CN111544384A - Technology and preparation method of children ibuprofen over-the-counter drug - Google Patents
Technology and preparation method of children ibuprofen over-the-counter drug Download PDFInfo
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- CN111544384A CN111544384A CN202010488238.9A CN202010488238A CN111544384A CN 111544384 A CN111544384 A CN 111544384A CN 202010488238 A CN202010488238 A CN 202010488238A CN 111544384 A CN111544384 A CN 111544384A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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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
- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The invention belongs to the technical field of medicines, and discloses a drop for children, which is prepared from ibuprofen as a raw material, and a preparation method thereof. The drop is characterized in that every 1000ml drop contains the following components by mass: 20-600 g of ibuprofen, 15-500 g of L-arginine, 10-300 ml of glycerol, 0.3-20 g of steviosin, 0.03-2 g of essence and the balance of purified water. The invention adopts the capacity increasing technology to improve the solubility of the ibuprofen, solves the problem of improving the drug-loading rate due to the difficult dissolution of the ibuprofen in water, and simultaneously adopts the taste correcting technology, so that compared with other preparations, the dosage is reduced, the taste is good, the drug cost is reduced, the drug is convenient for children patients to use, and the compliance of the children drug is improved.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a drop taking ibuprofen as a raw material and a preparation method thereof.
Background
In the modern society, antipyretic analgesics become important medicines indispensable in human daily life, and are one of the most widely and extensively used medical varieties worldwide. In recent years, the market of antipyretic analgesics at home and abroad is on a steady growth trend, and the market is expected to be expanded continuously in future. Among a plurality of non-steroidal anti-inflammatory drugs, ibuprofen is widely applied with the advantages of definite anti-inflammatory, antipyretic and analgesic effects, small adverse reaction and the like, and becomes one of the best-selling over-the-counter drugs in the world. Ibuprofen, however, has been used clinically for nearly 40 years as an anti-inflammatory and analgesic agent, is considered the safest non-steroidal anti-inflammatory drug (NSAID), and is an over-the-counter drug. However, the current market probably has the following dosage forms for treating fever in children: oral liquid, tablet, suppository and injection have poor compliance for children.
However, because ibuprofen has extremely poor water solubility and meets clinical requirements of children for medication, the development of a dosage form suitable for the characteristics of children medication is expected by many doctors and parents to improve the compliance of children medication.
Disclosure of Invention
Based on the reasons, researchers in the laboratory make ibuprofen, cosolvent and flavoring agent into drops through experimental research, and then determine the preparation process of 'mixing ibuprofen and cosolvent with a proper proportion uniformly, adjusting the taste by using a proper amount of flavoring agent, preparing drops suitable for children to take medicine, filtering and sterilizing' through an optimization experiment of the preparation process.
The invention is realized by the following technical scheme.
Ibuprofen drops, characterized in that per 1000ml of drops they contain:
the preparation method comprises the following steps:
(1) mixing ibuprofen with cosolvent in proper proportion;
(2) weighing a proper amount of flavoring agent, completely dissolving the flavoring agent in water, and uniformly stirring for later use;
(3) adding the (1) into the (2), stirring and adding until the solution is completely dissolved for later use;
(4) adding the rest flavoring agent into the step (3), and dissolving with purified water to dilute to constant volume;
(5) filtering, encapsulating and sterilizing the prepared liquid to obtain the ibuprofen drop.
First, research of process experiment
1. Selection of Co-solvent
Ibuprofen is a weakly acidic drug, the solubility of ibuprofen in water and a weakly acidic solution is low, and the solubility of ibuprofen can be improved in an alkaline environment.
The main screening auxiliary materials take L-arginine and lysine as examples. The results are shown in Table 1.
TABLE 1 results of cosolvent selection study
And (3) knotting: the experiment result shows that the ibuprofen and the L-arginine can be dissolved when the molar ratio is 1: 0.8. The dosage is not obviously changed when being increased. Ibuprofen and lysine can be dissolved when the molar ratio is 1: 0.95. The dosage is not obviously changed when being increased. Therefore, arginine salt is formed by L-arginine and ibuprofen, and the problem of solubility is solved.
2. Selection of flavouring Agents
TABLE 2 examination of the amount of glycerol used
Glycerol is commonly used as a solvent and sweetener, an antibacterial agent, in oral solutions. Can be widely used in preparation and food.
The results and summary are: the glycerol with the dosage of 20% can relieve tongue sensation and pungent taste during administration, and is obvious 5-6 minutes after administration, wherein the 5-6 minutes can provide children with water or food, cover the taste of medicine, and improve compliance of administration.
TABLE 3 investigation of stevia Rebaudiana amounts
Since the medicine is for children, excessive additives should not be added, and stevioside is added at a concentration of 1.0g/100 ml.
TABLE 4 essence investigation
The essence is mainly used in a conventional amount, and the amount is determined by the taste and evaluation of testers.
The results and summary are: experimental results show that when the dosage of the glycerol is 20%, the numb tongue feeling and the spicy taste during administration can be relieved, and the feeling is obvious 5-6 minutes after administration, wherein the children can drink or eat water or food in 5-6 minutes, the taste of the medicine is covered, and the administration compliance is improved. Since the medicine is for children, excessive additives should not be added, and stevioside is added at a concentration of 1.0g/100 ml. The essence is mainly used in a conventional amount, and the amount is determined by the taste and evaluation of the testee.
3. Preparation of ibuprofen and cosolvent mixture
And (4) screening the dosage of the prescription. The results of the experiments are shown in Table 5 below.
TABLE 5 study results of prescription dose screening
And (4) conclusion: experimental results show that the dissolution effect is best when the molar ratio of ibuprofen to arginine is 1: 0.8. The L-arginine serving as the cosolvent meets the oral medicinal standard, has stable physicochemical property, better or ideal cosolvent effect, does not interfere the effect and toxicity of the main medicament, does not influence the content determination of the main medicament, and has the use basis of related documents.
4. Investigation of flavor addition sequence
The flavor prescription results are shown in Table 6 below.
The order of flavor addition was adjusted according to the prescription experiment and the results are shown in table 7.
And (3) knotting: the solution obtained by sequentially adding the flavoring agent in the formula 1 has stable physicochemical properties, does not influence the stability and content measurement of the main drug, has easily accepted taste and color, solves the problems of taste and tolerance, and improves the taste acceptability and the medication compliance of the drop.
Description of the drawings: the experimental result is a conclusive experimental result obtained on the basis of multiple experiments.
And (4) conclusion: through the experimental research, the preparation process of the ibuprofen drop for children is determined as follows: firstly, weighing ibuprofen, L-arginine and glycerol in a formula amount, and mixing the ibuprofen, the L-arginine and the glycerol in a certain ratio for later use; then, a proper amount (about 90-100ml) of purified water is weighed and added, the stevioside with the prescription amount is added and stirred until the mixture is completely dissolved, the mixture of the ibuprofen and the L-arginine glycerol is added while stirring, after the mixture is completely dissolved, the essence is added, the water is supplemented to 1000ml, the mixture is stirred uniformly, sand-type filtration is carried out, and the ibuprofen children oral drop is obtained after the mixture is subjected to selective sterilization by circulating steam at 121 ℃ for 15 min. "
Second, test of influence factors
The investigation items comprise properties, high temperature tests, high light tests, related substances and contents, and all the examinations are carried out according to the method in the quality standard research.
1. High temperature test
Ibuprofen drop (batch No. 20200106, specification 15 m: 6.0g) of the ibuprofen drop of the invention example 1 was sampled and placed in a thermostat at 40 ℃. + -. 2 ℃ for 10 days, and the samples were taken at 0 day, 5 days and 10 days for measurement, and the results are shown in Table 8 below.
2. Hard light test
The ibuprofen oral drop of the invention example 1 is taken for children. (batch No. 20200106, 15 ml: 6.0g) was placed in an illumination box at an illumination of 4500 lx. + -. 500lx for 10 days, and samples were taken at 0 days, 5 days, and 10 days for measurement, and the results are shown in Table 8 below.
TABLE 8 influence factor test results
And (4) test conclusion: the influence factor tests show that the ibuprofen children oral drop prepared by the process method has good stability and mouthfeel.
Preparation examples
Example 1
An ibuprofen drop for children is characterized by 400g of ibuprofen, 270g of L-arginine, 200ml of glycerol, 10g of steviosin and 1.0g of essence.
The preparation method comprises the following steps:
(1) weighing 400g of ibuprofen with the prescription amount and 270g (0.8mol) of L-arginine with the prescription amount of glycerol 200ml, and mixing for later use;
(2) weighing a proper amount (about 90-100ml) of purified water, adding 10g of stevioside according to the prescription amount, and stirring until the stevioside is completely dissolved;
(3) adding a mixture of ibuprofen and L-arginine while stirring;
(4) after all the components are dissolved, adding 1.0g of essence with the conventional amount, replenishing water to 1000ml, and uniformly stirring;
(5) the prepared liquid is filtered, filled, sealed and sterilized to obtain 66 ibuprofen drops of 15ml to 6.0 g.
Example 2
An ibuprofen drop for children is characterized by comprising 20g of ibuprofen, 20g of L-arginine, 90ml of glycerol, 5g of steviosin and 0.5g of essence.
The preparation method comprises the following steps:
(1) weighing 20g of ibuprofen and 20g of L-arginine according to the prescription amount, and mixing for later use;
(2) weighing appropriate amount (about 90-100ml) of purified water, adding 5g of steviosin, and stirring until the steviosin is completely dissolved;
(3) adding a mixture of ibuprofen and L-arginine while stirring;
(4) after the components are completely dissolved, 90ml of glycerol with the amount of the prescription and 0.5g of essence with the conventional amount are added, water is supplemented to 1000ml, and the mixture is stirred uniformly;
(5) and filtering, filling and sealing the prepared liquid, and sterilizing to obtain 66 ibuprofen drops with 1000 ml.
Example 3
An ibuprofen drop for children is characterized by comprising 200g of ibuprofen, 140g of L-arginine, 150ml of glycerol, 8g of steviosin and 0.8g of essence.
The preparation method comprises the following steps:
(1) weighing 200g of ibuprofen and 140g of L-arginine according to the prescription amount, and mixing for later use;
(2) weighing a proper amount (about 90-100ml) of purified water, adding 8g of stevioside according to the prescription amount, and stirring until the stevioside is completely dissolved;
(3) adding a mixture of ibuprofen and L-arginine while stirring;
(4) after the materials are completely dissolved, adding 150ml of glycerol and 0.8g of conventional essence, replenishing water to 1000ml, and stirring uniformly;
(5) and filtering, filling and sealing the prepared liquid, and sterilizing to obtain 66 ibuprofen drops with 1000 ml.
Example 4
An ibuprofen drop for children is characterized by 600g of ibuprofen, 500g of L-arginine, 350ml of glycerol, 15g of steviosin and 1.5g of essence.
The preparation method comprises the following steps:
(1) weighing 600g of ibuprofen and 500g of L-arginine according to the prescription amount, and mixing for later use;
(2) weighing a proper amount (about 90-100ml) of purified water, adding 15g of stevioside according to the prescription amount, and stirring until the stevioside is completely dissolved;
(3) adding a mixture of ibuprofen and L-arginine while stirring;
(4) after the components are completely dissolved, adding 350ml of glycerol and 1.5g of essence according to the prescription amount, supplementing water to 1000ml, and stirring uniformly;
(5) and filtering, filling and sealing the prepared liquid, and sterilizing to obtain 66 ibuprofen drops with 1000 ml.
Example 5
An ibuprofen drop for children is characterized by comprising 500g of ibuprofen, 450g of L-arginine, 250ml of glycerol, 12g of steviosin and 1.2g of essence.
The preparation method comprises the following steps:
(1) weighing 500g of ibuprofen and 450g of L-arginine according to the prescription amount, and mixing for later use;
(2) weighing a proper amount (about 90-100ml) of purified water, adding 12g of stevioside according to the prescription amount, and stirring until the stevioside is completely dissolved;
(3) adding a mixture of ibuprofen and L-arginine while stirring;
(4) after the components are completely dissolved, adding 250ml of glycerol and 1.2g of essence according to the prescription amount, replenishing water to 1000ml, and uniformly stirring;
(5) and filtering, filling and sealing the prepared liquid, and sterilizing to obtain 66 ibuprofen drops with 1000 ml.
Claims (3)
1. Ibuprofen drops, which take ibuprofen as an effective medicinal component, are characterized in that each 1000ml drop contains:
2. ibuprofen drops according to claim 1, characterized in that: the cosolvent is L-arginine; the flavoring agent is selected from two or three of steviosin, essence, and glycerol.
3. A method of preparing ibuprofen drops according to claim 1, characterized in that: firstly, ibuprofen and a cosolvent are uniformly mixed to be used as A for standby; secondly, adding part of flavoring agents into a proper amount of water to be completely dissolved, and using the mixture as B for standby; thirdly, adding the A while stirring the B, adding the rest flavoring agent after the A is completely dissolved, and dissolving and diluting the rest flavoring agent by using purified water to a constant volume; and fourthly, filtering, filling, sealing and sterilizing the prepared solution to obtain a finished product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010488238.9A CN111544384A (en) | 2020-05-29 | 2020-05-29 | Technology and preparation method of children ibuprofen over-the-counter drug |
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| CN202010488238.9A CN111544384A (en) | 2020-05-29 | 2020-05-29 | Technology and preparation method of children ibuprofen over-the-counter drug |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112156068A (en) * | 2020-11-05 | 2021-01-01 | 广州汇元医药科技有限公司 | Ibuprofen oral solution and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101564387A (en) * | 2008-04-25 | 2009-10-28 | 天津医科大学 | Oral arginine ibuprofen liquid preparation |
| CN106606476A (en) * | 2015-10-27 | 2017-05-03 | 康芝药业股份有限公司 | Ibuprofen suspension drops and preparation method thereof |
| CN109381426A (en) * | 2017-08-11 | 2019-02-26 | 北京人福军威医药技术开发有限公司 | A kind of ibuprofen oral spray and preparation method thereof |
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2020
- 2020-05-29 CN CN202010488238.9A patent/CN111544384A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101564387A (en) * | 2008-04-25 | 2009-10-28 | 天津医科大学 | Oral arginine ibuprofen liquid preparation |
| CN106606476A (en) * | 2015-10-27 | 2017-05-03 | 康芝药业股份有限公司 | Ibuprofen suspension drops and preparation method thereof |
| CN109381426A (en) * | 2017-08-11 | 2019-02-26 | 北京人福军威医药技术开发有限公司 | A kind of ibuprofen oral spray and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112156068A (en) * | 2020-11-05 | 2021-01-01 | 广州汇元医药科技有限公司 | Ibuprofen oral solution and preparation method thereof |
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