Chinese medicine: substrate=1: 0.5-1: 30.0, through port intracavity buccal administration clinically is characterized in that the application of described azithromycin buccal lozenge in treatment pharyngitis, pharyngoamygdalitis and oral cavity infection disease.Select 10-100 minute the disintegration of described azithromycin buccal lozenge, preferred 15-60 minute, more preferably 20-60, preferred 20-40 minute especially, by prolonging preparation in intraoral melting time, and then improve medicine to pharyngitis, pharyngoamygdalitis and oral cavity infection treatment of diseases effect, improve drug quality.
In the comfort level that described drug quality comprises side reaction and other discomfort brought to patient in the comfort level, drug use process of medication effect, drug use, medicine stores and carry, the characteristics such as complexity of drug manufacture one or multinomial.Described raising drug quality comprises the therapeutic effect that strengthens medicine, reduce and causedly in the drug use process do not accommodate misery, conveniently use, be easy to store and carry, improve safety that medicine uses, simplify production technology, reduce in the characteristics such as toxic and side effects of medicine one or multinomial, for example compare with injection, buccal lozenge has that production technology is simple, storage and convenient drug administration, can avoid fully injecting to what patient brought and do not accommodate the unsafe factor that misery and injection bring to patient.
Wherein, selected azithromycin is chemical compound and its esters (example hydrochloric acid salt, sulfate, Lactobionate, maleate, aspartate, citrate, phosphate, the fumarate etc.) derivant with following feature.
Chinese: azithromycin
English by name: Azithromycin
Formal name used at school is: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-and 13-[(2,6-dideoxy-3-C-methyl-3-0-methyl-a-L-nuclear-own pyrans glycosyl) oxygen]-2-ethyl-3,4, the 10-trihydroxy
-3,5,6,8,10,12,14-seven methyl isophthalic acid 1-[[3,4,6-three deoxidations-3-(dimethylamino)-β-D-wood-own pyrans glycosyl] oxygen]-1-oxa--6-azacyclo-pentadecane-15 ketone
Molecular formula: C
38H
72N
2O
12
Molecular weight: 749.00
Wherein said substrate is the preparation adjuvant that is grouped into by one or more one-tenth, comprises diluent (filler), binding agent, disintegrating agent, lubricant, fluidizer, slow releasing agent, coloring agent, correctives, spice etc.
Described preparation type includes but not limited to buccal tablet, drop pill, confection.As a kind of preparation type commonly used, buccal lozenge is meant and is contained in the oral cavity, the drug slow dissolving produces the pharmaceutical preparation of persistent local action, the main local therapeutic effects that rises, detect the whole disintegrates of planted agent in 30 minutes according to version Pharmacopoeia of People's Republic of China in 2005 detection method second disintegration.But the disintegration of present existing buccal lozenge is all below 10 minutes, as GUILIN XIGUA SHUANG buccal tablet, FUFANG CAOSHANHU HANPIAN, ribavirin buccal tablet, gluconic acid calcium tablet, ammonium iodide buccal tablet, JINSANGZIHOUBAO buccal tablet etc.Disintegration, the too fast medicine that then shows was short in partial action time, will obviously influence the topical therapeutic effect of medicine.The inventor is surprised to find by azithromycin being made buccal lozenge of the present invention by designing different pharmaceutical preparation technologies, remained on more than 10 minutes the disintegration of buccal lozenge, preferred 10-100 minute, dissolution insoluble or the insoluble drug composition reached more than 80% when making complete disintegrate simultaneously.For the preferred 20-60 minute disintegration of buccal lozenge for the purpose of the taking convenience, significant prolongation the action time of medicine and local lesion, thereby improved the topical therapeutic effect of medicine.
In addition, buccal lozenge is after containing of intraoral disintegration, and ingredient wherein should mainly be present in dissolved state just can bring into play its due therapeutical effect in the saliva.Azithromycin comprises prototype compound and salt derivative two classes; prototype compound almost insoluble in water wherein; do not carry out hydrotropy as preparation process and handle the then medicine purpose that very difficult realization mainly exists with dissolved state in saliva; therefore; the present invention utilizes surfactant polyethylene; polyoxyethylene stearate 40 esters; beta cyclodextrin; poloxamer; carboxymethyl starch sodium; substrate such as stearic acid and medicine material are made solid dispersion or sucrose; maltose; dextrinose; the dextrinose oligosaccharide; panose; cottonseed sugar; stachyose; oligofructose; glucose; fructose; lactose; inulin; protein sugar; stevioside; xylitol; maltose alcohol; sorbitol; gelatinized corn starch; syrup; Icing Sugar such as maltose and medicine material are made solid dispersion; make medicine be molecule; colloid or microcrystalline state are scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine had wetting action; can make medicine molten microgranule or the solution of loosing into rapidly; thereby make the dissolving of medicine and absorb quickening; thereby improved bioavailability, reached the purpose that significantly improves medicine topical therapeutic effect.
The present invention relates to contain the drop pill of following composition:
Described drop pill is made up of ingredient that includes azithromycin and substrate, adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine with suitable speed, splash in 40 →-15 ℃ the condensing agent liquid paraffin, methyl-silicone oil, vegetable oil any one or a few, drying forms, and its mesostroma is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more one-tenth in polyoxyethylene stearate 40 esters, beta cyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers and the medicinal slow release agent are grouped into.
The present invention relates to contain the buccal tablet of following composition:
Described buccal tablet is made up of ingredient that includes azithromycin and substrate, and wherein said substrate contains following material: diluent 1-100%; Binding agent 0-30%; Disintegrating agent 0-10%; Lubricant 0-20%; Fluidizer 0-20%; Slow releasing agent 0-50% and conventional coloring agent, correctives, spice.
The present invention relates to contain the confection of following composition:
Described confection is made up of ingredient that includes azithromycin and substrate, and wherein said substrate contains following material: diluent 1-100%; Binding agent 0-20%; Disintegrating agent 0-10%; Lubricant 0-10%; Fluidizer 0-10%; Slow releasing agent 0-50% and conventional coloring agent, correctives, spice.
Preparation method of the present invention comprises following order and step, but following be not limitation of the invention:
1. the preparation method of buccal tablet: proportionally azithromycin is mixed with substrate; When described substrate was Icing Sugar, substrate contained but is not limited to one or more composition in sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, glucose, fructose, lactose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol, gelatinized corn starch, syrup, the maltose etc.; When described substrate was solid dispersion, substrate contained but is not limited to Polyethylene Glycol
(2000,4000,6000,8000,10000, 20000), polyoxyethylene stearate 40 esters, beta cyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition.
(1) takes by weighing an amount of Icing Sugar or other substrate, add water or binding agent, make suitable soft material, add the ingredient that contains azithromycin, stir, cut apart, shaping, drying.
(2) take by weighing an amount of Icing Sugar or other substrate, add the ingredient that contains azithromycin, add water or binding agent, stir, granulate, drying is shaped on tablet machine.
(3) take by weighing an amount of Icing Sugar or other substrate, add the ingredient that contains azithromycin,,, on tablet machine, be shaped then through cooled and solidified through being heated as the miscible or miscible state of semi-molten of fusion.
(4) take by weighing an amount of Icing Sugar or other substrate,, be cooled to 70-100 ℃, add the ingredient that contains azithromycin, stir, on tablet machine, be shaped through being heated as the miscible or miscible state of semi-molten of fusion.
2. the preparation of drop pill: proportionally azithromycin is mixed with substrate; Substrate is by containing Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more one-tenth in polyoxyethylene stearate 40 esters, beta cyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers are grouped into.Adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine, splash in 40 →-15 ℃ the condensing agent with suitable speed.Condensing agent can be any one or a few in liquid paraffin, methyl-silicone oil, the vegetable oil.
3. the preparation of confection: proportionally azithromycin is mixed with substrate; Matrix filler is to be grouped into by one or more the one-tenth that contains in sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, glucose, fructose, lactose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol, gelatinized corn starch, syrup, the maltose etc.
Take by weighing an amount of Icing Sugar or other substrate heat fused, be cooled to uniform temperature then after, add the ingredient contain azithromycin, stir, make into the plasticity magma, cut apart extrusion molding;
Azithromycin buccal lozenge of the present invention is compared with existing general formulation has following benefit:
1) the azithromycin concentration of raising diseased region improves its antibacterial ability.Medicine dissolves in the saliva in the oral cavity, enters around the oral cavity, pharyngeal and pharyngeal tonsil position.These medicines do not pass through hemodilution, form high local concentrations, strengthen antibacterial ability.Buccal lozenge of the present invention is compared with the capsule of prior art: aspect treatment pharyngitis and pharyngoamygdalitis, it is 80.6% that the clinical symptoms of azithromycin buccal tablet group and sign are improved percentage rate, and oral group 43.3% of azithromycin capsule illustrates that the curative effect of buccal tablet is better than oral formulations.Aspect treatment oral cavity infection disease, it is 48% that azithromycin buccal tablet group clinical symptoms and sign are improved percentage rate, and oral group 11.5% of azithromycin capsule illustrates that the curative effect of buccal tablet is better than oral formulations.
2) rapid-action.Medicine acts on pathological tissues immediately behind dissolved in oral cavity, saved to absorb the time limit that distributes.
3) convenient drug administration.To the injection of need through the parenteral route administration, change into by sucking the messenger drug thing at dissolved in oral cavity, directly act on diseased region then, produce therapeutic effect, avoided injection inject to approximately to patient bring painful and inconvenient.
4) production technology is oversimplified.Compare with injection, the production technology of buccal lozenge and the quality of production require all to be lower than injection, can obviously reduce production costs.
5) preparation of buccal lozenge of the present invention and prior art for preparing is relatively: matched group disintegration 16 ± 3 (minute), the dissolution of azithromycin only is 12 ± 5 (%) during disintegrate fully.And be 22 ± 4 the disintegration of buccal lozenge of the present invention (minute), the azithromycin dissolution is 86 ± 9 (%) during disintegrate fully.The result shows that buccal lozenge of the present invention has significantly improved the dissolution of medicine.
Specific implementation method
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
Embodiment 1-azithromycin confection
Prescription: Azithromycin Sulfate 62.5g, sucrose 915.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Azithromycin Sulfate 62.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 915.5 grams, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the mixture after sieving, stirred fast 10 minutes, place extrusion molding on the product shaping machine, every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 16-19 minute disintegration, and fully the dissolution during disintegrate is 95%-100%.
Embodiment 2-low sugar azithromycin confection (1)
Prescription: Azithromycin Sulfate 62.5g, sucrose 265.5g, oligofructose 300g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Azithromycin Sulfate 62.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 265.5g, oligofructose 300g, xylitol 300g, inulin 50g, mix, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the Azithromycin Sulfate 62.5g after sieving, stirred fast 10 minutes, place extrusion molding on the product shaping machine, every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 14-19 minute disintegration, and fully the dissolution during disintegrate is 95%-98%.
Embodiment 3-low sugar azithromycin buccal tablet (1)
Prescription: Azithromycin Sulfate 62.5g, gelatin 240g, glycerol 60g, water 60g, oligofructose 195.5g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-400.1g, mannitol 10g, magnesium stearate 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation gelatin 240g, glycerol 60g, water 60g mixed-matrix, drying adds Azithromycin Sulfate 62.5g, oligofructose 195.5g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-400.1g again, mannitol 10g, carbomer 934 P2g mixture, grind, cross 20 purpose sieves, granulate 60 ℃ of dryings with the second alcohol and water, add 10 gram magnesium stearate then, mixing places extrusion molding on the tablet machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin buccal tablet in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 25-32 minute disintegration, and fully the dissolution during disintegrate is 91%-94%.
Embodiment 4-azithromycin buccal tablet
Prescription: Azithromycin Sulfate 62.5g, hypromellose 100 grams, Polyethylene Glycol
6000837.5 gram, aspartame 0.1 gram, 1000 of amount of formulation.
Method: preparation hypromellose 100 grams, Polyethylene Glycol
6000837.5 gram, aspartame 0.1 gram mixed-matrix, heat fused is cooled to 80 ℃, adds Azithromycin Sulfate 62.5g, stirring and evenly mixing, and room temperature is cooled to solidifies, and granulates, and places extrusion molding on the tablet machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin sodium lozenge in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 58-77 minute disintegration, and fully the dissolution during disintegrate is 95%-99%.
Embodiment 5-low sugar azithromycin confection (2)
Prescription: Azithromycin Sulfate 62.5g, sucrose 265.5g, oligofructose 300g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-400.1g, mannitol 10g, carbomer 934 P 2g, 1000 of amount of formulation.
Method: preparation Azithromycin Sulfate 62.55g, citric acid 10g, food pigment-400.1g, mannitol 10g, carbomer 934 P 2g mixture grind, and cross 20 purpose sieves.Get sucrose 265.5g, oligofructose 300g, xylitol 300g, inulin 50g, mix, be heated to 140 ℃ of fusings, be cooled to and solidify, granulate, grind, cross 20 purpose sieves, add the azithromycin mixture after sieving, stirred fast 10 minutes, place extrusion molding on the product shaping machine, every heavy 2 grams.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 13-17 minute disintegration, and fully the dissolution during disintegrate is 96%-99%.
The preparation of embodiment 6-azithromycin buccal drop pills
Method: taking polyethylene glycol 40008.3 restrains respectively, polyethylene glycol 6000 7 grams, polyoxyethylene stearate 40 esters 1 gram, carbomer 2 grams, beta cyclodextrin 1 gram, poloxamer 0.5 gram, carboxymethyl starch sodium 0.5 gram, stearic acid 0.1 gram, sodium stearate 0.1 gram, glycerin gelatine 0.1 gram, glyceryl monostearate 0.1 gram, Lac 0.1 gram, polyoxyethylene monostearate 0.1 gram, polyethers 0.1 gram, mix homogeneously, add azithromycin raw material powder 30 grams again, fully mix, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, adopt homemade special drilling pill machine, regulate its water dropper temperature and make it remain on 85 ℃ (error＜2%); With the methyl-silicone oil is condensing agent, the refrigeration control system of regulating the drop pill machine makes the temperature of condensing agent remain on 20 →-5 ℃ (error＜5%), the system of dripping, wait to take out behind the type of being shrunk to, remove the surface condensation agent, dry, make the drop pill that contains azithromycin 60mg/ grain, carry out then rounding rate (%), dissolve scattered time limit (minute), the mensuration of the ball method of double differences different (%) and hardness, the rounding rate is 72% as a result, and dissolve scattered time limit 13-16 minute, the ball method of double differences was different from 10%, hardness is qualified, and fully the dissolution during disintegrate is 91%-94%.
Embodiment 7-low sugar azithromycin buccal tablet (2)
Prescription: Azithromycin Sulfate 62.5g, gelatin 240g, glycerol 40g, water 60g, oligofructose 242.5g, xylitol 192g, inulin 50g, citric acid 10g, food pigment-400.1g, mannitol 10g, magnesium stearate 10g, hypromellose 143 grams, 1000 of amount of formulation.
Method: preparation gelatin 240g, glycerol 40g, water 60g mixed-matrix, drying adds Azithromycin Sulfate 62.5g, oligofructose 242.5g, xylitol 192g, inulin 50g, citric acid 10g, food pigment-400.1g again, mannitol 10g, hypromellose 143 gram mixture, grind, cross 20 purpose sieves, granulate 60 ℃ of dryings with the second alcohol and water, add 10 gram magnesium stearate then, mixing places extrusion molding on the tablet machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin buccal tablet in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 47-58 minute disintegration, and fully the dissolution during disintegrate is 95%-97%.
Embodiment 8-low sugar azithromycin confection (3)
Prescription: Azithromycin Sulfate 62.5g, sucrose 145.5g, oligofructose 170g, xylitol 300g, inulin 50g, citric acid 10g, food pigment-400.1g, mannitol 10g, hypromellose 252 grams, 1000 of amount of formulation.
Method: preparation Azithromycin Sulfate 62.5g, citric acid 10g, food pigment-400.1g, mannitol 10g, hypromellose 252 gram mixture grind, and cross 20 purpose sieves.Get sucrose 145.5g, oligofructose 170g, xylitol 300g, inulin 50g, mix, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the mixture after sieving, stirred fast 10 minutes, place extrusion molding on the product shaping machine, every buccal tablet weighs 1 gram.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The result: be 82-91 minute disintegration, and fully the dissolution during disintegrate is 95%-99%.
Embodiment 9-buccal lozenge of the present invention and existing tablet are to the contrast test of the influence of azithromycin dissolution
1. technology one is substrate with the Icing Sugar
The control formulation preparation method: preparation azithromycin 62.5g, sucrose 917.5 grams, citric acid 10g, food pigment-400.1g, mannitol 10g mixture grinds, and crosses 20 purpose sieves, places extrusion molding on the product shaping machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The preparation method of buccal lozenge of the present invention: preparation azithromycin 62.5g, citric acid 10g, food pigment-40 0.1g, mannitol 10g mixture grinds, and crosses 20 purpose sieves.Get sucrose 917.5 grams, be heated to 140 ℃ of fusings, be cooled to 85 ℃, add the mixture after sieving, stirred fast 10 minutes, place extrusion molding on the product shaping machine, every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin confection in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The results are shown in Table 1, the present invention is the dissolution that the solid dispersion preparation technology of substrate can significantly improve azithromycin with the Icing Sugar.
Table 1, the present invention are the influence of the solid dispersion preparation technology of substrate to the azithromycin dissolution with the Icing Sugar
＊p＜0.01
2. technology two is substrate with the surfactant
Control formulation preparation method: preparation azithromycin 62.5g, hypromellose 100 grams, Polyethylene Glycol
6000837.5 gram, aspartame 0.1 gram mixed-matrix, stirring and evenly mixing is granulated, and places extrusion molding on the tablet machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin sodium lozenge in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The preparation method of buccal lozenge of the present invention: preparation hypromellose 100 grams, Polyethylene Glycol
6000837.5 gram, aspartame 0.1 gram mixed-matrix, heat fused is cooled to 80 ℃, adds azithromycin 62.5g, stirring and evenly mixing, and room temperature is cooled to solidifies, and granulates, and places extrusion molding on the tablet machine, and every buccal tablet weighs 2 grams.Measure the disintegration of azithromycin sodium lozenge in 37 ℃ of 900ml water and the dissolution during complete disintegrate then.
The results are shown in Table 2, the present invention is the dissolution that the solid dispersion preparation technology of substrate can significantly improve azithromycin with the Icing Sugar.
Table 2, the present invention are the influence of the solid dispersion preparation technology of substrate to the azithromycin dissolution with the surfactant
＊p＜0.01
The embodiment 10-embodiment of the invention 4 azithromycin buccal tablets and azithromycin capsule of the prior art are in the comparative test to the therapeutical effect effect of acute pharyngitis and acute pharyngoamygdalitis
Medicine: trial target: the embodiment of the invention 4 azithromycin buccal tablet 0.125g/ sheets, reference substance: the azithromycin capsule 0.125g/ grain that Beijing Taiyang Pharmaceutical Co., Ltd. produces
Method: choose acute pharyngitis and acute pharyngoamygdalitis case, be divided into oral group of azithromycin capsule, the azithromycin buccal tablet is sucked group.Each group awards 8/day of 8 slices/day of embodiment 4 azithromycin buccal tablets or azithromycin capsules respectively.Oral group with per 6 hours once, each 2, through water delivery service.Suck group with per 6 hours once, 2 of each buccal continuously, every tablet of medicine time of oral cavity including reservation with greater than 30 minutes.Each is organized case and all observed 48 hours, improves situation respectively at observation in 4,8,16,24,48 hours and record clinical symptoms and sign after the administration.By writing down the case load that each time point clinical symptoms and sign are improved, analyze the therapeutic effect of buccal lozenge to acute pharyngitis and acute pharyngoamygdalitis.Clinical symptoms and sign be improved as that heating is disappeared, pharyngalgia disappears, pharyngeal or tonsil is congested alleviates three indexs and occurs one at least.
The result: by table 3 as seen, by the laboratory observation to 61 routine cases, it is azithromycin buccal tablet group 80.6% that 48 hours clinical symptoms of taking medicine and sign are improved percentage rate, and oral group 43.3% of azithromycin capsule illustrates that the curative effect of buccal tablet is better than oral formulations.
The efficacy test result of study of table 3, buccal lozenge of the present invention
＊p＜0.05
The embodiment 11-embodiment of the invention 4 azithromycin buccal tablets and azithromycin capsule of the prior art are in the comparative test to the therapeutical effect effect of oral cavity infectious disease
Medicine: trial target: the embodiment of the invention 4 azithromycin buccal tablet 0.125g/ sheets, reference substance: the azithromycin capsule 0.125g/ grain that Beijing Taiyang Pharmaceutical Co., Ltd. produces
Method: choose bacterial infection periodontitis case, be divided into oral group of azithromycin capsule, the azithromycin buccal tablet is sucked group.Each group awards 4/day of 4 slices/day of embodiment 4 azithromycin buccal tablets or azithromycin capsules respectively.Oral group with per 6 hours once, each 2, through water delivery service.Suck group with per 6 hours once, 2 of each buccal continuously, every tablet of medicine time of oral cavity including reservation with greater than 30 minutes.Each is organized case and all observed 3 days, improves situation respectively at observation in 1,2,3 day and record clinical symptoms and sign after the administration.By writing down the case load that each time point clinical symptoms and sign are improved, analyze the therapeutic effect of buccal lozenge to the bacterial infection periodontitis.Clinical symptoms and sign are improved as that gingival hemorrhage alleviates, gingiva hyperemia alleviates two indexs and occurs one at least.
The result: by table 4 as seen, by the laboratory observation to 51 routine cases, it is azithromycin buccal tablet group 48% that 3 days clinical symptoms of taking medicine and sign are improved percentage rate, and oral group 11.5% of azithromycin capsule illustrates that the curative effect of buccal tablet is better than oral formulations.
The efficacy test result of study of table 4, buccal lozenge of the present invention
＊p＜0.05
Claims (10)
1. a drug quality that improves treatment pharyngitis, pharyngoamygdalitis and oral cavity infection disease is the buccal lozenge of main ingredient with azithromycin, it is characterized in that described buccal lozenge is made up of ingredient that includes azithromycin and salt derivative thereof and substrate.
2. buccal lozenge according to claim 1, be 10-100 minute the disintegration of described azithromycin buccal lozenge.
3. buccal lozenge according to claim 2, be 20-60 minute the disintegration of described azithromycin buccal lozenge.
4. the buccal lozenge of azithromycin according to claim 1, it is characterized in that: described buccal lozenge type comprises buccal tablet, drop pill, confection.
5. the preparation method of the buccal tablet in the described buccal lozenge that contains azithromycin of claim 4, it is characterized in that: described buccal tablet is through being heated as the miscible or miscible state of semi-molten of fusion by the ingredient that contains azithromycin and substrate, then through cooled and solidified, and then make described buccal tablet.
6. the preparation method of the drop pill in the described buccal lozenge that contains azithromycin of claim 4, it is characterized in that: proportionally azithromycin is mixed with substrate, adopt water-bath, oil bath or other mode of heating, mixed material is heated to fusion, stir, insert on the drop pill machine with suitable speed, splash in 40 →-15 ℃ the condensing agent and be shaped.
7. the preparation method of the confection in the described buccal lozenge that contains azithromycin of claim 4, it is characterized in that: described confection be earlier with substrate through being heated as the miscible state of fusion, then through being cooled to semi-solid, add the ingredient that contains azithromycin then, stirring and evenly mixing, make into the plasticity magma, cut apart, extrusion molding.
8. claim 5 or 6 preparation method, wherein said substrate is one or more compositions that comprise in Polyethylene Glycol, polyoxyethylene stearate 40 esters, beta cyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers, the Icing Sugar.
9. according to claim 5,6,7 described preparation methoies, it is characterized in that: described substrate comprises one or more medicinal slow releasing agent and coloring agent, correctives, spice and other pharmaceutic adjuvant.
10. the application of the buccal lozenge of claim 1 in preparing the medicine that can improve treatment pharyngitis, pharyngoamygdalitis and oral cavity infection disease drug quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNA2007100871394A CN101269085A (en) | 2007-03-22 | 2007-03-22 | Oral preparation containing azithromycin, preparation method and application thereof |
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| CNA2007100871394A CN101269085A (en) | 2007-03-22 | 2007-03-22 | Oral preparation containing azithromycin, preparation method and application thereof |
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| CN101269085A true CN101269085A (en) | 2008-09-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107233324A (en) * | 2017-06-13 | 2017-10-10 | 江苏黄河药业股份有限公司 | A kind of azithromycin formulations and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107233324A (en) * | 2017-06-13 | 2017-10-10 | 江苏黄河药业股份有限公司 | A kind of azithromycin formulations and preparation method thereof |
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