CN117503701A - Levofloxacin oral suspension preparation and preparation method thereof - Google Patents

Levofloxacin oral suspension preparation and preparation method thereof Download PDF

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CN117503701A
CN117503701A CN202311677057.0A CN202311677057A CN117503701A CN 117503701 A CN117503701 A CN 117503701A CN 202311677057 A CN202311677057 A CN 202311677057A CN 117503701 A CN117503701 A CN 117503701A
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levofloxacin
oral suspension
preparation
sweetener
suspension formulation
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胡关容
沈梦妮
杨勇
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Stande Pharmaceutical R&d Jiangsu Co ltd
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Stande Pharmaceutical R&d Jiangsu Co ltd
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

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Abstract

The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a levofloxacin oral suspension preparation and a preparation manufacturing method thereof. The suspension preparation comprises 100.0mg/ml of levofloxacin, 4.7mg/ml to 5.3mg/ml of suspending agent, 200mg/ml to 400mg/ml of sweetener, 1.8mg/ml to 2.2mg/ml of pH regulator, 0.8mg/ml to 1.0mg/ml of opacifier, 0 to 0.5mg/ml of preservative, 0 to 3mg/ml of aromatic and 0 to 0.6mg/ml of colorant. The components are mutually matched to form uniform suspension, the taste and sweetness are proper, the levofloxacin serving as an active ingredient is uniformly dispersed in the suspension, the administration dosage can be accurately controlled, excessive treatment or insufficient treatment is avoided, the fruit taste favored by children can be prepared, the psychological of the children is met, and the administration difficulty of infants is reduced. Solves the problem of poor medication compliance of the existing medicines sold in the market to special groups, so as to ensure that the patients achieve the expected effect in the treatment process. The preparation manufacturing method provided by the invention has the advantages of simple processing and manufacturing process, short flow, easily available raw material sources, low cost, suitability for commercial production and wide market prospect.

Description

Levofloxacin oral suspension preparation and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a levofloxacin oral suspension preparation and a preparation manufacturing method thereof.
Background
The levofloxacin is a third-generation fluoroquinolone broad-spectrum antibacterial agent, the main action mechanism is to block the activity of DNA helicase, the intensity of the levofloxacin is 2 times that of the ofloxacin, the occurrence rate of adverse reaction is low, the toxic and side effects are greatly reduced, and the levofloxacin is one of the best varieties of the existing quinolone medicines. Levofloxacin has a broad-spectrum antibacterial effect on gram-positive bacteria and gram-negative bacteria including anaerobic bacteria, and shows a strong antibacterial activity on staphylococcus, enteritis, streptococcus pyogenes, streptococcus hemolyticus, enterococcus, and enterobacteria including escherichia coli, klebsiella, serratia, proteus, glucose non-fermented gram-negative bacteria including pseudomonas aeruginosa, haemophilus influenzae, gonococcus, and the like.
The levofloxacin is in the form of tablets, capsules and injection in the market at present, has poor medicine taking compliance for children, old people and dysphagia patients, and particularly has high risk for children patients due to intramuscular injection or intravenous drip, high operation difficulty and easy crying and anxiety of children patients, and is extremely incoordination. Meanwhile, the levofloxacin raw material has strong bitter taste, and common granules used by children are difficult to mask the bad taste of the levofloxacin. Therefore, there is a need to develop a dosage form that addresses the problem of poor patient compliance and improves the bioavailability of levofloxacin.
The information disclosed in this background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person of ordinary skill in the art.
Disclosure of Invention
The invention aims to solve the problems, and aims to provide the levofloxacin oral suspension preparation and the preparation manufacturing method thereof, which not only can overcome the defects and solve the problem of poor medication compliance of patients, but also can improve the bioavailability of the levofloxacin, and have positive significance for ensuring the safety of clinical medication.
The invention provides a levofloxacin oral suspension preparation, which has the characteristics that the levofloxacin oral suspension preparation comprises the following components:
levofloxacin, 100.0mg/ml;
suspending agent, 4.7 mg/ml-5.3 mg/ml;
sweetener, 200 mg/ml-400 mg/ml;
pH regulator, 1.8 mg/ml-2.2 mg/ml;
opacifying agent, 0.8 mg/ml-1.0 mg/ml;
preservative, 0-0.5 mg/ml;
0-3 mg/ml of aromatic;
0 to 0.6mg/ml of coloring agent.
In the invention, the preservative is preferably 0.3mg/ml to 0.5mg/ml; the aromatic agent is preferably 2mg/ml to 3mg/ml; the colorant is preferably 0.5mg/ml to 0.6mg/ml.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein the suspending agent is one or more of xanthan gum, gelatin, acacia, carrageenan, agar, povidone, polyvinyl alcohol, maltitol, xylitol, glucose, fructose, sorbitol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, and sodium carboxymethyl cellulose.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein the sweetener is one or more of sucrose, sorbitol, xylitol, glucose, fructose, maltitol, acesulfame potassium, aspartame, saccharin sodium, liquid maltitol, and sucralose.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein the pH regulator is one or more of citric acid, sodium citrate, sodium phosphate and potassium citrate.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein the preservative is one or more of sodium benzoate, benzoic acid, ethylene diamine tetraacetic acid, sorbic acid, bronopol, butylparaben, methyl paraben, ethyl paraben and propyl paraben, and the aromatic is one or more of artificial strawberry spice, margarine spice, vanilla, cherry and raspberry.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein the opacifier is titanium dioxide and the colorant is carmine.
The levofloxacin oral suspension preparation provided by the invention can also have the following characteristics: wherein, the wetting agent in the levofloxacin oral suspension preparation is any one or more of water, propylene glycol and polyethylene glycol.
The invention also provides a preparation method of the levofloxacin oral suspension preparation, which has the characteristics that the preparation method comprises the following steps:
step S1, adding a preservative, a pH regulator, a wetting agent, a opacifier, a first sweetener and levofloxacin into the wetting agent, and stirring until the mixture is dissolved to obtain a suspension A;
and S2, adding a suspending agent into the suspension A, shearing at a high speed to form a uniform thick suspension system, then adding a second sweetener, a flavoring agent and a coloring agent, continuing shearing at a high speed to uniformly disperse, adjusting the pH value to 5.2-5.8 by using a pH regulator, adding a wetting agent to a preset amount, and continuing shearing at a high speed to uniformly disperse to obtain the levofloxacin oral suspension preparation.
In the method for preparing the levofloxacin oral suspension preparation provided by the invention, the preparation method can also have the following characteristics: wherein the first sweetener is sucralose, the second sweetener is liquid maltitol,
in step S2, the suspending agent comprises hydroxypropyl cellulose and xanthan gum, wherein the hydroxypropyl cellulose is added into the xanthan gum, sheared at a high speed to dissolve the hydroxypropyl cellulose, and then added into the suspension a.
Effects and effects of the invention
The levofloxacin oral suspension preparation provided by the invention has the advantages that all the components are mutually matched to form uniform suspension, and the levofloxacin oral suspension preparation is suitable for infants in taste and sweetness and is more suitable for taking medicines. In addition, the oral suspension is uniformly shaken before use, the medicine is uniformly dispersed in the system, the stability is strong, the oral suspension can be diluted, the oral suspension can be taken after being added into drinking water, and the drug effect is not affected by adding sweetening agents such as sucrose and the like. The oral suspension overcomes the problem that the tablet and the capsule are difficult to take due to throat stenosis of infants, levofloxacin serving as an active ingredient is uniformly dispersed in the suspension, the taking dosage can be accurately controlled, excessive treatment or insufficient treatment is avoided, and the oral suspension can be prepared into the favorite fruit taste of the infants, caters to the psychological of the infants and reduces the difficulty of taking the infants. Therefore, the levofloxacin oral suspension preparation can be mainly used for special crowds, such as children, old people, dysphagia, patients in certain special environments and the like, especially patients who are not willing to take active medicines or do not take medicines in a matched mode, and solves the problem that the medicines sold in the prior market have poor medication compliance for the patients, so as to ensure that the patients achieve the expected effect in the treatment process.
The preparation method provided by the invention has the advantages of simple processing and manufacturing process, short flow, readily available raw material sources, low cost, good uniformity of the obtained suspension, convenience in carrying and administration, consistent quality and curative effect with those of the levofloxacin tablet, suitability for commercial production and wide market prospect.
Drawings
FIG. 1 is a graph showing the saturation solubility of levofloxacin drug substance in screening example 1 of the present invention;
FIG. 2 is a dissolution profile of the homemade oral suspension and colastun in test example 1 of the present invention.
Detailed Description
In order to make the technical means, creation characteristics, achievement purposes and effects of the present invention easy to understand, the present invention's levofloxacin oral suspension formulation and the formulation manufacturing method will be specifically described below with reference to examples and drawings.
Unless otherwise indicated, reagents and pharmaceuticals for use in the present invention are commercially available. The purified water is the purified water specified in Chinese pharmacopoeia.
The invention provides a levofloxacin oral suspension preparation, which comprises the following components:
levofloxacin, 100.0mg/ml;
suspending agent, 4.7 mg/ml-5.3 mg/ml;
sweetener, 200 mg/ml-400 mg/ml;
pH regulator, 1.8 mg/ml-2.2 mg/ml;
opacifying agent, 0.8 mg/ml-1.0 mg/ml;
preservative, 0-0.5 mg/ml;
0-3 mg/ml of aromatic;
0 to 0.6mg/ml of coloring agent.
Preferably, the preservative is 0.3mg/ml to 0.5mg/ml; fragrance, 2 mg/ml-3 mg/ml; colorant, 0.5 mg/ml-0.6 mg/ml.
Among the above raw materials, the suspending agent is selected from one or more of xanthan gum, gelatin, acacia, carrageenan, agar, povidone, polyvinyl alcohol, maltitol, xylitol, glucose, fructose, sorbitol, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose.
The sweetener is selected from one or more of sucrose, sorbitol, xylitol, glucose, fructose, maltitol, acesulfame potassium, aspartame, saccharin sodium, liquid maltitol, and sucralose.
The pH regulator is one or more of citric acid, sodium citrate, sodium phosphate and potassium citrate.
The antiseptic is selected from one or more of sodium benzoate, benzoic acid, tetra sodium ethylenediamine tetraacetate, sorbic acid, bromonitropropylene glycol, butylparaben, methyl paraben, ethyl paraben, and propyl paraben.
The flavoring agent is selected from one or more of artificial strawberry flavor, artificial butter flavor, vanilla, cherry, and raspberry. The opacifying agent is titanium dioxide, and the coloring agent is carmine.
The wetting agent in the levofloxacin oral suspension is any one or more of water, propylene glycol and polyethylene glycol.
The levofloxacin oral suspension preparation is prepared by the following method, and specifically comprises the following steps:
step S1, adding a preservative, a pH regulator, a wetting agent, a opacifier, a first sweetener and levofloxacin into the wetting agent, and stirring until the mixture is dissolved to obtain a suspension A;
and S2, adding a suspending agent into the suspension A, shearing at a high speed to form a uniform thick suspension system, then adding a second sweetener, a flavoring agent and a coloring agent, continuing shearing at a high speed to uniformly disperse, adjusting the pH value to 5.2-5.8 by using a pH regulator, adding a wetting agent to a preset amount, and continuing shearing at a high speed to uniformly disperse to obtain the levofloxacin oral suspension preparation.
The first sweetener is sucralose, and the second sweetener is liquid maltitol.
In step S2, the suspending agent comprises hydroxypropyl cellulose and xanthan gum, wherein the hydroxypropyl cellulose is added into the xanthan gum, sheared at a high speed to dissolve the hydroxypropyl cellulose, and then added into the suspension a.
< screening example 1>
The screening example tests the saturated solubility of levofloxacin bulk drug in solutions of different pH values to select an appropriate solution for dissolving the levofloxacin bulk drug.
The levofloxacin crude drug was used as a solute, sodium acetate buffers at pH4.0 and pH5.0, potassium phosphate buffers at pH6.0, pH7.0 and pH8.0, and boric acid-potassium chloride buffer at pH9.0 were used as solvents at 25℃and were shaken in a shaker for 48 hours, and samples were taken for content detection. The content is determined according to high performance liquid chromatography (China pharmacopoeia 2020 edition four general rules 0512), and is specifically as follows:
each test solution: the above samples were measured precisely and quantitatively diluted with water to a solution containing about 0.08mg of levofloxacin per 1ml, respectively.
Control solution: taking a proper amount of pure levofloxacin, precisely weighing, dissolving with water and quantitatively diluting to prepare a solution containing 0.08mg of levofloxacin in each 1 ml.
Chromatographic conditions: octadecylsilane chemically bonded silica is used as a filler; ammonium acetate sodium perchlorate solution (4.0 g of ammonium acetate and 7.0g of sodium perchlorate are taken, 1300ml of water is added to dissolve, and phosphoric acid is used for adjusting the pH value to 2.2) -acetonitrile (85:15) is used as a mobile phase; the detection wavelength was 294nm and the sample volume was 10. Mu.l.
The results are shown in Table 1.
TABLE 1 saturation solubility summary table of levofloxacin bulk drug
The results of table 1 can form figure 1 in the form of a curve.
As can be seen from FIG. 1 and Table 1, the saturated solubility of levofloxacin was 22.11mg/ml to 38.63mg in the range of pH4.0 to pH 9.0. The levofloxacin product exists in a partially suspended state.
Example 1 ]
100ml of levofloxacin oral suspension preparation is prepared by the preparation method, and the ingredients are as follows in table 2:
table 2 composition of oral suspension in example 1
Material mg/ml
Levofloxacin 5
Sodium benzoate 0.2
Titanium dioxide 0.1
Hydroxypropyl cellulose 2.0
Glycerol 10
Citric acid 1
Sodium citrate 2
Sucralose 30
Liquid maltitol 25
Xanthan gum 10
Strawberry essence 1
Carmine 0.2
Purified water Allowance of
Test example 1 ]
The test example uses the levofloxacin oral suspension preparation prepared in the example 1 and the levofloxacin tablet @Lot number: BS001G 1) for dissolution detection, the specific experimental procedure is as follows:
the dissolution curve of the levofloxacin oral suspension and the ofloxacin tablet is detected by using a paddle method in a method for measuring the dissolution rate and the release rate of the ofloxacin oral suspension and the ofloxacin tablet according to the rule 0931 of the 2020 edition of Chinese pharmacopoeia, and the specific method is as follows:
the experimental results are shown in Table 3.
TABLE 3 oral suspension and tablet dissolution results
The results of table 3 can form fig. 2 in the form of a curve.
As can be seen from fig. 2 and table 3, the in vitro dissolution rate of the self-made oral suspension is slightly faster than that of the tablet, which is beneficial to rapid drug release.
Test example 2 ]
The test example uses levofloxacin tablets for comparison and tests the stability of levofloxacin oral suspension. Levofloxacin tabletAn oral suspension of levofloxacin was prepared from example 1.
The initial state is represented by 0 days, the sample discharge amount of the suspension under each investigation condition is 10ml of levofloxacin oral suspension, and similarly, the sample discharge amount of the levofloxacin tablet under each investigation condition is5 tablets.
The investigation conditions are respectively as follows: light-shielding inspection at a high temperature of 40 ℃ and a temperature of 60 ℃ for 30 days; at a total illuminance of not less than 1.2X10 6 Lux.hr, and near ultraviolet energy not lower than 200w.hr/m 2 Light is used for investigation for 10 days; accelerated investigation was performed at 40℃under 75% RH.+ -. 5% RH for 3 months and 6 months. When the oral suspension is examined for 10 days under the illumination condition, the self-made oral suspension is respectively packaged by a brown bottle and a transparent bottle, and the rest conditions are that the oral suspension is packaged by the transparent bottle. The levofloxacin tablet is exposed. The results are shown in tables 4 and 5.
Table 4 stability data for levofloxacin oral suspension formulations
TABLE 5 stability data for levofloxacin tablets
In tables 4 and 5, the content was measured by high performance liquid chromatography (chinese pharmacopoeia 2020 edition, fourth edition, general rule 0512), and specifically, the content was as follows:
each test solution: the sample was measured precisely and diluted quantitatively with water to a solution of about 0.08mg of levofloxacin per 1 ml.
Control solution: taking a proper amount of pure levofloxacin, precisely weighing, dissolving with water and quantitatively diluting to prepare a solution containing 0.08mg of levofloxacin in each 1 ml.
Chromatographic conditions: octadecylsilane chemically bonded silica is used as a filler; ammonium acetate sodium perchlorate solution (4.0 g of ammonium acetate and 7.0g of sodium perchlorate are taken, 1300ml of water is added to dissolve, and phosphoric acid is used for adjusting the pH value to 2.2) -acetonitrile (85:15) is used as a mobile phase; the detection wavelength was 294nm and the sample volume was 10. Mu.l.
The sedimentation volume ratio detection method specifically comprises the following steps:
50ml of the sample was measured with a plug cylinder, sealed, and shaken vigorously for 1 minute, and the starting height H of the suspension was recorded 0 Standing for 3 hours, recording the final height H of the suspension, and calculating according to the following formula: sedimentation volume ratio = H/H 0 。
The related substances are measured according to high performance liquid chromatography (China pharmacopoeia 2020 edition four general rules 0512), and the specific steps are as follows:
each test solution: a proper amount of the sample is precisely measured, and the sample is respectively quantitatively diluted by water to prepare a solution containing 0.4mg of levofloxacin in each 1 ml.
Control solution: accurately weighing right amount of pure levofloxacin, dissolving with water and quantitatively diluting to obtain solution containing 0.8 mug of levofloxacin in each 1 ml.
Chromatographic conditions: octadecylsilane chemically bonded silicse:Sup>A is used as filler (YMC-Pack ODS-A, 4.0mm. Times.150 mm,3.0 μm or column with equivalent performance); gradient elution was performed using acetonitrile-buffer (16:84) as mobile phase A and acetonitrile-methanol-buffer (30:20:50) as mobile phase B, as follows; the flow rate is 1.0ml per minute; column temperature is 38 ℃; the detection wavelength is 280nm; the sample volume was 10. Mu.l. The buffer solution is prepared as follows: 3.08g of ammonium acetate and 8.43g of sodium perchlorate are taken up in 1000ml of water and dissolved, and the pH is adjusted to 2.2 with phosphoric acid.
In tables 4 and 5, the chemical names and structural formulas of the impurities are shown in Table 6.
TABLE 6 impurity names and Structure
From tables 4 and 5, the levofloxacin oral suspension preparation has no obvious changes in pH value, content, sedimentation volume ratio and related substances under the conditions of high temperature, illumination and acceleration, and the quality of the oral suspension is not obviously different from that of the levofloxacin tablet.
Effects and effects of the examples
The levofloxacin oral suspension preparation provided by the embodiment of the invention has the advantages that all the components are mutually matched to form uniform pink suspension, the taste and sweetness are proper, the strawberry fragrance is provided, and the preparation is more suitable for infants to take medicine. The oral suspension of the formula is uniformly shaken before use, the medicine is uniformly dispersed in the system, the stability is strong, the medicine can be diluted, the medicine can be taken after being added into drinking water, and the medicine effect is not affected by adding sweetening agents such as sucrose and the like. The oral suspension overcomes the problem that tablets and capsules are difficult to take due to throat stenosis of infants, levofloxacin serving as an active ingredient is uniformly dispersed in the suspension, the taking dosage can be accurately controlled, excessive treatment or insufficient treatment is avoided, and the oral suspension is prepared into the favorite fruit taste of the infants, caters to the psychological of the infants, and reduces the difficulty of taking the infants. The levofloxacin oral suspension preparation provided by the embodiment is mainly used for special crowds, such as children, old people, dysphagia, patients in certain special environments and the like, particularly patients who are not willing to take medicines actively or do not take medicines together, and solves the problem that the medicines sold in the prior market have poor medication compliance for the patients, so as to ensure that the patients achieve the expected effect in the treatment process.
The preparation method provided by the embodiment of the invention has the advantages of simple processing and manufacturing process, short flow, easily available raw material sources, low cost, good uniformity of the obtained suspension, convenience for carrying and administration, consistent quality and curative effect with those of the levofloxacin tablet, suitability for commercial production and wide market prospect.
The above embodiments are preferred examples of the present invention, and are not intended to limit the scope of the present invention.

Claims (10)

1. An oral suspension formulation of levofloxacin, comprising the following components:
levofloxacin, 100.0mg/ml;
suspending agent, 4.7 mg/ml-5.3 mg/ml;
sweetener, 200 mg/ml-400 mg/ml;
pH regulator, 1.8 mg/ml-2.2 mg/ml;
opacifying agent, 0.8 mg/ml-1.0 mg/ml;
preservative, 0-0.5 mg/ml;
0-3 mg/ml of aromatic;
0 to 0.6mg/ml of coloring agent.
2. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein, the preservative is 0.3mg/ml to 0.5mg/ml;
fragrance, 2 mg/ml-3 mg/ml;
0.5mg/ml to 0.6mg/ml of colorant.
3. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the suspending agent is one or more of xanthan gum, gelatin, acacia, carrageenan, agar, povidone, polyvinyl alcohol, maltitol, xylitol, glucose, fructose, sorbitol, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose.
4. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the sweetener is one or more of sucrose, sorbitol, xylitol, glucose, fructose, maltitol, acesulfame potassium, aspartame, saccharin sodium, liquid maltitol and sucralose.
5. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the pH regulator is one or more of citric acid, sodium citrate, sodium phosphate and potassium citrate.
6. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the preservative is any one or more of sodium benzoate, benzoic acid, tetra sodium ethylene diamine tetraacetate, sorbic acid, bromonitropropylene glycol, butylparaben, methyl paraben, ethyl paraben and propyl paraben,
the flavoring agent is one or more of artificial strawberry flavor, margarine flavor, vanilla, cherry, and raspberry.
7. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the opacifier is titanium dioxide and the colorant is carmine.
8. The oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein, the wetting agent in the levofloxacin oral suspension preparation is any one or more of water, propylene glycol and polyethylene glycol.
9. A method of manufacturing an oral suspension formulation of levofloxacin according to any one of claims 1 to 8, comprising the steps of:
step S1, adding a preservative, a pH regulator, a wetting agent, a opacifier, a first sweetener and levofloxacin into the wetting agent, and stirring until the mixture is dissolved to obtain a suspension A;
and S2, adding a suspending agent into the suspension A, shearing at a high speed to form a uniform thick suspension system, adding a second sweetener, a fragrance and a colorant, continuing shearing at a high speed to uniformly disperse, adjusting the pH value to 5.2-5.8 by using a pH regulator, adding a wetting agent to a preset amount, and continuing shearing at a high speed to uniformly disperse to obtain the levofloxacin oral suspension preparation.
10. The method of manufacturing an oral suspension formulation of levofloxacin according to claim 1, characterized in that:
wherein the first sweetener is sucralose, the second sweetener is liquid maltitol,
in step S2, the suspending agent includes hydroxypropyl cellulose and xanthan gum, wherein the hydroxypropyl cellulose is added into the xanthan gum, and then added into the suspension a after being sheared at a high speed to dissolve.
CN202311677057.0A 2023-12-08 2023-12-08 Levofloxacin oral suspension preparation and preparation method thereof Pending CN117503701A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1360504A (en) * 1999-07-09 2002-07-24 奥索-麦克尼尔药品公司 Taste masked pharmaceutical liquid formulations
US20030032600A1 (en) * 2001-03-05 2003-02-13 Ulrich Stephen A. Taste masked liquid pharmaceutical compositions
WO2017151664A1 (en) * 2016-02-29 2017-09-08 Belmont University Pharmaceutical compositions for fluoroquinolone drug delivery
CN111491639A (en) * 2017-09-20 2020-08-04 异位性医疗有限责任公司 Compositions and methods for treating and ameliorating respiratory conditions and mucosal inflammation
JP2021187767A (en) * 2020-05-28 2021-12-13 日医工株式会社 Easy-to-take and stable pharmaceutical composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1360504A (en) * 1999-07-09 2002-07-24 奥索-麦克尼尔药品公司 Taste masked pharmaceutical liquid formulations
US20030032600A1 (en) * 2001-03-05 2003-02-13 Ulrich Stephen A. Taste masked liquid pharmaceutical compositions
WO2017151664A1 (en) * 2016-02-29 2017-09-08 Belmont University Pharmaceutical compositions for fluoroquinolone drug delivery
CN111491639A (en) * 2017-09-20 2020-08-04 异位性医疗有限责任公司 Compositions and methods for treating and ameliorating respiratory conditions and mucosal inflammation
JP2021187767A (en) * 2020-05-28 2021-12-13 日医工株式会社 Easy-to-take and stable pharmaceutical composition

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