CN101278914A - Cefpodoxime proxetil suspension composition and preparation thereof - Google Patents

Cefpodoxime proxetil suspension composition and preparation thereof Download PDF

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CN101278914A
CN101278914A CNA2008100868131A CN200810086813A CN101278914A CN 101278914 A CN101278914 A CN 101278914A CN A2008100868131 A CNA2008100868131 A CN A2008100868131A CN 200810086813 A CN200810086813 A CN 200810086813A CN 101278914 A CN101278914 A CN 101278914A
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weight portion
pharmaceutically acceptable
cefpodoxime proxetil
cefpodoxime
gan
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CN101278914B (en
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黄合
全丹
张建军
高缘
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HAINAN SANYE PHARMACEUTICAL CO Ltd
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HAINAN SANYE PHARMACEUTICAL CO Ltd
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Abstract

The invention relates to a cefpodoxime proxetil dry suspension composition and a preparation method thereof. The invention provides the cefpodoxime proxetil dry suspension composition, containing 100 parts by weight of the cefpodoxime proxetil and 20 to 500 parts by weight of the glyceryl behenate. The invention also provides the preparation method of the dry suspension composition. The dry suspension composition of the invention is capable of reducing bitterness of the cefpodoxime proxetil remarkably and improving compliance of a clinical patient, thereby being suitable for a child to take a drug.

Description

Cefpodoxime proxetil suspension composition and preparation method thereof
Technical field
The present invention relates to a kind of dry suspension composition and method of making the same, be specifically related to Cefpodoxime proxetil suspension composition and preparation method thereof.
Background technology
Cefpodoxime Proxetil is oral wide spectrum third generation cephalosporin, enters in the body and brings into play antibacterial action after nonspecific esterase is hydrolyzed to cefpodoxime, and is all effective to gram positive bacteria and negative bacterium.Clinical responsive microbial upper respiratory tract infection, lower respiratory infection, simple property urinary tract infection, simple property skin and the skin soft-tissue infection etc. of being used for.
Dry suspension is the important clinical dosage form of Cefpodoxime Proxetil, is particularly suited for child and gerontal patient's medication.The Cefpodoxime Proxetil suspensoid of external listing has two kinds: liquid suspension and solid-state dry suspension, dry suspension need to add before oral administration to be taken after an amount of water disperses again again.The suspension formulations product as
Figure A20081008681300031
, dry suspension product such as Orelox TMAnd Banan, the prescription composition of these formulation products can get by modes such as U.S. FDA or product webs, has as seen wherein added certain essence and sweeting agent in the hope of reaching the purpose of adjusting the suspensoid mouthfeel.
Yet, we show by a large amount of experiments, Cefpodoxime Proxetil is a kind of medicine that remarkable bitterness is arranged, add conventional methods such as essence, sweeting agent and can not effectively cover its bitterness, this makes the patient produce the resistance sense to the clinical application of existing Cefpodoxime proxetil suspension, has reduced the compliance of patient's clinical application.
Therefore, press for a kind of technology that can significantly improve the Cefpodoxime Proxetil bitterness at present, it can significantly improve the bitterness of Cefpodoxime proxetil suspension, improves patient's clinical application compliance, and is more suitable for the medication of child patient.
Summary of the invention
The purpose of this invention is to provide a kind of dry suspension compositions that can significantly improve the Cefpodoxime Proxetil bitterness.
Another object of the present invention provides a kind of method of making above-mentioned Cefpodoxime proxetil suspension composition.
Therefore, the invention provides a kind of remarkable dry suspension compositions of improving the Cefpodoxime Proxetil bitterness, it comprises:
The Cefpodoxime Proxetil of 100 weight portions;
The Gan You behenic acid ester of 25-500 weight portion.
In the preferred embodiment of the present invention, described Cefpodoxime proxetil suspension composition also comprises the additive of 500-6000 weight portion, and described additive is selected from one or more in pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic.
In a preferred embodiment of the present invention, the content of described Gan You behenic acid ester is the 50-200 weight portion.
In a preferred embodiment of the present invention, described dry suspension compositions comprises:
The Cefpodoxime Proxetil of 100 weight portions;
121.4 the Gan You behenic acid ester of weight portion;
1142.9 the sucrose of weight portion;
2071.4 the mannitol of weight portion;
92.9 the carboxymethyl cellulose of weight portion;
28.6 the xanthan gum of weight portion;
21.4 the Herba Menthae essence of weight portion;
21.4 the aspartame of weight portion;
21.4 parts by weight of micro silica gel powder.
The present invention also provides described remarkable a kind of preparation method of improving the dry suspension compositions of Cefpodoxime Proxetil bitterness, and it may further comprise the steps:
(a) with 100 weight portion Cefpodoxime Proxetils and 25-500 weight portion Gan You behenic acid ester uniform mixing;
(b) mixture heated that step (a) is obtained makes the mixture fusion to 65-90 ℃;
(c) 30-100 mesh sieve branch was pulverized in the fused mass cooling that step (b) is obtained, and packing obtains dry suspension.
In the preferred embodiment of the present invention, also can add other additives of 500-6000 weight portion in described step (c), described additive is selected from one or more in pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic.
Compositions of the present invention can significantly be improved the bitterness of Cefpodoxime Proxetil, and the patient is easier to accept when making dry suspension compositions redispersion carry out oral administration in water, improves the clinical patients compliance, is more suitable for children.
The specific embodiment
Through a large amount of discovering, the compositions that comprises Cefpodoxime Proxetil, a certain amount of Gan You behenic acid ester can significantly be improved the bitterness of Cefpodoxime Proxetil.Therefore, can significantly improve patient's clinical application compliance.
One aspect of the present invention provides a kind of dry suspension compositions that can significantly improve the Cefpodoxime Proxetil bitterness, and it comprises:
The Cefpodoxime Proxetil of 100 weight portions;
The Gan You behenic acid ester of 25-500 weight portion.
In the present invention, used Cefpodoxime Proxetil can be commercially available conventional Cefpodoxime Proxetil, and its object lesson is the Cefpodoxime Proxetil that Aurobindo Pharma Ltd. (India I Bin Du company) produces.
In compositions of the present invention, the content of Gan You behenic acid ester should be the bitterness that can enough cover Cefpodoxime Proxetil, but the dissolution of significant prolongation Cefpodoxime Proxetil not.Therefore, the content of Gan You behenic acid ester should be the 25-500 weight portion, is preferably the 50-350 weight portion, most preferably is the 100-250 weight portion.
In the present invention, above-mentioned sweet oily behenic acid ester specifically is the commodity available from French Jia Fasai (Gatefosse) company
Figure A20081008681300041
888ATO.Described Gan You behenic acid ester records in American Pharmacopeia and European Pharmacopoeia (Glyceryl behenate), is a kind of adjuvant that pharmaceutically allows.Gan You behenic acid ester outward appearance be white to subalbous fine-powder, be that You behenic acid (22 carbon) forms with glycerine esterification, Wei the mixture of single, double nuclear triglyceride of behenic acid, major part is a diester, melting range is 69-74 ℃.In a preferred embodiment of the present invention, Gan You behenic acid ester can significantly improve the serious bitterness of Cefpodoxime Proxetil.
In compositions of the present invention, also can comprise other pharmaceutically acceptable additives.Type for described additive does not have any restriction, can be additive conventional in this area, specifically be to be selected from pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic one or more.In the present invention, the consumption for other additives does not have any restriction.In a preferred embodiment of the present invention, described content of additive is the 500-6000 weight portion.
In the present invention, do not have any restriction for the type of pharmaceutically acceptable filler, it can be a filler commonly used in this area.In a preferred embodiment of the present invention, described filler is selected from the mixture of mannitol, sucrose composition.In the present invention, do not have any restriction for the consumption of filler, it can be the conventional amount used in this area.In a preferred embodiment of the present invention, the content of described filler is the 500-6000 weight portion, is preferably the 1000-4500 weight portion, most preferably is the 1500-3000 weight portion.
In the present invention, do not have any restriction for the type of pharmaceutically acceptable suspending agent, it can be a suspending agent commonly used in this area.In a preferred embodiment of the present invention, described suspending agent is selected from the mixture of sodium carboxymethyl cellulose and xanthan gum.In the present invention, do not have any restriction for the consumption of suspending agent, it can be the conventional amount used in this area.In a preferred embodiment of the present invention, the content of described suspending agent is the 40-400 weight portion, is preferably the 60-250 weight portion, most preferably is the 80-200 weight portion.
In the present invention, do not have any restriction for the type of pharmaceutically acceptable lubricant, it can be a lubricant commonly used in this area.In a preferred embodiment of the present invention, described lubricant is selected from micropowder silica gel, magnesium stearate or its mixture.In the present invention, do not have any restriction for the consumption of lubricant, it can be the conventional amount used in this area.In a preferred embodiment of the present invention, the content of described lubricant is the 5-200 weight portion, is preferably the 10-150 weight portion, most preferably is the 15-100 weight portion.
In the present invention, do not have any restriction for the type of pharmaceutically acceptable sweeting agent, it can be a sweeting agent commonly used in this area.In a preferred embodiment of the present invention, described sweeting agent is selected from aspartame, acesulfame potassium or its mixture.In the present invention, do not have any restriction for the consumption of sweeting agent, it can be the conventional amount used in this area.In a preferred embodiment of the present invention, the content of described sweeting agent is the 5-200 weight portion, is preferably the 15-150 weight portion, most preferably is the 20-100 weight portion.
In the present invention, do not have any restriction for the type of pharmaceutically acceptable aromatic, it can be an aromatic commonly used in this area.In a preferred embodiment of the present invention, described aromatic is selected from various plant essences or its mixture.In the present invention, do not have any restriction for the consumption of aromatic, it can be the conventional amount used in this area.In a preferred embodiment of the present invention, the content of described aromatic is the 20-150 weight portion.
In the present invention, used term " pharmaceutically acceptable additive " is meant the additive of pharmaceutically acceptable reinforcement preparation performance.Examples of such additives is well-known to those skilled in the art, comprises filler, suspending agent, lubricant, sweeting agent, aromatic and other.Wherein filler is sucrose, mannitol etc.Suspending agent is sodium carboxymethyl cellulose and xanthan gum etc.Lubricant is magnesium stearate and micropowder silica gel etc.Sweeting agent is aspartame and acesulfame potassium etc.Aromatic is various plant essences etc.
The clinical use of compositions of the present invention is very simple, drinks after stirring in adding warm water or the beverage or shaking up and takes.
The present invention provides a kind of above-mentioned remarkable dry suspension method for compositions of improving the Cefpodoxime Proxetil bitterness for preparing on the other hand, and it may further comprise the steps:
(a) with 100 weight portion Cefpodoxime Proxetils and 25-500 weight portion Gan You behenic acid ester uniform mixing;
(b) mixture heated that step (a) is obtained makes the mixture fusion to 65-90 ℃;
(c) 30-100 mesh sieve branch was pulverized in the fused mass cooling that step (b) is obtained, and packing obtains dry suspension.
Also can add other additives of 500-6000 weight portion in described step (c), described additive is selected from one or more in pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic.
Further describe the present invention below by specific embodiment, but do not limit the scope of the invention.
Embodiment
1. the assay method of sedimentation volumn ratio
Carry out according to two appendix I of Chinese Pharmacopoeia version in 2005 O.The dry suspension of a packing dosage is put in the 50ml tool plug graduated cylinder, added the hot water jolting 1 minute of exerting oneself, write down the beginning height H of suspended matter 0, left standstill 3 hours, write down the final height H of suspended matter, be calculated as follows:
Sedimentation volumn ratio=H/H 0
2. Cefpodoxime Proxetil content assaying method
Measure according to two appendix V of Chinese Pharmacopoeia version in 2005 D high performance liquid chromatography.The high performance liquid chromatography chromatographic condition is: chromatographic column is ShimadzuVP-ODS (4.6mm * 250mm, 5 μ m), and mobile phase is 0.02mol/L ammonium acetate-acetonitrile (6: 4), and the detection wavelength is 260nm.During mensuration, getting the dry suspension compositions an amount of (being equivalent to cefpodoxime 25mg) of porphyrize puts in the 50ml measuring bottle, add an amount of methanol fully vibrate the dissolving Cefpodoxime Proxetil (in case of necessity can be ultrasonic), add methanol and be diluted to scale, shake up, organic filtering with microporous membrane, precision is measured subsequent filtrate 5ml and is put in the 100ml measuring bottle, add methanol and be diluted to scale, shake up, as need testing solution.Other gets the Cefpodoxime Proxetil reference substance and prepares reference substance solution with method.Get two kinds of solution, 20 μ l sample introductions respectively in high performance liquid chromatograph, calculate the content of contained Cefpodoxime Proxetil in the dry suspension compositions.
3. determination of related substances method
Measure according to two appendix V of Chinese Pharmacopoeia version in 2005 D high performance liquid chromatography.The high performance liquid chromatography chromatographic condition is: chromatographic column is Shimadzu VP-ODS (4.6mm * 250mm, 5 μ m), and mobile phase is 0.02mol/L ammonium acetate-acetonitrile (6: 4), and the detection wavelength is 260nm.During mensuration, getting the dry suspension composition powder an amount of (being equivalent to cefpodoxime 25mg) of porphyrize puts in the 50ml measuring bottle, add an amount of methanol fully vibrate the dissolving Cefpodoxime Proxetil (in case of necessity can be ultrasonic), add methanol and be diluted to scale, shake up, organic filtering with microporous membrane is got subsequent filtrate as need testing solution.Get 1ml again and put in the 100ml measuring bottle, add methanol and be diluted to scale, shake up, as need testing solution.Measure contrast solution 20 μ l and inject chromatograph of liquid, regulate instrumental sensitivity, the peak height that makes the main constituent chromatographic peak is 10~20% of a full scale.Get each 20 μ l of above-mentioned two kinds of solution again and inject chromatograph of liquid, the record chromatogram is to 2 times of main constituent chromatographic peak retention time.Calculate the related substance of dry suspension compositions.
4. dissolution determination method
According to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2005 C, second method), (glycine 54.5g and 42.6 sodium chloride are put in the 1000ml measuring bottle, add the 500ml dissolved in distilled water, add 14.2mL hydrochloric acid again with glycine-sodium chloride salt acid solution, shake up the distilled water standardize solution.Getting the 50mL thin up to 900ml, obtain the solution (in case of necessity with 10mol/L sodium hydroxide solution adjust pH) of pH 3.0 ± 0.1) 900ml is solvent, rotating speed is that per minute 75 changes, operation in accordance with the law, in the time of 45 minutes, get solution 5ml and filter, get subsequent filtrate as need testing solution; Other gets reference substance and adds in right amount and add above-mentioned dissolution medium behind the dissolve with methanol and be diluted to scale, in contrast product solution.Get above-mentioned two kinds of solution,, measure trap respectively, calculate dissolution at the wavelength place of 259nm according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2005 A).
Embodiment 1
The prescription of dry suspension 1
Preparation prescription is formed constituent content (mg) in the suspensoid of whenever being responsible for a task until it is completed
Cefpodoxime Proxetil 70mg (being equivalent to cefpodoxime 50mg)
Gan You behenic acid ester (
Figure A20081008681300041
888ATO) 85mg
Mannitol 1450mg
Sucrose 800mg
Sodium carboxymethyl cellulose 65mg
Xanthan gum 20mg
Herba Menthae essence 15mg
Aspartame 15mg
Micropowder silica gel 15mg
Preparation method: with 80 mesh sieves sieve respectively Cefpodoxime Proxetil (Aurobindo Pharma Ltd. India I Bin Du company) and
Figure A20081008681300041
888 ATO (French Jia Fasai Gattefosse S.A) are with they mix homogeneously.Mixture is placed 80-85 ℃ of constant temperature oven heating 10-15 minute, make Cefpodoxime Proxetil and
Figure A20081008681300041
888 ATO melt jointly.Then described fused mixture is cooled to room temperature, then pulverizes, cross 60 mesh sieve branches.In the fine powder of screening gained, add sucrose (Guangxi Liu Xing sugar industry company limited), mannitol (Qingdao Mingyue Marine Alga Group Corp., Ltd.), sodium carboxymethyl cellulose (Guangzhou Jinzhujiang Chemical Co., Ltd.), xanthan gum (Shandong Zhong Xuan limited company), aspartame (U.S. Niu Te company), Herba Menthae essence (Kunming Fen Meiyi spice company limited), micropowder silica gel (German Wacker).With said mixture with 40 mesh sieve mix homogeneously after, divide packing, every bag packing 2.535g.
Adopt embodiment 1 preparation to Cefpodoxime proxetil suspension carry out quality investigation, the result is as follows:
Project The sedimentation volumn ratio Dissolution Related substance Content
The result >0.9 85.6% 1.86% 98.96%
The comparative example
Prepare comparative example 1 with the method identical with embodiment 1, difference only is to have omitted
Figure A20081008681300041
888 ATO, its concrete component and content see the following form 1.
Comparative example 2 component and content thereof and embodiment 1 are identical, specifically referring to table 1, difference only be in preparation dry suspension compositions, to have omitted with Cefpodoxime Proxetil and Gan You behenic acid ester (
Figure A20081008681300041
888 ATO) step of melting mixing, but each component is directly mixed.
Table 1 comparative example 1 and 2
Figure A20081008681300083
Standards of grading:
Give 10 healthy volunteers respectively with the Cefpodoxime proxetil suspension mixture that makes among the foregoing description and the comparative example, allow it take after, record experimenter mouthfeel, and mark according to following standard, the result sees table 2.
Estimate the standard of bitterness:
0: do not have bitterness.
1: almost do not have bitterness, need careful sensation that bitterness is just arranged;
2: bitterness is very light;
3: bitterness is arranged, but be not very bitter;
4: very bitter;
The result that table 2 is estimated
Embodiment 1 The comparative example 1 The comparative example 2
Bitterness 1 4 4
Cefpodoxime proxetil suspension composition of the present invention is used Gan You behenic acid ester, adopts the fusion process for cooling significantly to improve the bitterness of Cefpodoxime Proxetil, has improved the compliance of patient's clinical application.

Claims (5)

1. Cefpodoxime proxetil suspension composition is characterized in that it comprises:
The Cefpodoxime Proxetil of 100 weight portions;
The Tridocosanoin of 25-500 weight portion,
Described compositions is prepared by following method, said method comprising the steps of:
(a) with 100 weight portion Cefpodoxime Proxetils and 25-500 weight portion Gan You behenic acid ester uniform mixing;
(b) mixture heated that step (a) is obtained makes the mixture fusion to 65-90 ℃;
(c) 30-100 mesh sieve branch was pulverized in the fused mass cooling that step (b) is obtained, and packing obtains dry suspension.
2. Cefpodoxime proxetil suspension composition as claimed in claim 1, it is characterized in that, it also comprises the additive of 500-6000 weight portion, and described additive is selected from one or more in pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic.
3. Cefpodoxime proxetil suspension composition as claimed in claim 1 is characterized in that it comprises:
The Cefpodoxime Proxetil of 100 weight portions;
121.4 the Gan You behenic acid ester of weight portion;
1142.9 the sucrose of weight portion;
2071.4 the mannitol of weight portion;
92.9 the carboxymethyl cellulose of weight portion;
28.6 the xanthan gum of weight portion;
21.4 the Herba Menthae essence of weight portion;
21.4 the aspartame of weight portion;
21.4 parts by weight of micro silica gel powder.
4. dry suspension preparation of compositions method as claimed in claim 1, it may further comprise the steps:
(a) with 100 weight portion Cefpodoxime Proxetils and 25-500 weight portion Gan You behenic acid ester uniform mixing;
(b) mixture heated that step (a) is obtained makes the mixture fusion to 65-90 ℃;
(c) 30-100 mesh sieve branch was pulverized in the fused mass cooling that step (b) is obtained, and packing obtains dry suspension.
5. method as claimed in claim 4, it is characterized in that, also can add other additives of 500-6000 weight portion in described step (c), described additive is selected from one or more in pharmaceutically acceptable filler, pharmaceutically acceptable suspending agent, pharmaceutically acceptable lubricant, pharmaceutically acceptable sweeting agent and the pharmaceutically acceptable aromatic.
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Cited By (8)

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CN102327217A (en) * 2011-07-14 2012-01-25 海南美大制药有限公司 Solid cefpodoxime proxetil liposome preparation
CN102440960A (en) * 2011-09-01 2012-05-09 山东鲁抗医药股份有限公司 Pharmaceutical composition of cefuroxime axetil for suspension and preparation method thereof
CN102525948A (en) * 2012-01-17 2012-07-04 山东罗欣药业股份有限公司 Dry suspension of cefpodoxime proxetil composition and preparation method thereof
CN103230367A (en) * 2013-05-07 2013-08-07 山东罗欣药业股份有限公司 Cefpodoxime proxetil composition dry suspension and preparation method thereof
CN103275102A (en) * 2013-05-28 2013-09-04 四川省惠达药业有限公司 Cefpodoxime proxetil compound as well as preparation method and medicinal composition thereof
CN106692068A (en) * 2017-01-16 2017-05-24 中国药科大学 Dry suspension for improving dissolution
CN107625754A (en) * 2016-07-15 2018-01-26 北京科信必成医药科技发展有限公司 A kind of Cefpodoxime Proxetil taste masked particle and preparation method thereof
CN110437259A (en) * 2019-08-14 2019-11-12 中国药科大学 Cefpodoxime Proxetil naringenin is total to amorphous substance and preparation method thereof

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ES2248521T3 (en) * 2001-02-27 2006-03-16 Ranbaxy Laboratories, Ltd. ORAL PHARMACEUTICAL COMPOSITION OF CEFPODOXIMA PROXETILO.
CN1235576C (en) * 2002-05-16 2006-01-11 中国人民解放军第二军医大学 Slow-released dosage form of sodium ferulate and preparation process thereof
WO2004105728A2 (en) * 2003-05-27 2004-12-09 Ranbaxy Laboratories Limited Solid dispersions of cefpodoxime proxetil and processes for their preparation

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CN102327217A (en) * 2011-07-14 2012-01-25 海南美大制药有限公司 Solid cefpodoxime proxetil liposome preparation
CN102327217B (en) * 2011-07-14 2012-11-21 海南美大制药有限公司 Solid cefpodoxime proxetil liposome preparation
CN102440960A (en) * 2011-09-01 2012-05-09 山东鲁抗医药股份有限公司 Pharmaceutical composition of cefuroxime axetil for suspension and preparation method thereof
CN102525948A (en) * 2012-01-17 2012-07-04 山东罗欣药业股份有限公司 Dry suspension of cefpodoxime proxetil composition and preparation method thereof
CN103230367A (en) * 2013-05-07 2013-08-07 山东罗欣药业股份有限公司 Cefpodoxime proxetil composition dry suspension and preparation method thereof
CN103230367B (en) * 2013-05-07 2014-11-12 山东罗欣药业集团股份有限公司 Cefpodoxime proxetil composition dry suspension and preparation method thereof
CN103275102B (en) * 2013-05-28 2014-07-09 四川省惠达药业有限公司 Cefpodoxime proxetil compound as well as preparation method and medicinal composition thereof
CN103275102A (en) * 2013-05-28 2013-09-04 四川省惠达药业有限公司 Cefpodoxime proxetil compound as well as preparation method and medicinal composition thereof
CN107625754A (en) * 2016-07-15 2018-01-26 北京科信必成医药科技发展有限公司 A kind of Cefpodoxime Proxetil taste masked particle and preparation method thereof
CN107625754B (en) * 2016-07-15 2022-07-01 北京科信必成医药科技发展有限公司 Cefpodoxime proxetil taste masking particles and preparation method thereof
CN106692068A (en) * 2017-01-16 2017-05-24 中国药科大学 Dry suspension for improving dissolution
CN110437259A (en) * 2019-08-14 2019-11-12 中国药科大学 Cefpodoxime Proxetil naringenin is total to amorphous substance and preparation method thereof
CN110437259B (en) * 2019-08-14 2021-12-07 中国药科大学 Cefpodoxime proxetil naringenin amorphous substance and preparation method thereof

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