CN1981765A - Medicament composition of cefpodoxime proxetil and cyclodextrin and preparation method thereof - Google Patents

Medicament composition of cefpodoxime proxetil and cyclodextrin and preparation method thereof Download PDF

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CN1981765A
CN1981765A CNA2006101627063A CN200610162706A CN1981765A CN 1981765 A CN1981765 A CN 1981765A CN A2006101627063 A CNA2006101627063 A CN A2006101627063A CN 200610162706 A CN200610162706 A CN 200610162706A CN 1981765 A CN1981765 A CN 1981765A
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cyclodextrin
cefpodoxime proxetil
pharmaceutical composition
agent
cefpodoxime
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A·K·班塞尔
K·凡苏库玛
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Ranbaxy Laboratories Ltd
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Ranbaxy Laboratories Ltd
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Abstract

A medication compound, which include cyclodextrin and cephalosporin ester's clathrate; this invention alao related to the method to produce it.

Description

Pharmaceutical composition of Cefpodoxime Proxetil and cyclodextrin and preparation method thereof
Technical field
The present invention relates to comprise the pharmaceutical composition of clathrate of the Cefpodoxime Proxetil (cefpodoxime proxetil) of cyclodextrin, the present invention also relates to described preparation of compositions method.
Background technology
Cefpodoxime is a third generation cephalosporin, its chemistry (+) by name-(6R, 7R)-7-[2-(2-amino-4-thiazolyl)-2-{ (Z) methoxyimino } acetylamino]-3-methoxy-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid-1-(isopropoxy carbonyl oxygen base) ethyl ester.Cefpodoxime and its pharmaceutically-acceptable acid addition such as U.S. Pat 4,486,425 are described, and it is for reference intactly to incorporate this patent into this paper at this.Cefpodoxime is stable for the hydrolysis by modal plasmid-mediated beta-lactamase.This medicine has broad-spectrum antibacterial activity, and gram negative bacteria and gram positive bacteria are all had antibacterial activity, simultaneously with other broad-spectrum cephalosporin the suitable well tolerable linearity curve of Sihe is mutually arranged again for the generation of side reaction and seriousness.Like this, it be at present in adult patient and pediatric patient widely used beta-lactam carry out a kind of effective replacement in the acquired infection of experiential therapy large scope colony.Cefpodoxime carries out oral with the form of its prodrug Cefpodoxime Proxetil, described cefpodoxime takes off ester by mucous membrane of small intestine, discharges active part, cefpodoxime.
According to the biopharmacy classification of medicine, Cefpodoxime Proxetil is classified as IV class medicine, has bad dissolubility and bad permeability.Be considered to be subjected to the restriction of dissolution rate from the bioavailability of the Cefpodoxime Proxetil of pharmaceutical composition, its absolute oral administration biaavailability only is about 50%.Cefpodoxime is hydrophobic, and the contact angle of itself and water is greater than 95 degree.Because Cefpodoxime Proxetil can form gelatinous agglomerate when contacting with aqueous medium, so its wettability (S.T.P.Pharma Sciences such as Hamaura T., 1995 have further been hindered; 5 (4): 324).Formed gel disintegrate gets very poor, thereby has slowed down stripping, and therefore greatly reduces from the absorption of gastrointestinal tract to cefpodoxime.Except poor solubility, it is under the influence of alkaline pH, and the degraded fast by the gastrointestinal tract non-specific enzyme.
Develop pharmaceutical composition with acceptable stripping property and stability, and the bioavailability characteristics that increases them in view of the above challenging task always.An approach that improves the dissolubility property of this class medicine relates to the use solid dispersion.For example, WO04105728 has disclosed the solid dispersion of the Cefpodoxime Proxetil in carrier.
Other approach comprises and uses various solubilizing agents, for example, and those that report as following document: D.D.Chow etc., Int.J.Pharm., 28,95-101,1986; F.A.Menard etc., Drug Dev.Ind.Pharm., 14 (11), 1529-1547,1988; F.J.Otera-Espinar etc., Int.J.Pharm., 75,37-44,1991; With Berand M.Markarian etc., the open EP of European patent in July, 0274444,1988.
Many document illustrations use cyclodextrin and their derivant to prepare the clathrate of the medicine of poor solubility, for example, D.Duchene, cyclodextrin and their commercial Application (Cyclodextrins and theirIndustrial uses), Editions de Sante, Paris, 1987, the 6th chapter (211-257), the 8th chapter (297-350), the 10th chapter (393-439); D.Duchene etc., Acta Pharma Technol.36 (1) 6,1-6,1990; D.Duchene etc., Drug Dev.Ind.Pharm., 16 (17), 2487-2499,1990; C.Hunter etc., European patent communique EP in December, 0346006,1988.US 4,727,064 and US 5,024,998 also disclosed the cyclodextrin derivative that uses chemical modification.
US 4,883, and 785 have disclosed by the polyene antifungal agent, as amphotericin B, and cyclodextrin, comprise the clathrate (complex) that gamma-cyclodextrin forms.The clathrate that comprises amphotericin B is compared water solublity and the stability that demonstrates improvement with amphotericin B antifungal compositions of the prior art.
US 4,616, and 808 have disclosed and are used for oral antibiotic solid composite, and it comprises liposoluble cephalosporin compound and cyclodextrin.Described compositions greatly increases the interior absorbability of body of the non-ester-formin of cephalosporin compound.
Use the cyclodextrin clathrate of medicine increase they dissolubility and stability and and then the bioavailability that increases them be known in the art.
Summary of the invention
We find that now this approach can be used for increasing the dissolubility and the stability of Cefpodoxime Proxetil especially, thereby the bioavailability of Cefpodoxime Proxetil is obviously increased.
Therefore, one aspect of the present invention provides the Cefpodoxime Proxetil that comprises Cefpodoxime Proxetil and cyclodextrin pharmaceutical composition.
Another aspect of the present invention provides the Cefpodoxime Proxetil that comprises Cefpodoxime Proxetil and beta-schardinger dextrin-pharmaceutical composition.
Another aspect of the present invention provides the Cefpodoxime Proxetil that comprises Cefpodoxime Proxetil and hydroxypropyl pharmaceutical composition.
Another aspect of the present invention provides Cefpodoxime Proxetil preparation of drug combination method, comprises Cefpodoxime Proxetil is mixed with cyclodextrin, and is processed into the step of suitable dosage form.
Another aspect of the present invention provides a kind of bioavailability that makes Cefpodoxime Proxetil to be improved to 1.25 times or higher method of the bioavailability of conventional peroral dosage form, comprises the clathrate that uses Cefpodoxime Proxetil and cyclodextrin.
Another aspect of the present invention provides the method for treatment mammal bacterial infection, comprises the Cefpodoxime Proxetil pharmaceutical composition that mammal is comprised Cefpodoxime Proxetil and cyclodextrin.
The specific embodiment
Cefpodoxime Proxetil is the very poor medicine of dissolubility, and therefore, its dissolution rate remains limited for it absorbs.The absolute bioavailability of commercially available Cefpodoxime Proxetil tablet only be cefpodoxime sodium venous transfusion about 50%.The bad dissolubility of Cefpodoxime Proxetil also is attributable to its bad wettability, can further form gel when it contacts with aqueous medium.Undoubtedly be, bad dissolubility remains main cause, other reason comprises its poor stability because it before entering whole body (presystemic) is degraded into cefpodoxime acid, and the absorbability of cefpodoxime acid is very poor.
Therefore Cefpodoxime Proxetil should discharge from pharmaceutical composition with very soluble form and be beneficial to quick stripping and reduce the mechanism of degradation meeting that absorbs site.Can solve this all class problems with the cyclodextrin inclusion compound Cefpodoxime Proxetil, thus its bioavailability compare with commercially available dosage form tangible increase arranged.
Caused the wettability of Cefpodoxime Proxetil to increase with cyclodextrin to the Cefpodoxime Proxetil enclose.This also helps may be in the disintegrate of the gel layer of formation on every side of Cefpodoxime Proxetil granule.Thereby the enclose of cyclodextrin is by increasing its effective dissolubility and increasing the bioavailability of Cefpodoxime Proxetil by increasing dissolution rate and stripping degree.In addition, cover by molecule is provided, the clathration of cyclodextrin is got up the Cefpodoxime Proxetil bag of molecular level, and itself and various degradation process are kept apart.Further be that the various substituent groups on the cyclodextrin structure are by reducing the hydrolysis that the affinity of enzyme has been slowed down enzyme.The dissolution rate that improves and the degraded of minimizing have increased can reach the biological barrier surface, and as the amount of the Cefpodoxime Proxetil at mucous membrane of small intestine place, at this, cefpodoxime distributes and enters film and do not disturbed by the lipid layer of barrier, thereby has improved overall bioavailability.
According to the present invention, its bioavailability can be improved as 1.25 times of bioavailability of conventional peroral dosage form or higher to the Cefpodoxime Proxetil enclose with cyclodextrin.The effect of the Cefpodoxime Proxetil of the increase that the Cefpodoxime Proxetil dissolubility that is increased by cyclodextrin causes and potential (that is, reducing the active required dosage of optimal treatment) are by making medicine than the toxicity that promptly effectively can reduce medicine under the low dosage.But the Cefpodoxime Proxetil that gives low amount can reach the blood drug level with the regular dosage form analogy.Therefore, the cost performance of this based composition is good, and reduces dosage and pile up the toxicity problem that causes.In addition, it helps to suppress the bitterness of Cefpodoxime Proxetil.
From its angle of simplifying most, pharmaceutical composition of the present invention comprises Cefpodoxime Proxetil, cyclodextrin and at least a pharmaceutically inert excipient.
The amount of Cefpodoxime Proxetil can account for about 10%w/w of composition total weight to about 90%w/w, and particularly about 25%w/w is to about 75%w/w.
Cyclodextrin (CD) is cyclic oligosaccharide, and it contains at least six D-(+) glucopyranose unit that connect by α (1,4) glycosidic bond.They have lipophilic inner chamber and hydrophilic outer surface, can form non-covalent clathrate with various objects (medicine).Cyclodextrin of the present invention can comprise the combination of one or more cyclodextrin.Various factors as the type of cyclodextrin, the temperature and the method for preparation, has influenced the formation and the performance of clathrate.Suitable cyclodextrin comprises cyclodextrin α, the β and the γ CDs (having 6,7 or 8 glucose units separately) and their pharmaceutically acceptable derivates that form naturally of three kinds of ring sizes and different solubility.Particularly, can use widely used β-CD and its derivant on pharmaceutical industry already, because this β-CD is easy to get, and the size in chamber is fit to the various medicines in the widest scope.The pharmaceutically acceptable derivates of cyclodextrin comprises alkyl or dialkyl group, hydroxyalkyl (as hydroxypropyl), carboxylic acid amides, diethyllaminoethyl, carboxymethyl and dihydroxyalkyl (as, dihydroxypropyl), sulfo group butyl (suflobutyl) derivant or the like.Specific example comprises ethoxy-β-CD, hydroxy propyl-Beta-CD, sulfo group butyl ether-β-CD, methyl-β-CD, dimethyl-β-CD, random dimethylated-β-CD, random methylated-β-CD, carboxyl methyl-β-CD, carboxyl Methylethyl-β-CD, diethyl-β-CD, three-O-methyl-β-CD, three-O-ethyl-β-CD, three-O-butyryl-β-CD, three-O-valeryl-β-CD, two-O-hexanoyl-β-CD, glucityl-β-CD, malt-base-β-CD, 2-hydroxyl-3-trimethyl-ammonio propyl group (ammoniopropyl)-β-CD.The mol ratio of Cefpodoxime Proxetil and cyclodextrin is about 1: 9 to about 9: 1.
Inert excipient pharmaceutically of the present invention comprises one or more water-soluble polymer, solvent, diluent, binding agent, disintegrating agent, surfactant, lubricant/slippage agent, stabilizing agent, plasticizer, coloring agent, flavoring agent, suspending agent, sweeting agent, buffer agent or the like.
Water-soluble polymer increases the solubilising effect of cyclodextrin by increasing apparent clathrate stability constant.The example of water-soluble polymer comprises hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, polyacrylic acid, cross-linked polyacrylic acid polymer, polyvinyl pyrrolidone or the like.
Solvent can improve the solubilising and the stabilizing effect of cyclodextrin.The example of suitable cosolvent comprises Polyethylene Glycol, propylene glycol, ethanol, methanol, acetone, isopropyl alcohol, dichloromethane, hydrochloric acid, sodium hydroxide, water of one or more different stages or the like.
The example of diluent comprises calcium carbonate, secondary calcium phosphate, tertiary calcium phosphate, calcium sulfate, microcrystalline Cellulose, cellulose powder, dextrates, dextrin, dextrose excipient, fructose, Kaolin, lactose, lactose, mannitol, sorbitol, pre-granular starch, sucrose, compressible sugar, berry sugar (sugarconfectioner) or the like.
The example of binding agent comprises methylcellulose, hydroxypropyl cellulose, HPMC, gelatin, arabic gum, ethyl cellulose, polyvinyl alcohol, amylopectin, pre-granular starch, agar, Tragacanth, sodium alginate, propylene glycol or the like.
Examples of disintegrants comprise the low hydroxypropyl cellulose (L-HPC) that replaces, sodium starch glycollate, carboxymethyl cellulose, carboxymethylcellulose calcium, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose A-type (corscarmellose sodium A-type, Ac-di-sol), starch, microcrystalline Cellulose, hydroxypropyl starch, the pre-granular starch of part or the like.
Surfactant can be selected from the surfactant of anion, cation or nonionic.Suitable anion surfactant comprises the material that contains carboxylate, sulfonate and sulfate ion, as sodium lauryl sulphate (SLS), sodium laurate, dialkyl sodium sulfosuccinate (particularly two-(2-ethylhexyl) sodium sulfosuccinates), sodium stearate, potassium stearate, enuatrol or the like.Suitable cationic surfactants comprises the material that contains long chain cation, as benzalkonium chloride, two-2-ethoxy oleamide or the like.Suitable ionic surfactant pack is drawn together the polyethylene glycol oxide sorbitan fatty ester; Aliphatic alcohol is as lauryl alcohol, hexadecanol and octadecanol; Glyceride is as monoglyceride, two glyceride and the triglyceride of natural formation; The fatty acid ester of aliphatic alcohol; The glyceride type of polyglycolic acid esterification is as Gelucire; Polyox-yethylene-polyoxypropylene block copolymer is as Poloxamer and other alcohols, as propylene glycol, Polyethylene Glycol, sorbitan, sucrose and cholesterol.
The example of lubricant and slippage agent comprises sucrose ester, microwax, yellow Cera Flava, white beeswax of gluey anhydride silica, stearic acid, magnesium stearate, calcium stearate, Pulvis Talci, castor oil hydrogenated, fatty acid or the like and their combination.
The example of stabilizing agent comprises pH regulator agent, anti-microbial preservative, antioxidant or the like.The example of regulator comprises acid, alkali and buffer agent.Suitable acid can comprise any organic acid or mineral acid, example hydrochloric acid, phosphoric acid, lactic acid or the like.Suitable alkali can comprise any organic base or inorganic base, as diethanolamine, triethanolamine, meglumin, trimethanolamine, diethanolamine, 1, L-lysine, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium oxide, magnesium hydroxide, ammonia or the like.Suitable reducing comprises sodium orthophosphate or sodium orthophosphate dimetallic, sodium ascorbate, sodium citrate, lactate or the like.The example of anti-microbial preservative comprises benzylalcohol, phenethanol, phenyl phenol, sodium benzoate, nipagin, propyl parabene, Butyl Chemosept or the like.Examples of antioxidants comprises propyl gallate, demercaprol, Butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid hexadecane ester, sodium pyrosulfite, tocopherol (as alpha-tocopherol (vitamin E)) and/or its ester or the like.
The example of plasticizer comprises Polyethylene Glycol, triethyl citrate, glyceryl triacetate, diethyl phthalate, dibutyl sebacate or the like.
The example of flavoring agent comprise any FDA permission, for oral pigment, like Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, orange, Rubus corchorifolius, Ribes nigrum L., Fructus Fragariae Ananssae, caramel chocolate (Caramel Chocolate), Herba Menthae (Mint Cool), comprise the flavoring substance of the dreamlike flavoring agent (Fantasy flavors) etc. of Flos Jasmini Nudiflori Fructus Citri Limoniae (yellow plum lemon), aromatic substance, Oleum menthae, wintergreen oil.
The example of coloring agent comprise any FDA permission, for oral material, red or the like as ferrum oxide, tartrazine lake, quinoline yellow lake, sunset yellow color lake and erythrosine color lake, Ponceaux color lake, Allura.
The example of suspending agent comprises polysaccharide, as Tragacanth, xanthan gum, bentonite, arabic gum; Cellulosic lower alkyl ether, as the hydroxyl and the carboxy derivatives of cellulose ether, starch (as corn starch, pre-granulating starch); Microcrystalline Cellulose; Silicon dioxide; Polyvinyl pyrrolidone or the like.
Suitable sweeting agent comprises monosaccharide, as glucose (dextrose), fructose (levulose); Disaccharide is as sucrose, lactose, maltose, cellobiose; Other saccharide is as ribose, glycerol, Sorbitol, xylitol, mannitol, erythritol, inositol, lactose monohydrate, propylene glycol, galactose, mannose, xylose, rhamnose, glutaraldehyde, Nulomoline, mannitol, Polyethylene Glycol, glycerol aspartame, glucide or sorbitol solution or the like.
The example of buffer agent comprises any Acid-Base combination, as the combination of succinic acid, tartaric acid, lactic acid or citric acid and sodium hydroxide or sodium hydrogen phosphate.
The method of the clathrate of preparation cyclodextrin and Cefpodoxime Proxetil can comprise the known technology of any routine, as grinding altogether, kneading, solvent evaporation, co-precipitation, spray drying, lyophilizing or the like.
In one embodiment, the clathrate of Cefpodoxime Proxetil and cyclodextrin can prepare by the method that comprises the following steps: continuing under the stirring Cefpodoxime Proxetil and cyclodextrin to be mixed in solvent, remove by filter the material of not complexation, lyophilizing filtrate, the solid clathrates of formation Cefpodoxime Proxetil and cyclodextrin.
In another embodiment, Cefpodoxime Proxetil and cyclodextrin can prepare by the method that comprises the following steps: mediate the Cefpodoxime Proxetil of pasty state form and the mixture of cyclodextrin, the dry solid clathrates that forms Cefpodoxime Proxetil and cyclodextrin.
Perhaps, the clathrate of Cefpodoxime Proxetil and cyclodextrin can be adsorbed on pharmaceutically the inert excipient.
The Cefpodoxime Proxetil that obtains with above-mentioned any embodiment and the clathrate of cyclodextrin be the technology of available routine also, as pulverizing, mixing, granulation, fusion, gluing, filling, drying, mold pressing, dipping, coating, compress, extrude-become nodularization (spheronization) etc. to be processed into peroral dosage form.
Suitable peroral dosage form comprises tablet, capsule, suspending agent/dispersant, solution, dry syrup or the like.
By can confirm the formation of the clathrate of Cefpodoxime Proxetil and cyclodextrin such as mensuration dissolution rate, differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), thermo gravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), high pressure liquid chromatography technology such as (HPLC).
The present invention also is further elaborated by the following example, and described embodiment only supplies example usefulness, is not to be used to limit scope of the present invention.
Embodiment number Component Embodiment 1 Embodiment 2 Embodiment 3 Embodiment 4
Percent (%) W/W
1. Cefpodoxime Proxetil 33.33% 50% 50% 40%
2. Beta-schardinger dextrin- 66.67% 50% - -
3. Hydroxypropyl beta-CD - - 50% -
4. Sulfo group butyl ether β-cyclodextrin - - - 60%
Process:
1. Cefpodoxime Proxetil and cyclodextrin (component 2,3 or 4) are added 0.1N HCl solution, at a high speed (1000 rev/mins) stir about 12-24 hour.
2. be settled out the overdose of medicine thing by pH being increased to about 5.5 to about 6.5 with dilute sodium hydroxide.
3. the precipitation medicine that dissociates and of filtration step 2, lyophilizing filtrate obtains the clathrate of Cefpodoxime Proxetil and cyclodextrin.
Be stored under 40 ℃ according to the formed clathrate of embodiment 3 compositionss, in 2 weeks, analyze Cefpodoxime Proxetil at regular intervals, find that the content of Cefpodoxime Proxetil is at least 90% with effective HPLC method.
Under fasted conditions (can arbitrarily drink water), in male Sprague-Dawely rat (body weight: 250-275 gram), assess the clathrate of Cefpodoxime Proxetil and hydroxypropyl (T) with respect to Cepodem with the dosage of 10mg (being equal to cefpodoxime acid)/kg body weight TMUsefulness in the body of 100 tablets (Ranbaxy Laboratories Ltd.'s product).The all experiments carried out on animal and process are all carried out according to the scheme of Ethics Committee of animal mechanism (theAnimal Institutional Ethical Committee) permission.Each preparation gives oral under the help that has brinish oral standard pin with given dose.0.5,1, located to collect blood sample (0.4-0.5ml) in 1.5,2,3,4,6,8,12 and 24 hours.Centrifugal sample is isolated blood plasma and medicine inclusions, with effective HPLC methods analyst.From the data of gained, calculate pharmacokinetic parameter C Max(maximum plasma concentration), T Max(reaching the dense required time of maximum blood medicine), AUC 0-t(at blood drug level to the area under 0 hour time graph when collecting last sample) and AUC 0-α(at blood drug level to from 0 hour area under the infinitely-great time graph).Use MS-Excel TMReturn software PC-NONLIN with non-linearity TMAnalytical data.Result of study is as shown in the table.
Dosage form C max (ng/ml) T max(hour) AUC 0-∝ The relative percent (%) of bioavailability (T/R)
R 3994± 676 0.75± 0.10 8372± 1003 140.21
T 4104± 999 0.98± 0.19 11738± 1378
The above results has clearly illustrated that preparation Cefpodoxime Proxetil and the importance of cyclodextrin clathrate on the oral administration biaavailability that improves Cefpodoxime Proxetil.

Claims (11)

1. Cefpodoxime Proxetil pharmaceutical composition, it comprises Cefpodoxime Proxetil and cyclodextrin.
2. pharmaceutical composition as claimed in claim 1, wherein Cefpodoxime Proxetil accounts for about 10%w/w of described compositions to about 90%w/w.
3. pharmaceutical composition as claimed in claim 1, wherein cyclodextrin is selected from alpha-cyclodextrin, beta-schardinger dextrin-, one or more in gamma-cyclodextrin and δ-cyclodextrin and their pharmaceutically acceptable derivates.
4. pharmaceutical composition as claimed in claim 3, wherein cyclodextrin is to be selected from ethoxy-β-CD, hydroxy propyl-Beta-CD, sulfo group butyl ether-β-CD, methyl-β-CD, dimethyl-β-CD, random dimethylated-β-CD, random methylated-β-CD, carboxymethyl-β-CD, carboxymethyl ethyl-β-CD, diethyl-β-CD, three-O-methyl-β-CD, three-O-ethyl-β-CD, three-O-butyryl-β-CD, three-O-valeryl-β-CD, two-O-hexanoyl-β-CD, glucityl-β-CD, the beta-cyclodextrin derivative of malt-base-β-CD and 2-hydroxyl-3-trimethyl-ammonio propyl group (ammoniopropyl)-β-CD.
5. pharmaceutical composition as claimed in claim 1, wherein the molar ratio range of Cefpodoxime Proxetil and cyclodextrin is about 1: 9 to about 9: 1.
6. the arbitrary described pharmaceutical composition of claim as described above, wherein pharmaceutical composition also comprises one or more inert excipients pharmaceutically, is selected from one or more water-soluble polymer, solvent, diluent, binding agent, disintegrating agent, surfactant, lubricant/slippage agent, stabilizing agent, plasticizer, coloring agent, flavoring agent, suspending agent, sweeting agent and buffer agent.
7. the described pharmaceutical composition of arbitrary as described above claim, it is prepared by the method that comprises the following steps: make the combination of Cefpodoxime Proxetil and cyclodextrin, and be processed into suitable dosage form.
8. pharmaceutical composition as claimed in claim 7, wherein said dosage form is selected from tablet, capsule, suspending agent/dispersant, solution and dry syrup.
9. the bioavailability with Cefpodoxime Proxetil is improved to 1.25 times or higher method of conventional peroral dosage form, and this method comprises the clathrate that uses Cefpodoxime Proxetil and cyclodextrin.
10. a method for the treatment of the mammal bacterial infection comprises giving the Cefpodoxime Proxetil pharmaceutical composition to mammal, and described pharmaceutical composition comprises Cefpodoxime Proxetil and cyclodextrin.
11. as the described Cefpodoxime Proxetil pharmaceutical composition of embodiment.
CNA2006101627063A 2005-11-23 2006-11-23 Medicament composition of cefpodoxime proxetil and cyclodextrin and preparation method thereof Pending CN1981765A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008110079A1 (en) * 2007-03-14 2008-09-18 Nanjing Normal University Medical composition containing cyclodextrin inclusion compound of cefdinir and its preparation method
WO2008110080A1 (en) * 2007-03-14 2008-09-18 Nanjing Normal University Medical composition containing cyclodextrin inclusion compound of cefixime and its preparation method

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008110079A1 (en) * 2007-03-14 2008-09-18 Nanjing Normal University Medical composition containing cyclodextrin inclusion compound of cefdinir and its preparation method
WO2008110080A1 (en) * 2007-03-14 2008-09-18 Nanjing Normal University Medical composition containing cyclodextrin inclusion compound of cefixime and its preparation method

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