CN111617032A - Ibuprofen medicinal fiber suspension and preparation method thereof - Google Patents
Ibuprofen medicinal fiber suspension and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an ibuprofen drug fiber suspension and a preparation method thereof, belonging to the technical field of sustained-release medicaments. The invention prepares an ibuprofen medicament fiber suspension which can prolong the half-life period of ibuprofen to 6.926h and the peak reaching time TmaxAs long as 2.5h, the peak concentration Cmax was reduced to 19.51. mu.g.mL‑1Has obvious in vivo slow release effect. The preparation method provided by the invention has high production efficiency, reduces the production cost, can be carried out in a glass reaction kettle in the whole process, is easy to control parameters, and is basically not influenced by external conditions.
Description
Technical Field
The invention relates to an ibuprofen drug fiber suspension and a preparation method thereof, belonging to the technical field of sustained-release medicaments.
Background
Ibuprofen having the molecular formula C13H18O2Molecular weight of 206.28, chemical name of (2S) -2- [4- (2-methylpropyl) phenyl]Propionic acid, CAS number 51146-56-6, is divided into the levorotatory and dextrorotatory forms. Ibuprofen is the only commonly recommended antipyretic for children by WHO and FDA in the United states, and is also a first choice antipyretic and anti-inflammatory for children.
Ibuprofen is rapidly absorbed by oral administration, has light adverse reaction, but can cause gastrointestinal irritation reaction such as abdominal distension, dyspepsia, nausea, emesis, diarrhea, digestive tract ulcer and the like after long-term large-scale administration. In addition, because ibuprofen has a short half-life, frequent administration is required to maintain therapeutic concentrations, which further increases the gastrointestinal response of the drug, even causes gastrointestinal bleeding, while also providing enhanced renal injury.
Therefore, there is a strong need for a sustained release formulation of ibuprofen with a long half-life, but no better product is available.
Disclosure of Invention
In order to solve the problems, the invention provides an ibuprofen medicinal fiber suspension and a preparation method thereof, wherein a coating technology is adopted to control the release of a medicament, so that the medicinal fiber suspension which is administrated once a day is prepared, and a patient only needs to take the medicinal fiber suspension once a day to achieve a treatment effect.
The technical scheme of the invention is as follows:
the invention provides an ibuprofen medicament fiber suspension, which comprises ibuprofen, ion exchange fibers, an impregnant, auxiliary materials, a plasticizer, a suspending agent, sucrose, liquid paraffin and span 80; the mass ratio of the ibuprofen, the ion exchange fibers, the auxiliary materials, the suspending agent and the sucrose is 10:10-20:1-2:10-20: 10-20; the volume ratio of the liquid paraffin to the span 80 is 20-30: 1.
Further, the impregnant is one or more of methyl cellulose, glycerol and PEG 4000.
Further, the auxiliary material is one or more of methacrylic acid copolymer, methacrylate copolymer, ethyl cellulose, methyl cellulose, cellulose nitrate, polyvinyl acetate polymer, acrylic resin, cellulose acetate or polyvinyl chloride.
Further, the plasticizer is one of PEG400, dibutyl phthalate, acetyl tributyl citrate, diethyl phthalate and triethyl citrate.
Further, the suspending agent is one or more of PVP, HPMC, tragacanth gum, xanthan gum, acacia, Carbopol and Avicel RC 591.
Further, a flavoring agent and a preservative are also included; the flavoring agent is one or more of aspartame, orange essence and strawberry essence; the preservative is one or more of ethyl p-hydroxybenzoate and propyl p-hydroxybenzoate.
The invention also provides a preparation method of the ibuprofen medicament fiber suspension, which comprises the following steps:
(1) preparing drug-loaded fibers: adding ibuprofen into deionized water for dissolving, stirring, adding ion exchange fiber, washing away unbound medicine on the fiber surface with deionized water when the medicine concentration in the solution is not reduced with time, and drying at 40-60 deg.C for 1-3h to obtain medicine-carrying fiber;
(2) impregnation of the drug-loaded fiber: adding the drug-loaded fibers obtained in the step (1) into an aqueous solution of an impregnant, uniformly stirring and drying, and sieving with a 80-100-mesh sieve to obtain impregnated drug-loaded fibers;
(3) the preparation of the drug fiber microcapsule comprises the following steps:
(a) preparation of dispersed phase: dissolving adjuvants and plasticizer with slow release effect in acetone, adding the impregnated drug-loaded fiber, stirring, and making into dispersed phase;
(b) preparation of continuous phase: adding liquid paraffin and span 80 into a glass reaction kettle, and uniformly stirring to obtain a continuous phase;
(c) circularly introducing heated water into the outer layer of the glass reaction kettle added with the continuous phase prepared in the step (b), adding the dispersed phase prepared in the step (a) when the temperature of the continuous phase in the glass reaction kettle rises to 50-60 ℃, adopting an ethanol solution as a condensed liquid, and vacuumizing at 0.08-0.12Mpa until acetone is not evaporated any more; taking out the liquid in the glass reaction kettle, carrying out suction filtration, washing with n-hexane, and drying to obtain the medicinal fiber microcapsule; the temperature of the heated water is 40-45 ℃;
(5) preparing ibuprofen medicament fiber suspension: adding deionized water into a glass reaction kettle, adjusting the rotating speed, adding the drug fiber microcapsule prepared in the step (3), adding a suspending agent and sucrose, and uniformly stirring to obtain an ibuprofen drug fiber suspension;
the mass ratio of the ibuprofen to the ion exchange fibers to the auxiliary materials to the suspending agent to the sucrose is 10:10-20:1-2:10-20: 10-20; the volume ratio of the liquid paraffin to the span 80 is 20-30: 1.
Further, the concentration of the aqueous solution of the impregnant in the step (2) is 10-30%; the stirring time is 0.5-1.5 h; the drying condition is drying at 40-60 ℃ for 0.5-1 h.
Further, in the step (b), the volume ratio of the liquid paraffin to the span 80 is 20-30: 1; the stirring condition is that the rotating speed is adjusted to 200-220rpm, and the stirring is continuously carried out for 0.5-1 h;
further, in step (c), the temperature of the ethanol is-10 ℃; the drying condition is drying in an oven at 40-60 ℃ for 1-2 h.
The invention has the beneficial effects that:
the invention prepares an ibuprofen medicament fiber suspension which can prolong the half-life period of ibuprofen to 6.926h, prolong the peak reaching time Tmax to 2.5h and reduce the peak concentration Cmax to 19.51 mu g/mL-1Has obvious in vivo slow release effect. The preparation method has high production efficiency, reduces the production cost, can be carried out in a glass reaction kettle in the whole process, is easy to control parameters,and is substantially unaffected by external conditions.
Drawings
Figure 1 is a graph of the in vitro release profile of ibuprofen drug fiber suspension (5mL) prepared in example 1.
Figure 2 is a graph of the in vivo release of ibuprofen pharmaceutical fiber suspension (5mL) prepared in example 1 versus a commercially available dexibuprofen oral suspension (5mL of 1mg/mL in water).
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings and examples.
The glass reaction kettle is purchased from Shanghai Prohua instruments and equipment Limited company.
EXAMPLE 1 preparation of ibuprofen pharmaceutical fiber suspension
(1) Preparing drug-loaded fibers:
dissolving 10g ibuprofen in 1L deionized water, stirring at 1000rpm on a magnetic stirrer, adding 20g ion exchange fiber, sampling at regular time, and measuring the concentration of the drug in the solution. When the concentration of the drug is not reduced with time any more, the balance is achieved, the deionized water is used for washing away the unbound drug on the surface of the fiber, and the ibuprofen drug-loaded fiber is obtained after drying for 2 hours at 60 ℃.
(2) Impregnation of the drug-loaded fiber:
30g of ibuprofen drug-loaded fiber is added into 1L of 10 percent PEG4000 aqueous solution, stirred for 1h, dried for 0.5h at 60 ℃, and sieved by a 100-mesh sieve to obtain the soaked ibuprofen drug-loaded fiber.
(3) Preparation of the drug fiber microcapsule:
preparation of dispersed phase: 2g of acrylic resin and 2mL of triethyl citrate
Dissolved in 960mL acetone, 30g of impregnated ibuprofen loaded fiber was added and stirred on a magnetic stirrer at 1000rpm for 0.5h to prepare a dispersed phase.
Preparing a continuous phase: adding 2900mL of liquid paraffin and 120mL of span 80 into a glass reaction kettle, starting a stirring paddle, adjusting the rotating speed to 200rpm, and continuously stirring for 0.5h to obtain a continuous phase.
Thirdly, water heated to 40 ℃ is circularly led into the outer layer of the glass reaction kettle, when the temperature of the continuous phase in the glass reaction kettle rises to the preset temperature, the dispersed phase is slowly added, ethanol at minus 10 ℃ is adopted as condensed liquid, and meanwhile, the vacuum pumping (0.1Mpa) is carried out until the acetone is not evaporated. And (3) after coating, taking out the liquid in the glass reaction kettle, performing suction filtration, washing for 3 times by using normal hexane, placing the sample in a 50 ℃ oven, and drying for 1h to obtain the drug resin microcapsule.
(4) Preparing ibuprofen medicament fiber suspension:
adding 2L of deionized water into a glass reaction kettle, adjusting the rotating speed to 200rpm, adding 30g of ibuprofen medicament fiber microcapsules, adding 20g of Avicel RC591 and 20g of cane sugar, and stirring for 1h to obtain the ibuprofen medicament fiber suspension. In addition, in order to improve the taste of the suspension, 20mg of strawberry flavor was added. In order to ensure the stability of the main drug, 20mg of ethyl p-hydroxybenzoate was added.
EXAMPLE 2 preparation of ibuprofen pharmaceutical fiber suspension
(1) Preparing drug-loaded fibers:
dissolving 10g ibuprofen in 1L deionized water, stirring at 1000rpm on a magnetic stirrer, adding 20g ion exchange fiber, sampling at regular time, and measuring the concentration of the drug in the solution. When the concentration of the drug is not reduced with time any more, the balance is achieved, the deionized water is used for washing away the unbound drug on the surface of the fiber, and the ibuprofen drug-loaded fiber is obtained after drying for 2 hours at the temperature of 40 ℃.
(2) Impregnation of drug-loaded fibers
Adding 30g ibuprofen drug-loaded fiber into 1L 30% glycerol water solution, stirring for 1h, drying at 60 deg.C for 0.5h, and sieving with 100 mesh sieve to obtain impregnated ibuprofen drug fiber.
(3) Preparation of drug fiber microcapsule
Preparation of dispersed phase: 5g of methacrylic acid copolymer and 2mL of PEG400 were dissolved in 960mL of ethyl acetate, 30g of impregnated ibuprofen loaded fibers were added and stirred on a magnetic stirrer at 1000rpm for 0.5h to prepare a dispersed phase.
Preparing a continuous phase: adding 2900mL of liquid paraffin and 120mL of span 80 into a glass reaction kettle, starting a stirring paddle, adjusting the rotating speed to 200rpm, and continuously stirring for 0.5h to obtain a continuous phase.
Thirdly, water heated to 40 ℃ is circularly led into the outer layer of the glass reaction kettle, when the temperature of the continuous phase in the glass reaction kettle rises to the preset temperature, the dispersed phase is slowly added, ethanol at minus 10 ℃ is adopted as condensed liquid, and meanwhile, the vacuum pumping (0.1Mpa) is carried out until the acetone is not evaporated. And (3) after coating, taking out the liquid in the glass reaction kettle, performing suction filtration, washing for 3 times by using normal hexane, placing the sample in a 50 ℃ oven, and drying for 1h to obtain the medicinal fiber microcapsule.
(4) Preparation of ibuprofen medicinal fiber suspension
Adding 2L of deionized water into a glass reaction kettle, adjusting the rotating speed to 200rpm, adding 30g of ibuprofen medicament fiber microcapsules, adding 20g of xanthan gum and 20g of sucrose, and stirring for 1h to obtain the ibuprofen medicament fiber suspension. In addition, 200mg of orange essence may also be added to improve the taste of the suspension. In order to ensure the stability of the main drug, 10mg of propyl p-hydroxybenzoate can be added.
Example 3: process for preparing ibuprofen pharmaceutical fiber suspension
(1) Preparation of drug-loaded fibers
Dissolving 10g ibuprofen in 1L deionized water, stirring at 1000rpm on a magnetic stirrer, adding 20g ion exchange fiber, sampling at regular time, and measuring the concentration of the drug in the solution. When the concentration of the drug is not reduced with time any more, the balance is achieved, the deionized water is used for washing away the unbound drug on the surface of the fiber, and the ibuprofen drug-loaded fiber is obtained after drying for 2 hours at 50 ℃.
(2) Impregnation of drug-loaded fibers
30g of ibuprofen drug-loaded fiber is added into 1L of 20 percent PEG4000 aqueous solution, stirred for 1h, dried for 0.5h at 60 ℃, and sieved by a 100-mesh sieve to obtain the soaked ibuprofen drug-loaded fiber.
(3) Preparation of drug fiber microcapsule
Preparation of dispersed phase: 3g of cellulose acetate and 2mL of diethyl phthalate were dissolved in 960mL of ethanol, 30g of impregnated ibuprofen drug loaded fiber was added, and the mixture was stirred on a magnetic stirrer at 1000rpm for 0.5h to prepare a dispersed phase.
Preparing a continuous phase: adding 2900mL of liquid paraffin and 120mL of span 80 into a glass reaction kettle, starting a stirring paddle, adjusting the rotating speed to 200rpm, and continuously stirring for 0.5h to obtain a continuous phase.
Thirdly, water heated to 40 ℃ is circularly led into the outer layer of the glass reaction kettle, when the temperature of the continuous phase in the glass reaction kettle rises to the preset temperature, the dispersed phase is slowly added, ethanol at minus 10 ℃ is adopted as condensed liquid, and meanwhile, the vacuum pumping (0.1Mpa) is carried out until the acetone is not evaporated. And (3) after coating, taking out the liquid in the glass reaction kettle, performing suction filtration, washing for 3 times by using normal hexane, placing the sample in a 50 ℃ oven, and drying for 1h to obtain the medicinal fiber microcapsule.
(4) Preparation of ibuprofen medicinal fiber suspension
Adding 2L of deionized water into a glass reaction kettle, adjusting the rotating speed to 200rpm, adding 30g of ibuprofen medicament fiber microcapsules, adding 20g of Carbopol and 20g of sucrose, and stirring for 1h to obtain the ibuprofen medicament fiber suspension. In addition, 30mg of aspartame may be added to improve the taste of the suspension. In order to ensure the stability of the main drug, 20mg of propyl p-hydroxybenzoate was added.
Example 4: process for preparing ibuprofen pharmaceutical fiber suspension
(1) Preparation of drug-loaded fibers
Dissolving 10g ibuprofen in 1L deionized water, stirring at 1000rpm on a magnetic stirrer, adding 20g ion exchange fiber, sampling at regular time, and measuring the concentration of the drug in the solution. When the concentration of the drug is not reduced along with the time, the balance is achieved, the deionized water is used for washing away the unbound drug on the surface of the fiber, and the ibuprofen drug-loaded fiber is obtained after drying for 2 hours at the temperature of 40-60 ℃.
(2) Impregnation of drug-loaded fibers
30g of ibuprofen drug-loaded fiber is added into 1L of aqueous solution of 15 percent PEG4000, stirred for 1 hour, dried for 0.5 hour at the temperature of 60 ℃, and sieved by a 100-mesh sieve to obtain the soaked ibuprofen drug-loaded fiber.
(3) Preparation of drug fiber microcapsule
Preparation of dispersed phase: dissolving 3.5g of ethyl cellulose and 2mL of dibutyl phthalate in ethanol, adding 30g of impregnated ibuprofen drug-loaded fiber, and stirring for 0.5h on a magnetic stirrer at 1000rpm to prepare a dispersed phase.
Preparing a continuous phase: adding 2900mL of liquid paraffin and 120mL of span 80 into a glass reaction kettle, starting a stirring paddle, adjusting the rotating speed to 200rpm, and continuously stirring for 0.5h to obtain a continuous phase.
Thirdly, water heated to 40 ℃ is circularly led into the outer layer of the glass reaction kettle, when the temperature of the continuous phase in the glass reaction kettle rises to the preset temperature, the dispersed phase is slowly added, ethanol at minus 10 ℃ is adopted as condensed liquid, and meanwhile, the vacuum pumping (0.1Mpa) is carried out until the acetone is not evaporated. And (3) after coating, taking out the liquid in the glass reaction kettle, performing suction filtration, washing for 3 times by using normal hexane, placing the sample in a 50 ℃ oven, and drying for 1h to obtain the medicinal fiber microcapsule.
(4) Preparation of ibuprofen medicinal fiber suspension
Adding 2L of deionized water into a glass reaction kettle, adjusting the rotating speed to 200rpm, adding 30g of ibuprofen medicament fiber microcapsules, adding 20g of Arabic gum and 20g of cane sugar, and stirring for 1 hour to obtain the ibuprofen medicament fiber suspension. In addition, 60mg of orange essence may also be added to improve the taste of the suspension. In order to ensure the stability of the main drug, 25mg of ethyl p-hydroxybenzoate was added.
Test example 1: in vitro release test
In vitro tests are important means for screening prescription determination processes, play an important role in quality control of preparations and are mainly investigated through dissolution rates. With 900mL of 0.4mol/L KH subjected to degassing treatment2PO4For releasing the medium, the speed is 50r/min and the temperature is 37 ℃. According to the operation of an addendum paddle method in Chinese pharmacopoeia 2015 edition, 5mL of ibuprofen pharmaceutical fiber suspension prepared in example 1 is taken from 0.5, 1, 2, 4, 6, 8, 10 and 12h respectively, is filtered through a 0.45-micrometer microporous membrane, an initial filtrate is discarded, a subsequent filtrate is taken for standby, corresponding media with the same temperature and the same volume are added in time, the absorbance of the subsequent filtrate is measured at 260nm, the concentration of sample liquid at different times is calculated according to a standard curve, and the relationship between the cumulative release amount of 12h and time is inspected.
Results are shown in FIG. 1, with three parallel runs, indicated as 1, 2, 3 in the figure; the results show that the ibuprofen drug fiber suspension prepared in example 1 has an in vitro release degree of 12h of 75-85%, so that the drug can be slowly released into the body.
Test example 2: stability test
The ibuprofen medicament fiber suspension prepared in the example 1 is subjected to high temperature, high humidity, illumination and air exposure experiments, and the result shows that the content, the dissolution rate of related substances and medicaments are not obviously changed and the stability is better under the conditions of high temperature (60 ℃), high humidity (75%), illumination (the illumination intensity is 4500Lx +/-500 Lx) and air exposure for 3 months.
Test example 3: in vivo pharmacokinetic Studies
Pharmacokinetics (pharmacokinetics) is a science that applies the principle of kinetics and mathematical processing methods to quantitatively describe the dynamic change law of processes such as absorption, distribution, metabolism and excretion of drugs entering the body through various routes, i.e., to study the relationship between the existing site, concentration and time of drugs in the body and to propose mathematical relations required for explaining these data.
SD rat pharmacokinetics studies of the ibuprofen pharmaceutical fiber suspension prepared in example 1 were performed using high performance liquid chromatography as the detection method.
12 SD rats were divided into A, B groups in a random distribution, fasting was initiated at 9 PM, and the next day was administered at 9 AM at a dose of 6mg/kg, during which time water was not deprived. A. B, two groups of SD rats respectively take in a commercially available dexibuprofen oral suspension and the ibuprofen medicament fiber suspension prepared in example 1 in a gastric lavage mode, blood sampling time points are set to be 0.5h, L h h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration, 0.5mL of eyeball blood of the rat is taken each time, 20 mu L of sample injection is accurately measured, the peak area is recorded, and the blood concentration of the ibuprofen medicament fiber suspension at each sampling point is calculated.
As shown in figure 2, compared with the commercial dexibuprofen oral suspension, the half-life t1/2 of the ibuprofen drug fiber suspension prepared in example 1 is prolonged from 2.356h to 6.926h, the peak reaching time Tmax is prolonged from 1h to 2.5h, and the peak concentration Cmax is increased from 26.69 mug. mL-1Reduced to 19.51 mug·mL-1(ii) a The blood concentration of rats taking the ibuprofen medicament fiber suspension prepared in the example 1 fluctuates in a small range, and the sustained-release effect in vivo is obvious.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. An ibuprofen medicament fiber suspension is characterized by comprising ibuprofen, ion exchange fibers, an impregnating agent, auxiliary materials, a plasticizer, a suspending agent, sucrose, liquid paraffin and span 80; the mass ratio of the ibuprofen, the ion exchange fibers, the auxiliary materials, the suspending agent and the sucrose is 10:10-20:1-2:10-20: 10-20; the volume ratio of the liquid paraffin to the span 80 is 20-30: 1.
2. The ibuprofen pharmaceutical fiber suspension according to claim 1, wherein the impregnant is one or more of methylcellulose, glycerol and PEG 4000.
3. The ibuprofen pharmaceutical fiber suspension according to claim 1, wherein the adjuvant is one or more of methacrylic acid copolymer, methacrylate ester copolymer, ethyl cellulose, methyl cellulose, cellulose nitrate, polyvinyl acetate polymer, acrylic resin, cellulose acetate or polyvinyl chloride.
4. The ibuprofen pharmaceutical fiber suspension according to claim 1, wherein said plasticizer is one of PEG400, dibutyl phthalate, acetyl tributyl citrate, diethyl phthalate, triethyl citrate.
5. The ibuprofen pharmaceutical fiber suspension according to claim 1, wherein the suspending agent is one or more of PVP, HPMC, tragacanth, xanthan gum, acacia, Carbopol, Avicel RC 591.
6. The ibuprofen pharmaceutical fiber suspension of claim 1, further comprising a flavoring agent and a preservative; the flavoring agent is one or more of aspartame, orange essence and strawberry essence; the preservative is one or more of ethyl p-hydroxybenzoate and propyl p-hydroxybenzoate.
7. A process for the preparation of the ibuprofen pharmaceutical fibre suspension according to any of claims 1 to 6, comprising the steps of:
(1) preparing drug-loaded fibers: adding ibuprofen into deionized water for dissolving, stirring, adding ion exchange fiber, washing away unbound medicine on the fiber surface with deionized water when the medicine concentration in the solution is not reduced with time, and drying at 40-60 deg.C for 1-3h to obtain medicine-carrying fiber;
(2) impregnation of the drug-loaded fiber: adding the drug-loaded fibers obtained in the step (1) into an aqueous solution of an impregnant, uniformly stirring and drying, and sieving with a 80-100-mesh sieve to obtain impregnated drug-loaded fibers;
(3) the preparation of the drug fiber microcapsule comprises the following steps:
(a) preparation of dispersed phase: dissolving adjuvants and plasticizer with slow release effect in acetone, adding the impregnated drug-loaded fiber, stirring, and making into dispersed phase;
(b) preparation of continuous phase: adding liquid paraffin and span 80 into a glass reaction kettle, and uniformly stirring to obtain a continuous phase;
(c) circularly introducing heated water into the outer layer of the glass reaction kettle added with the continuous phase prepared in the step (b), adding the dispersed phase prepared in the step (a) when the temperature of the continuous phase in the glass reaction kettle rises to 50-60 ℃, adopting an ethanol solution as a condensed liquid, and vacuumizing at 0.08-0.12Mpa until acetone is not evaporated any more; taking out the liquid in the glass reaction kettle, carrying out suction filtration, washing with n-hexane, and drying to obtain the medicinal fiber microcapsule; the temperature of the heated water is 40-45 ℃;
(4) preparing ibuprofen medicament fiber suspension: adding deionized water into a glass reaction kettle, adjusting the rotating speed, adding the drug fiber microcapsule prepared in the step (3), adding a suspending agent and sucrose, and uniformly stirring to obtain an ibuprofen drug fiber suspension;
the mass ratio of the ibuprofen to the ion exchange fibers to the auxiliary materials to the suspending agent to the sucrose is 10:10-20:1-2:10-20: 10-20; the volume ratio of the liquid paraffin to the span 80 is 20-30: 1.
8. The preparation method according to claim 7, wherein the concentration of the aqueous solution of the impregnant in the step (2) is 10-30%; the stirring time is 0.5-1.5 h; the drying condition is drying at 40-60 ℃ for 0.5-1 h.
9. The method according to claim 7, wherein in the step (b), the volume ratio of the liquid paraffin to span 80 is 20-30: 1; the stirring condition is that the rotation speed is adjusted to 200-220rpm, and the stirring is continued for 0.5-1 h.
10. The method according to claim 7, wherein in the step (c), the temperature of the ethanol is-10 ℃; the drying condition is drying in an oven at 40-60 ℃ for 1-2 h.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010651960.XA CN111617032A (en) | 2020-07-08 | 2020-07-08 | Ibuprofen medicinal fiber suspension and preparation method thereof |
| PCT/CN2020/102252 WO2022006946A1 (en) | 2020-07-08 | 2020-07-16 | Ibuprofen iatric fiber suspension and preparation method therefor |
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| CN202010651960.XA CN111617032A (en) | 2020-07-08 | 2020-07-08 | Ibuprofen medicinal fiber suspension and preparation method thereof |
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| CN114159391A (en) * | 2021-12-10 | 2022-03-11 | 卓和药业集团股份有限公司 | Rivastigmine bitartrate dry suspension and preparation method thereof |
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| AU2022201576A1 (en) * | 2022-03-08 | 2023-09-28 | Aft Pharmaceuticals Limited | Medication |
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| CN111297800B (en) * | 2020-04-10 | 2021-08-20 | 广州康健医学科技有限公司 | Ion exchange fiber chloroquine suspension and preparation method thereof |
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2020
- 2020-07-08 CN CN202010651960.XA patent/CN111617032A/en active Pending
- 2020-07-16 WO PCT/CN2020/102252 patent/WO2022006946A1/en active Application Filing
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