CN102068405A - Ketoprofen gel and preparation method thereof - Google Patents

Abstract

The invention discloses ketoprofen gel and a preparation method thereof, and the ketoprofen gel can be obtained by adding ketoprofen ethanol solution prepared by ketoprofen and anhydrous ethyl alcohol into a gel matrix prepared by polyethylene glycol PEG400, propylene glycol and carbopol 940NF and uniformly stirring, wherein the ketoprofen gel comprises the following raw materials by weight percent: 0.02-0.08% of ketoprofen, 15-40% of anhydrous ethyl alcohol, 40-80% of polyethylene glycol PEG400, 10-30% of propylene glycol and 0.5-2% of carbopol 940NF. The ketoprofen gel has the advantages that the stability is much better than ingredients, the storage is easy, and the ketoprofen gel is less prone to volatilization. Experimental results about the stability prove that the quality of the ketoprofen gel is more stable, and various indicators have no significant changes.

Description

A kind of ketoprofen gel and preparation method thereof

field of invention

The invention relates to a ketoprofen gel preparation and a preparation method thereof, belonging to the technical field of medicines. the

Background technique

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAI) with anti-inflammatory, antipyretic, and analgesic properties. Topical pharmaceutical formulations of ketoprofen and dexketoprofen are described in most scientific literature as irritants, Allergens, phototoxins and photoallergens. Ketoprofen is similar to other non-steroidal anti-inflammatory drugs, and has serious adverse reactions during clinical application, such as: ①digestive system symptoms such as stomach discomfort, stomach pain, heating, and diarrhea; ②allergic symptoms such as eruption and rash, ③ Major adverse reactions such as acute renal insufficiency, liver dysfunction, and peptic ulcer may occur. According to the characteristics that ketoprofen is mainly used to treat chronic rheumatoid arthritis, osteoarthritis, low back pain, periarthritis of shoulder, neck, shoulder and wrist syndrome, as well as anti-inflammatory and analgesic for trauma, in order to avoid the above adverse reactions, This study intends to use carbomer as a water-soluble material as a matrix, and make ketoprofen into a gel for external use. The purpose is to increase the local drug concentration, avoid side effects such as the gastrointestinal tract, and release the drug under control. The drug can be interrupted at any time, which is convenient. Medication, patient compliance is good. Because the oral dose of ketoprofen is relatively large, and the transdermal absorption is limited by the skin, the amount of drug penetration is usually very small. It is impossible for ketoprofen to achieve systemic administration through transdermal absorption, so it is considered to be made into topical application preparation. Formulations for topical application include powder formulations, semisolid formulations and liquid formulations. the

Gel is a new dosage form produced with the development of modern industry. It refers to the latex thick liquid or semi-solid preparation made of medicine and gel-forming excipients in uniform, suspension or emulsion form. Gels for external use refer to uniform or dizzy semi-solid preparations made of drugs and suitable excipients, which belong to a single-phase dispersion system, have swelling properties, syneresis, permeability and adhesion, and have cross-linked structures It also has a part of solid properties, which can closely adhere to the medication site for a long time, and can keep the semi-solid preparation in a certain shape when it is still, and can flow and deform under the action of external force. In topical formulations, these properties are often exploited to control the release of the drug or its adhesion to the skin. Because the hydrophilic gel feels good, is easy to wash off, and does not pollute clothes, there are many researches at present. The polymer materials constituting the aqueous gel matrix can be divided into natural polymers, semi-synthetic polymers, and synthetic polymer materials. Wherein the carbomer (Carbomer) in the synthetic macromolecular material is the most commonly used matrix, can obtain the uniform and stable system with it as matrix, is a kind of ideal gel matrix material, in recent years to its transdermal absorption preparation aspect The applied research is more extensive and the research is more extensive. the

Carbomer is a high-molecular polymer cross-linked with acrylic acid and propylene-based sucrose. It is a white, loose, acidic, hygroscopic powder with a slight special odor. Because the molecule contains a large number of shuttle groups, it is hydrophilic and can be dissolved in water. Swells rapidly, but does not dissolve, and has a low viscosity. When neutralized with alkali, it gradually dissolves in water, alcohol and glycerin, and its viscosity increases rapidly. It forms a clear solution at low concentration, and forms a translucent gel at high concentration. If ketoprofen is designed as a gel, it can avoid the gastrointestinal irritation caused by oral administration, and can also achieve the purpose of local treatment, which can greatly improve the quality of life of patients, and will be welcomed by patients. the

Contents of the invention

In view of the deficiencies in the above-mentioned prior art, the object of the invention is to provide a ketoprofen gel with better stability and therapeutic effect and a preparation method thereof. the

The object of the present invention is achieved through the following technical scheme: the ketoprofen ethanol solution made of ketoprofen and dehydrated alcohol is added to the gel matrix made of polyethylene glycol PEG400, propylene glycol and carbomer 940NF It can be obtained by stirring evenly in the medium; wherein the weight percentages of the above-mentioned raw materials are: ketoprofen 0.02-0.08%: absolute ethanol 15-40%; polyethylene glycol PEG400 40-80%; propylene glycol 10-30%; carbomer 940NFO.5-2%. the

The preparation method is as follows: take 0.02-0.08% of ketoprofen and add 15-40% of absolute ethanol to dissolve it into a ketoprofen ethanol solution for later use; take carbomer 940NFO.5-2% and add polyethylene glycol PEG400 40-80% and 10-30% propylene glycol, heat at 70-80°C and stir to disperse evenly, then add dropwise 5% ethanol solution of triethanolamine, adjust the pH value between 3.0-6.0, and get a transparent gel after stirring evenly Substrate: the above-mentioned standby ketoprofen ethanol solution is gradually added into the gel matrix, and the ketoprofen gel can be made after stirring evenly. the

The advantages of the present invention are that the stability is much better than that of formulations, and it is easy to store and not easy to volatilize. Stability test results prove that the quality of ketoprofen gel is relatively stable, and there is no obvious change in each index (seeing attached table 1). good. It has anti-inflammatory, antipyretic, and analgesic effects; it is used for fever caused by colds, acute upper respiratory infections, and acute pharyngitis; mild and moderate pain; rheumatoid arthritis: rheumatoid arthritis and osteoarthritis The treatment effect of the disease is remarkable, the product. The variety of dosage forms has been enriched, and the market prospect is very broad. ,

The present invention is described below in conjunction with embodiment. the

Detailed ways:

Example 1

Preparation formula: Ketoprofen 2.5g; Dehydrated alcohol 947.5g; Polyethylene glycol PEG400 3000g; Propylene glycol 1000g; Carbomer 940NF 50g; Triethanolamine 5% ethanol solution 10ml. the

Preparation method: Weigh 2.5g of ketoprofen and add 947.5g of absolute ethanol to dissolve it into a ketoprofen ethanol solution for later use; take 50g of Carbomer 940NF, add 3000g of polyethylene glycol PEG400 and 1000g of propylene glycol, heat at 70-80°C and stir to disperse evenly , then dropwise add 10ml of triethanolamine 5% ethanol solution to adjust the pH value to 4.6), after stirring evenly, a transparent gel matrix can be obtained; After stirring evenly, 5000 g of ketoprofen gel can be made, sterilized, rapidly cooled, condensed, and dried to obtain final product. the

Example 2

Preparation formula: ketoprofen 2.5g; absolute ethanol 947.5g; polyethylene glycol PEG400 3000g; propylene glycol 1000g; carbomer 940NF 50g; triethanolamine 5% ethanol solution 10ml. the

Preparation method: Weigh 0.25g of ketoprofen and add 200g of absolute ethanol to dissolve into a ketoprofen ethanol solution for later use; take 10g of Carbomer 940NF, add 580g of polyethylene glycol PEG400 and 207.5g of propylene glycol, heat at 70-80°C and stir to disperse evenly , then dropwise add 20ml of triethanolamine 5% ethanol solution (adjust the pH value to 4.2), and get a transparent gel matrix through stirring; gradually add the above-mentioned standby ketoprofen ethanol solution into the gel matrix , can be made into 1000g of ketoprofen gel after stirring evenly, sterilize, cool down rapidly, condense, and dry to get final product. the

Embodiment 3 ketoprofen gel preliminary stability test

pH measurement: prepare 3 batches of samples with the best prescription, take 2g each in a small beaker, add 50ml of distilled water to prepare a uniform solution, and measure the pH with a pHS-2C acidity meter. the

Centrifugal test: prepare 3 batches of samples with the best prescription, take 5g each, put them in a 10ml centrifuge tube, centrifuge (3000r/min) for 30min, observe the changes in the appearance and spreadability of the gel. the

Heat resistance test: Prepare 3 batches of samples with the best prescription, place them in glass bottles and seal them, put them in an oven at (60±2)°C, take them out after 24 hours, return to room temperature, observe the changes in appearance, spreadability and pH, and Determination of content. the

Cold resistance test: Prepare 3 batches of samples with the best prescription, put them in a glass bottle and seal them, put them in a refrigerator at (-15±2)°C, take them out after 24 hours, return to room temperature, observe the changes in appearance, spreadability and pH, and Determination of content. the

Table 1, ketoprofen gel centrifugation test, heat resistance, cold resistance test and pH test results

As can be seen from the test results, the ketoprofen gel is evenly distributed without delamination or precipitation after the centrifugal test. After being placed at (60±2)°C for 24 hours, the content increased slightly, and the color turned yellow, but there was no layered precipitation, which may be due to impurities in the process, and the specific process needs to be further studied. At (-15 ± 2). During the storage under condition C, the gel becomes ice, but after returning to room temperature for a period of time, it gradually melts, and there is no obvious change in content and color, and there is no stratification or precipitation. It shows that ketoprofen is relatively stable at low temperature. Therefore, we recommend that the ketoprofen gel should be stored at low temperature and avoid high temperature environment as much as possible. the

Embodiment 4 analgesic effect test

The ketoprofen gel of the present invention can significantly reduce the number of mouse writhing times caused by chemical pain-inducing reagents such as acetic acid, and its analgesic effect intensity is similar to that of naproxen. There were 30 Kunming mice, half and half of ♀♂a, Body weight 20 ± 2g, were randomly divided into 3 groups, 10 animals in each group, the abdomen of the animals was depilated, and the exposed skin of 2cm×2cm was the administration area. Blank group is given blank gel matrix 0.4g, and positive control group is given Naproxen ointment 0.4g, and drug group is given ketoprofen gel of the present invention 0.4g. 30 minutes after administration, each mouse was intraperitoneally injected with 0.2 ml of 0.3% glacial acetic acid. The number of times each mouse writhed within 15 minutes after injection was recorded. Compared with the blank group, the inhibition rate of naproxen was 63.07, and the inhibition rate of the ketoprofen gel group of the present invention was 51.11%. 

Table 2, the analgesic effect test result of ketoprofen gel on mice

* indicates p<0.05 compared with the blank group. the

Claims (4)

1. a ketoprofen gel is characterized in that: the ketoprofen ethanol solution made of ketoprofen and dehydrated alcohol is added to the ketoprofen gel made of polyethylene glycol (PEG400), propylene glycol and carbomer 940NF Stir evenly in the gel matrix to obtain: wherein the weight percentages of the above-mentioned raw materials are: ketoprofen 0.02-0.08%; dehydrated alcohol 15-40%; polyethylene glycol (PEG400) 40-80%; propylene glycol 10- 30%; Carbomer 940NF 0.5-2%. 2. the preparation method of ketoprofen gel as claimed in claim 1 is characterized in that: take by weighing ketoprofen 0.02-0.08% and add dehydrated alcohol 15-40% and dissolve into ketoprofen ethanol solution for subsequent use; Get card Bohm 940NF 0.5-2%, add polyethylene glycol (PEG400) 40-80% and propylene glycol 10-30%, heat at 70-80°C and stir to disperse evenly, then add triethanolamine 5% ethanol solution dropwise to adjust the pH value Between 3.0 and 6.0, a transparent gel matrix can be obtained after stirring evenly. 3. ketoprofen gel as claimed in claim 1 is characterized in that: above-mentioned standby ketoprofen ethanol solution is gradually added in the gel matrix, can be made into ketoprofen gel through stirring, sterilization , quickly cool down, condense, dry, that is. 4. ketoprofen gel as claimed in claim 1, is characterized in that: product is semifluid or solid gel.