CN113350297A - Tilmicosin dry suspension and preparation method thereof - Google Patents
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Abstract
The invention provides tilmicosin dry suspension and a preparation method thereof, and relates to the technical field of veterinary drugs, wherein each 100 parts of the dry suspension comprise the following raw materials by weight: 10-20 parts of tilmicosin, 14-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 1-5 parts of carbomer, 1-5 parts of poloxamer, 5-10 parts of carboxymethyl starch sodium, 0.2-0.5 part of silicon dioxide, 0.1-0.2 part of a phagostimulant and 34.3-68.7 parts of glucose. The sodium carboxymethyl starch and the silicon dioxide are added as the disintegrating agent, so that the sodium carboxymethyl starch and the silicon dioxide can be uniformly dispersed without strong shaking or stirring in clinical application. The tilmicosin dry suspension has good dispersibility in water, can act on livestock and poultry through drinking water administration, and is suitable for being used in large-scale farms; and the palatability is good, and the feeding of animals is not influenced by the feeding of the animals after the feed is mixed and the drinking water is used. The product of the invention has good stability, strong production process operability and good development prospect.
Description
Technical Field
The invention relates to the technical field of veterinary drugs, and particularly relates to tilmicosin and a preparation method thereof.
Background
Tilmicosin is a semisynthetic macrolide antibiotic used for livestock and poultry, and similar to other macrolides, tilmicosin has the characteristics of rapid absorption, low bacteriostatic concentration, long half-life and the like, and has high concentration in lungs and milk. Tilmicosin is used for treating pneumonia caused by pasteurella multocida, actinobacillus pleuropneumoniae and pasteurella hemolyticus, has a good treatment effect on mycoplasma, streptococcus and staphylococcus aureus infected by pigs, cattle and sheep, and is also used for preventing and treating mastitis of ruminants and respiratory infection of poultry caused by susceptible organisms.
The incidence of infectious diseases in livestock and poultry continues to rise worldwide, causing significant economic losses to the aquaculture industry. Such as mastitis caused by cow infection, respiratory diseases of chicken caused by mycoplasma gallisepticum and mycoplasma synoviae, and respiratory diseases of pig caused by gram-negative bacillus parasuis Haemophilus. Tilmicosin has a strong antibacterial effect, can improve the immunity of an animal body, has no cross resistance with other clinically common antibiotics, and becomes a first choice medicament for antibiosis in recent years. The tilmicosin dosage form recorded in the section of the 'Chinese veterinary pharmacopoeia' of the 2015 edition comprises: injections, solutions and premixes; however, the tilmicosin injection has high toxicity, is only suitable for cattle and is inconvenient for group use, and the tilmicosin premix and the tilmicosin solution have serious bitter taste, so that the direct application to animals with sensitive taste can cause the reduction of food intake and cause the limitation of the clinical application; the tilmicosin premix has poor water solubility and cannot be taken by drinking water. The clinically applied tilmicosin phosphate solution has lower titer and bioavailability. High doses of tilmicosin may improve clinical efficacy, but there is a risk of acute cardiotoxicity because the severity of tilmicosin toxic effects is dose dependent.
The dry suspension is one of internal suspensions, and refers to a suspension preparation for internal administration, which is prepared by processing an insoluble solid raw material medicament and proper auxiliary materials through a process and uniformly dispersing the insoluble solid raw material medicament and the proper auxiliary materials in a liquid medium. The dry suspension can improve the stability of the suspension in the storage and transportation processes, and can be used for mixing materials and drinking water in clinical application. When the medicine is taken by drinking water, the medicine can be uniformly dispersed in water in the form of micro powder, and has higher bioavailability. Because the animal administration is group administration, the dry suspension can not be dispersed by strong shaking in clinical application, and the administration can not be finished in a short time, so the dry suspension for animals has higher requirements on dispersibility and sedimentation.
Therefore, based on the research background, it is necessary to develop a new tilmicosin preparation which has the advantages of wide application range, convenient administration, quick acting, small toxic and side effects, stability, low production cost and simple and feasible process. Therefore, it is necessary to develop a new preparation with high safety, good bioavailability, wide application range and low production cost.
Disclosure of Invention
Technical problem to be solved
Aiming at the defects of the prior art, the invention provides the tilmicosin dry suspension and the preparation method thereof, wherein the tilmicosin dry suspension has the advantages of high safety, good bioavailability, wide application range, convenient administration and low production cost.
(II) technical scheme
In order to achieve the purpose, the invention is realized by the following technical scheme:
on one hand, the invention provides tilmicosin dry suspension, and each 100 parts of the dry suspension comprise the following raw materials by weight: 10-20 parts of tilmicosin, 14-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 1-5 parts of carbomer, 1-5 parts of poloxamer, 5-10 parts of carboxymethyl starch sodium, 0.2-0.5 part of silicon dioxide, 0.1-0.2 part of a phagostimulant and 34.3-68.7 parts of glucose.
Further, as the optimization of the tilmicosin dry suspension provided by the invention, each 100 g of the dry suspension comprises the following raw materials by weight: 18-20 parts of tilmicosin, 15-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 2-5 parts of carbomer, 3-5 parts of poloxamer, 8-10 parts of carboxymethyl starch sodium, 0.3-0.5 part of silicon dioxide, 0.15-0.2 part of a phagostimulant and 34.3-53.6 parts of glucose.
Further, as the optimization of the tilmicosin dry suspension provided by the invention, each 100 parts of the dry suspension comprise the following raw materials by weight: 20 parts of tilmicosin, 20 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 2 parts of carbomer, 1883 parts of poloxamer, 10 parts of carboxymethyl starch sodium, 0.5 part of silicon dioxide, 0.2 part of phagostimulant and 44.3 parts of glucose.
In another method, the invention also provides a preparation method of the tilmicosin dry suspension, and the dry suspension is prepared according to the following steps:
(1) every 100 parts of dry suspension comprises the following raw materials by weight: 10-20 parts of tilmicosin, 14-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 1-5 parts of carbomer, 1-5 parts of poloxamer, 5-10 parts of carboxymethyl starch sodium, 0.2-0.5 part of silicon dioxide, 0.1-0.2 part of a phagostimulant and 34.3-68.7 parts of glucose;
(2) adding the materials in the step (1) into a wet granulator, starting a stirring paddle, and mixing, wherein the stirring speed is set to be 200r/min, and the time is set to be 5 minutes;
(3) the rotating speed of the stirring paddle is kept unchanged, meanwhile, the cutter is started to carry out mixing cutting, and a proper amount of wetting agent is slowly added. As the amount of the wetting agent is increased, the viscosity of the material is correspondingly increased, so that the rotating speeds of the stirring paddle and the cutter are increased to carry out wet mixing and granulation. Sieving the prepared soft material with a third sieve to prepare particles;
(4) putting the prepared granules into an electric heating forced air drying oven, drying for 15 minutes at 50 ℃, and turning the granules once every 5 minutes;
(5) and after drying the particles, sieving the particles respectively through a first sieve and a fifth sieve to complete the particles, and finally obtaining the tilmicosin dry suspension.
(III) advantageous effects
The invention provides a tilmicosin dry suspension and a preparation method thereof, wherein the tilmicosin dry suspension is composed of tilmicosin and proper diluents, suspending agents, wetting agents, disintegrating agents, feeding promoting agents and other auxiliary materials. The tilmicosin dry suspension is added with the carboxymethyl starch sodium and the silicon dioxide as the disintegrating agents, so that the medicament can be uniformly dispersed without strong shaking or stirring in clinical application, and is convenient to use; through quality evaluation of the tilmicosin dry suspension, such as deposition volume ratio, dispersion speed, dissolution rate and the like, the tilmicosin dry suspension has good dispersibility in water, can act on livestock and poultry through drinking water administration, has wide action range, high stability and good taste masking effect, can avoid the damage of tilmicosin in gastric acid, and can be absorbed in the body best. The pharmacokinetic parameters prove that the medicament has good slow release effect in a body, and has the beneficial effects of high safety, good bioavailability, wide application range, convenience in administration and low production cost.
Drawings
FIG. 1 is a graph showing the dissolution rates of three different batches of samples prepared in example 2.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The formulation of this example (100 parts dry suspension) consisted of:
10 parts of tilmicosin, 14 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 1 part of carbomer, 1881 part of poloxamer, 5 parts of sodium carboxymethyl starch, 0.2 part of silicon dioxide, 0.1 part of phagostimulant and 68.7 parts of glucose;
the preparation process comprises the following steps:
(1) every 100 parts of dry suspension comprises the following raw materials by weight: 10 parts of tilmicosin, 14 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 1 part of carbomer, 1881 part of poloxamer, 5 parts of sodium carboxymethyl starch, 0.2 part of silicon dioxide, 0.1 part of phagostimulant and 68.7 parts of glucose;
(2) adding the materials in the step (1) into a wet granulator, starting a stirring paddle, and mixing, wherein the stirring speed is set to be 200r/min, and the time is set to be 5 minutes;
(3) the rotating speed of the stirring paddle is kept unchanged, meanwhile, the cutter is started to carry out mixing cutting, and a proper amount of wetting agent is slowly added. As the amount of the wetting agent is increased, the viscosity of the material is correspondingly increased, so that the rotating speeds of the stirring paddle and the cutter are increased to carry out wet mixing and granulation. And sieving the prepared soft material with a third sieve to prepare particles.
(4) And putting the prepared granules into an electric heating forced air drying oven, drying for 15 minutes at 50 ℃, and turning the granules once every 5 minutes.
(5) And after drying the particles, sieving the particles respectively through a first sieve and a fifth sieve to complete the particles, and finally obtaining the tilmicosin dry suspension.
Example 2
The formulation of this example (100 parts dry suspension) consisted of:
20 parts of tilmicosin, 20 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 2 parts of carbomer, 1883 parts of poloxamer, 10 parts of sodium carboxymethyl starch, 0.5 part of silicon dioxide, 0.2 part of a phagostimulant and 44.3 parts of glucose.
The preparation process is the same as in example 1.
Example 3
The formulation of this example (100 parts dry suspension) consisted of:
14 parts of tilmicosin, 14 parts of Arabic gum, 1.2 parts of carbomer, 1881.5 parts of poloxamer, 6 parts of carboxymethyl starch sodium, 0.3 part of silicon dioxide, 0.15 part of a phagostimulant and 62.85 parts of glucose.
The preparation process is the same as in example 1.
Example 4
The formulation of this example (100 parts dry suspension) consisted of:
18 parts of tilmicosin, 18 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 1.8 parts of carbomer, 1882.5 parts of poloxamer, 8 parts of sodium carboxymethyl starch, 0.4 part of silicon dioxide, 0.2 part of phagostimulant and 51.1 parts of glucose.
The preparation process is the same as in example 1.
Example 5
The formulation of this example (100 parts dry suspension) consisted of:
15 parts of tilmicosin, 15 parts of Arabic gum, 1.5 parts of carbomer, 1882 parts of poloxamer, 7.5 parts of carboxymethyl starch sodium, 0.3 part of silicon dioxide, 0.2 part of phagostimulant and 58.5 parts of glucose.
The preparation process is the same as in example 1.
Example 6
The formulation of this example (100 parts dry suspension) consisted of:
15 parts of tilmicosin, 14 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 1 part of carbomer, 0.5 part of carbomer, 1883.5 parts of poloxamer, 7.5 parts of carboxymethyl starch sodium, 0.3 part of silicon dioxide, 0.2 part of phagostimulant and 58 parts of glucose.
The preparation process is the same as in example 1.
Example 7
The formulation of this example (100 parts dry suspension) consisted of:
20 parts of tilmicosin, 15 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 5 parts of Arabic gum, 5 parts of carbomer, 1882 parts of poloxamer, 10 parts of carboxymethyl starch sodium, 0.5 part of silicon dioxide, 0.1 part of phagostimulant and 42.4 parts of glucose.
The preparation process is the same as in example 1.
Example 8
The formulation of this example (100 parts dry suspension) consisted of:
20 parts of tilmicosin, 25 parts of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL), 1.5 parts of carbomer, 5 parts of poloxamer, 7.5 parts of carboxymethyl starch sodium, 0.3 part of silicon dioxide, 0.2 part of phagostimulant and 40.5 parts of glucose.
The preparation process is the same as in example 1
Example 9
The formulation of this example (100 parts dry suspension) consisted of:
18 parts of tilmicosin, 20 parts of Arabic gum, 1.5 parts of carbomer, 1882 parts of poloxamer, 7.5 parts of carboxymethyl starch sodium, 0.3 part of silicon dioxide, 0.2 part of phagostimulant and 50.5 parts of glucose.
The preparation process is the same as in example 1.
The advantageous effects of the present invention are illustrated by the following test examples
Taking the formula and the process of the embodiment 2 to prepare the tilmicosin dry suspension as an example, the quality evaluation and the bioequivalence evaluation are carried out.
1. Quality research of tilmicosin dry suspension
(1) Volume reduction ratio
Taking 2 g of tilmicosin dry suspension, placing the tilmicosin dry suspension into a 50 ml measuring cylinder with a plug, adding ultrapure water to 50 ml, sealing, shaking forcefully for 1 minute, and recording the initial height H of the suspension0Standing for 3 hours, recording the final height H of the suspension, and using H/H0The sedimentation volume ratio was calculated. The results of the measurements (table 1) show that the sedimentation volume ratios of the three batches are all greater than 0.9, which is in accordance with the regulations.
TABLE 1 sedimentation volume ratio measurement results
(2) Dispersibility
The dispersibility test of tilmicosin dry suspension is carried out by 2 times of high dosage concentration in clinical use. Placing a certain amount of tilmicosin dry suspension in a measuring cylinder with a water stopper, turning the measuring cylinder up and down for 10 times, standing the measuring cylinder for 30 minutes, and marking the measuring cylinder as good dispersibility without generating precipitates; turning over the mixture up and down for 20 times, standing for 30 minutes, and marking the mixture as good dispersibility without generating precipitates; the non-uniform dispersion was recorded as "poor". The measurement results show that (table 1), the three samples have better dispersibility.
(3) Dynamic viscosity
According to the third method of 0633 viscosity measurement, which is page 100 of appendix of the first part of the 2015 edition of Chinese veterinary pharmacopoeia, the sedimentation suspension is taken, mixed uniformly, and the dynamic viscosity of the suspension is measured by a digital viscometer with a number 1 rotor at the rotating speed of 100 r/min. The measurement results show that the kinematic viscosity of the three samples at 25 ℃ does not exceed 150 mPas, and the kinematic viscosity meets the specification (Table 1). All three samples had better redispersibility.
(4) Dissolution rate
Taking the product, taking 900mL of pH6.8 phosphate solution as dissolution medium, rotating at 50r/min, taking 5mL of solution after 45 minutes, filtering, detecting by sample injection, and calculating dissolution rate. Taking tilmicosin dry suspension, taking 900ml of pH6.80 phosphate buffer solution as a dissolution medium according to a dissolution and release rate determination method (second method of appendix 0931), operating according to the method at a rotating speed of 50 revolutions per minute, taking a proper amount of solution after 45 minutes, filtering, taking subsequent filtrate, respectively determining according to chromatographic conditions under a content determination item, wherein the detection wavelength is 280nm, and calculating the dissolution rates of three batches of samples. The results show (table 2 and fig. 1) that the three batches of samples have good dissolution uniformity and meet the dissolution requirements.
TABLE 2 comparison of dissolution curves for three samples
2. Bioequivalence evaluation of tilmicosin dry suspension
This section is intended to further illustrate the bioequivalence evaluation of the tilmicosin dry suspension of the present invention, using the drug substance of tilmicosin dry suspension prepared in example 2.
(1) Laboratory animal
And (3) experimental animal selection: broiler chickens (Ross 317) are half of each male parent, the weight of the broiler chickens is 1.5-1.8 kg when the broiler chickens are selected, the broiler chickens are 240 randomly divided into two groups, each group comprises 120 experimental groups and a control group, all experimental chickens are placed into an isolator, each chicken is sequentially worn with a foot ring before the experimental chickens are placed into the isolator, and about 30 chickens are placed into each isolator.
Experimental animal feeding conditions: the experimental animal room is provided with a positive-negative pressure chicken isolator which is divided into an upper decomposable part, a middle decomposable part and a lower decomposable part, wherein the upper part is a living cabin, the middle part is a dung cabin, and the lower part is a movable support. The front end of the living cabin is provided with a transfer window and an exhaust system, and the rear end is provided with an air inlet system.
The animal room and the isolator are firstly fumigated by formaldehyde and potassium permanganate for three days and then put into the test chicken. During the study, the isolators used to feed test chickens were maintained at a temperature of 18 ℃ to 25 ℃, a relative humidity of 30% to 50%, time of day/time of night: 20h/4h.
Feeding of experimental animals: according to the conventional chicken feeding method, commercial feed is fed every day, and free feeding and free drinking are carried out. 8: 00. 17: 00 every water replenishing and material supplementing is carried out once. The drinking water meets the relevant regulations of urban drinking water, and the feed meets the requirements of feed sanitation standards. The feed consists of corn, bean pulp, peanut meal, corn protein powder, sodium chloride, methionine and the like.
(2) Test drug
Experimental groups: the tilmicosin dry suspension prepared in the example 2 meets the quality standard of the tilmicosin dry suspension through detection.
Control group: tilmicosin solution, specification: 25%, lot C79662, a product of an import company, which was tested to meet the Ministry of agriculture's No. 1269 bulletin quality standards.
Administration dose: the test is calculated by tilmicosin, and the experimental group and the control group are both administrated orally once according to the measurement of 30 mg/kgbw.
(3) Drug delivery and sample collection
The administration mode comprises the following steps: the oral administration is carried out;
the administration method comprises the following steps: when in administration, the liquid medicine in the syringe is completely filled into the chicken body, the stomach filling needle is flushed by 3-mL of normal saline and is taken (the administration process is controlled to be finished within 1 minute), and the timing is started.
Collection of test samples
And (3) fixing: the chicken is kept in a side lying mode, a remaining needle is arranged in the inferior pterygoid vein, and the chicken is detached after blood sampling for 2 hours.
Blood sampling time points: 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h and 24h after administration.
Collecting samples: approximately 1.5mL of subeteran venous blood was collected into a disposable negative pressure blood collection tube (heparin sodium). The recording personnel carefully checked and numbered each plasma sample collected.
(4) Determination of tilmicosin concentration in plasma samples
A detection instrument: waters e2695 liquid chromatograph equipped with ultraviolet detector. Liquid chromatography tandem mass spectrometer Thermo Fisher TSQ Quantiva, point-spray ion source.
Tilmicosin standard substance: 953% of the total amount, batch number K0311805, China institute for veterinary drugs.
(5) Data processing and analysis
Software: WinNonlin software (version 5.2.1), Pharsight, usa; SPSS software (version 20), IBM corporation, usa; graphad prism Software (version 6.0), Graphad Software, Inc. of USA.
Data input and analysis: the testers adopt Office Excel software to register and check the tilmicosin detection results, data statistics and analyst review are carried out, WinNonlin software is input, a non-compartmental analysis method is adopted to carry out mechanical acidification on the tilmicosin concentration result in each chicken plasma, and pharmacokinetic parameters including area under blood concentration-time curve (AUC)0→t、AUC0→∞) Peak concentration (C)max) Time to peak (T)max) And elimination half-life (t)1/2β) And the like. Then the AUC0→t、AUC0→∞After logarithmic conversion from Cmax, the input to WinNonlin software gave a 90% confidence interval for the tested formulation.
The judgment principle is as follows: evaluation according to the 90% confidence interval method, AUC0→t、AUC0→∞After logarithmic transformation with Cmax, the 90% confidence interval of AUC0 → t, AUC0 → ∞ is between 80% and 125%, and the 90% confidence interval with Cmax is between 70% and 143%, then the bioequivalence of the two preparations is judged.
(6) Test results
Table 3 pharmacokinetic parameters of tilmicosin in chicken plasma in experimental and control groups: (
n＝60)
| Pharmacokinetic parameters | Experimental group | Control group |
| Lambda_z(1/h) | 0.06±0.02 | 0.07±0.05 |
| t1/2β(h) | 12.37±3.51 | 12.87±4.59 |
| Tmax(h) | 3.26±2.09 | 3.34±2.22 |
| Cmax(ng/mL) | 1271.25±655.53 | 1234.26±933.82 |
| AUC0→t(h*ng/mL) | 7440.31±2256.82 | 6873.05±3108.60 |
| AUC0→∞(h*ng/mL) | 8710.66±2767.56 | 8211.11±3558.98 |
| MRT0→t(h) | 11.61±2.35 | 11.45±2.43 |
| MRT0→∞(h) | 17.48±3.79 | 18.50±4.41 |
And (4) conclusion: the relevant pharmacokinetic parameters are shown in table 3. Pharmacokinetic parameter AUC of control group preparation and experimental group preparation0→t、AUC0→∞And CmaxAfter natural logarithm conversion, the experimental preparation Ln (AUC) is analyzed by WinNonlin software0→t) And Ln (AUC)0→∞) The 90% confidence intervals of the compounds are respectively 99.37% -103.56% and 99.07% -103.04%, which are both between 80% -125% of the specification; ln (C)max) The 90% confidence interval of the two preparations is respectively 98.87% -105.28%, and the two preparations have bioequivalence between 70% -143% of the specified range.
The preparation used in the control group is oral liquid and liquid, the medicine is dispersed in a molecular form, the preparation used in the experimental group is dry suspension, and the medicine is dispersed in a particle form. Compared with a control group, the peak reaching time, the blood concentration and the peak reaching concentration of the experimental group are all higher than those of the control group, which shows that the tilmicosin dry suspension has better bioavailability and better clinical use effect.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (4)
1. The tilmicosin dry suspension is characterized by comprising the following raw materials in parts by weight per 100: 10-20 parts of tilmicosin, 14-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 1-5 parts of carbomer, 1-5 parts of poloxamer, 5-10 parts of carboxymethyl starch sodium, 0.2-0.5 part of silicon dioxide, 0.1-0.2 part of a phagostimulant and 34.3-68.7 parts of glucose.
2. The tilmicosin dry suspension according to claim 1, wherein the dry suspension comprises the following raw materials by weight per 100 parts: 18-20 parts of tilmicosin, 15-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 2-5 parts of carbomer, 3-5 parts of poloxamer, 8-10 parts of carboxymethyl starch sodium, 0.3-0.5 part of silicon dioxide, 0.15-0.2 part of a phagostimulant and 34.3-53.6 parts of glucose.
3. The tilmicosin dry suspension according to claim 2, wherein the dry suspension comprises the following raw materials by weight per 100 parts: 20 parts of tilmicosin, 20 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 2 parts of carbomer, 1883 parts of poloxamer, 10 parts of carboxymethyl starch sodium, 0.5 part of silicon dioxide, 0.2 part of phagostimulant and 44.3 parts of glucose.
4. The method of preparing a tilmicosin dry suspension of any one of claims 1 to 3, wherein the dry suspension is prepared by the steps of:
(1) every 100 parts of dry suspension comprises the following raw materials by weight: 10-20 parts of tilmicosin, 14-25 parts of one or two of microcrystalline cellulose-sodium carboxymethyl cellulose colloidal mixture (Avicel CL) and Arabic gum, 1-5 parts of carbomer, 1-5 parts of poloxamer, 5-10 parts of carboxymethyl starch sodium, 0.2-0.5 part of silicon dioxide, 0.1-0.2 part of a phagostimulant and 34.3-68.7 parts of glucose;
(2) and (3) adding the materials in the step (1) into a wet granulator, starting a stirring paddle, and mixing, wherein the stirring speed is set to be 200r/min, and the time is set to be 5 minutes.
(3) The rotating speed of the stirring paddle is kept unchanged, meanwhile, the cutter is started to carry out mixing cutting, and a proper amount of wetting agent is slowly added. As the amount of the wetting agent is increased, the viscosity of the material is correspondingly increased, so that the rotating speeds of the stirring paddle and the cutter are increased to carry out wet mixing and granulation. And sieving the prepared soft material with a third sieve to prepare particles.
(4) And putting the prepared granules into an electric heating forced air drying oven, drying for 15 minutes at 50 ℃, and turning the granules once every 5 minutes.
(5) And after drying the particles, sieving the particles by a first sieve and a fifth sieve respectively, and finishing the particles to obtain the tilmicosin dry suspension.
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| CN117398347A (en) * | 2023-12-15 | 2024-01-16 | 山东国邦药业有限公司 | Tilmicosin dry suspension and preparation method thereof |
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