What Factors Affect Naproxen Dosage?

Naproxen sodium has tablets and capsules, which are antipyretic, anti-inflammatory and analgesic drugs. This product is a non-steroidal anti-inflammatory drug. Suitable for all kinds of mild to moderate pain, such as pain after tooth extraction and other operations, primary dysmenorrhea and headache. It is also suitable for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, juvenilearthritis, tendonitis, bursitis, and acute gouty arthritis. It has pain, swelling and limited mobility for arthritis. It can relieve symptoms.

Naproxen sodium

Naproxen sodium has tablets and capsules, which are antipyretic, anti-inflammatory and analgesic drugs. This product is a non-steroidal anti-inflammatory drug. Suitable for all kinds of mild to moderate pain, such as pain after tooth extraction and other operations, primary dysmenorrhea and headache. It is also suitable for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, juvenilearthritis, tendonitis, bursitis, and acute gouty arthritis. It has pain, swelling and limited mobility for arthritis. It can relieve symptoms.

Drug Name

Naproxen sodium

Foreign name

Naproxen Sodium

Pinyin name

Naipushengna

Page number

2000 Edition Part Two -762

[Molecular formula] C14H13NaO3 252.25

This product is sodium -methyl-6-methoxy-2-naphthalene acetate. Calculated on dry basis, C14H13NaO3 should be 98.0% 102.0%.

[Properties] Ben Lu is a white or off-white crystalline powder; odorless; slightly hygroscopic.

This product is easily soluble in water, soluble in methanol, slightly soluble in ethanol, and slightly soluble in acetone. It is almost insoluble in chloroform or toluene.

Take the specific rotation of 0.5g, add 6ml of water, dropwise add 1ml / L hydrochloric acid solution 2.4ml, shake while adding dropwise, after the precipitate is precipitated, wash the precipitate to neutral with water, dry at 105 ° C to constant weight, accurately weigh , Add chloroform to make a solution containing 10mg per 1ml. Determined according to law (Appendix VI E), the specific rotation is + 63 ° to + 69 °.

[Category] Antipyretic anti-inflammatory analgesics.

[Storage] shading, sealed, and stored in a dry place.

preparation

[Identification] (1) Take about 0.1g of this product, add 2ml of water to dissolve it, add a few drops of dilute hydrochloric acid, and a white precipitate will occur. After filtration, the filtrate will identify the sodium salt (Appendix III).

(2) After taking this product and drying it at 105 ° C for 3 hours, its infrared absorption spectrum should be the same as that of the control (spectrum set 433).

[Inspection] Take this product and add methanol to make a solution containing 20mg per 1ml as the test solution; take a precise amount and dilute with methanol to a solution containing 0.1mg per 1ml as the control solution; According to the thin layer chromatography (Appendix V B) test, take 10 l of each of the two solutions, point them on the same silica gel GF254 thin-layer plate, and use toluene-tetrahydrofuran-glacial acetic acid (30: 3: 1) as the developing agent. After that, let it dry and inspect under an ultraviolet light (254nm). If the solution of the test product shows impurity spots, its fluorescence intensity should not be stronger than the main spot of the control solution.

Take 5.0g of free naproxen, weigh it accurately, place in a separatory funnel, add 25ml of water to dissolve, shake with chloroform for 3 times, 15ml each time, combine the chloroform solution, place on a water bath and evaporate the residue, use 75 Neutral methanol (neutral to phenolphthalein indicator solution) is dissolved in 50ml, 3 drops of phenolphthalein indicator solution are added, titration with sodium hydroxide titration solution (0.1mol / L), consumption of sodium hydroxide titration solution (0.1mol / L) shall not be used. Hub 2.2ml (1.0%).

Take the product after losing weight and dry it at 105 to constant weight. The weight loss should not exceed 1.0% (Appendix L).

Take 1.0 g of the heavy metal, place it in a separating funnel, add 20 ml of water to dissolve, add 1 mol / L hydrochloric acid solution 5 ml, and extract 3 times with chloroform (20 ml, 20 ml, and 10 ml). Discard the dichloromethane layer and the water layer. In accordance with the law (Appendix H, the first method), the content of heavy metals must not exceed 20 parts per million.

[Content determination] Take about 0.2g of this product, accurately weigh, add 30ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titration solution (0.1mol / L) until the solution is blue-green, and The results of the titration were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 25.22mg of C14H13NaO3.

Method name:

Determination of Naproxen Sodium-Neutralization Titration

Application:

This method uses a titration method to determine the content of naproxen sodium.

This method is applicable to naproxen sodium.

Method principle:

After the test product was dissolved by adding glacial acetic acid, a crystal violet indicator solution was added, and the solution was titrated with a perchloric acid titrant (0.1 mol / L) until the solution was blue-green. The amount of perchloric acid titrant was recorded and calculated.

Reagent:

1. Water (newly boiled to room temperature)

2. Perchloric acid titrant (0.1mol / L)

3. Crystal violet indicator liquid

Glacial acetic acid

5. Reference potassium phthalate

equipment:

Sample preparation:

1. Perchloric acid titrant (0.1mol / L)

Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL acetic anhydride per 1g of water), add 8.5mL perchloric acid (70% -72%), shake well, and slowly add acetic anhydride dropwise at room temperature. 23mL, shake while adding, shake evenly after adding, let cool, add an appropriate amount of anhydrous glacial acetic acid to 1000mL, shake well, and leave for 24 hours. If the test sample is easily acetylated, the water content on this page must be determined by moisture measurement, and then the water content of this solution should be adjusted to 0.01% -0.2% with water and acetic anhydride.

Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and titrate slowly with Blue, and the results of the titration are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.

Storage: Place in a brown glass bottle and keep tightly closed.

Crystal violet indicator liquid

Take 0.5g of crystal violet and add 100mL of glacial acetic acid to dissolve.

Steps:

Accurately weigh 0.2g of this product, add 30mL of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate the solution blue-green with perchloric acid titrant (0.1mol / L), and correct the titration result with a blank test. Record the volume of perchloric acid titrant consumed (mL). Each 1mL of perchloric acid titrant (0.1mol / L) is equivalent to 25.22mg of naproxen sodium (C14H13NaO3), that is, obtained.

Note 1: "Precise weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision weighing" means that the accuracy of the measured volume should conform to the national standard for the volume of the pipette. Precision requirements.

references:

Pharmacopoeia of the People's Republic of China, compiled by the National Pharmacopoeia Committee, Chemical Industry Press, 2005 edition, Part Two, p.648.

Naproxen has a dose-dependent anti-inflammatory analgesic and antipyretic effect. The intensity of anti-inflammatory effect is about 11 times that of the equivalent dose of Butaxone, and the analgesic and antipyretic effects are 7 times and 22 times that of aspirin. Anti-inflammatory, analgesic, and antipyretic effects are equivalent to indomethacin. The mechanism of action is that naproxen has an effect by inhibiting COX activity and thereby inhibiting PG synthesis, but has a stronger selective inhibitory effect on COX2, so its anti-inflammatory effect is strong, and gastrointestinal side effects are small.

The application equivalent of naproxen free acid and sodium salt is 1: 1.1. After oral administration, it is easily absorbed from the gastrointestinal tract and is complete, but its sodium salt absorption rate is faster. After taking the drug for 1 hour, it will reach the peak plasma concentration, and the free acid will take 2 hours. Stomach contents can prolong its absorption time without affecting its absorption rate. High plasma protein binding rate (> 99.5%). It can be distributed in the whole body tissues, and the synovial fluid can reach an effective concentration, and can enter the fetus through the placenta. It is metabolized by the liver and excreted by the kidneys. Most of the excreta are metabolites with a small amount of prototype. About 3% is excreted from feces and 1% is secreted from milk. Plasma t1 / 2 was 13 hours. The product can also be administered rectally, but the absorption rate is slower than oral.

This product is a non-steroidal anti-inflammatory drug. Suitable for all kinds of mild to moderate pain, such as pain after tooth extraction and other operations, primary dysmenorrhea and headache. It is also suitable for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, juvenilearthritis, tendonitis, bursitis, and acute gouty arthritis. It has pain, swelling and limited mobility for arthritis. It can relieve symptoms. Compared with aspirin and indomethacin, the effect of symptom relief was similar, but the incidence and severity of adverse reactions in the gastrointestinal tract and nervous system were lower.

1. Oral doses commonly used by adults.

(1) Resistant to rheumatism, 0.25g to 0.5g at a time, once a day in the morning and evening, or 0.25g in the morning and 0.5g in the evening;

(2) Pain relief, 0.5g for the first time after 0.5g, and once every 6 to 8 hours if necessary;

(3) Acute onset of gouty arthritis, 0.7g for the first time, 0.25g for the next time, every 8 hours, until the acute attack ceases;

(4) Dysmenorrhea, 0.5g for the first time, and 0.25g if necessary later, once every 6 to 8 hours, until the acute attack ceases;

1. Itchy skin, shortness of breath, dyspnea, asthma, tinnitus, lower limb edema, burning sensation, indigestion, stomach pain or discomfort, constipation, dizziness, drowsiness, headache, nausea and vomiting, the incidence is generally 3% to 9 %.

2, blurred vision or visual impairment, hearing loss, diarrhea, oral irritation or pain, palpitation and sweating, etc., the incidence rate of 1% to 3%.

3. Gastrointestinal bleeding, kidney damage (allergic nephritis, pain, renal papillary necrosis and renal failure, etc.), urticaria, allergic rash, mental depression, muscle weakness, hemorrhage or granulocytopenia, and liver function damage. Rare, the incidence is 1% to 3%.

[Contraindications] It is forbidden to use for those who are allergic to aspirin, and caution for those with a history of peptic ulcer or peptic ulcer.

1. Cross-allergies. People who are allergic to aspirin or other non-steroidal anti-inflammatory drugs are also allergic to this product.

2. The research on the effects of this product on the fetus is not enough. Because other non-steroidal anti-inflammatory drugs can cause the fetal arterial duct to close prematurely, and it can inhibit the prostaglandin synthesis and cause dystocia or prolonged labor. Therefore, unless otherwise, pregnant women Not suitable for application.

3. The concentration of this product secreted into milk is equivalent to 1% of the blood drug concentration. It is not suitable for lactating women.

4. Interference to diagnosis: It can affect the determination of 5-hydroxyindole acetate (5-HIAA) and 17-one in urine.

5. The following conditions should be used with caution: when there is a coagulation mechanism or platelet dysfunction, asthma, heart dysfunction or hypertension, liver and kidney dysfunction, active gastrointestinal bleeding or active peptic ulcer and the elderly.

6, long-term medication should be regularly performed liver, kidney function, blood and eye examination.

7. Probenecid, when combined with this product, can enhance the plasma level of this product and prolong the plasma half-life of this product.

[Medication for pregnant and lactating women] Banned

[Children's medication] Anti-rheumatic commonly used in children, 10mg / kg daily, divided into 2 doses.

[Medication for elderly patients]

medicine interactions

1. When drinking alcohol or using it with other anti-inflammatory drugs, adverse reactions in the gastrointestinal tract increase, and there is a risk of ulcers.

2. When used with anticoagulants such as heparin and dicoumarin, bleeding time is prolonged, bleeding tendency may occur, and it may cause gastrointestinal ulcers.

3. When used together with aspirin or other salicylic acid preparations, there is no synergistic effect on symptomatic relief, but instead it increases gastrointestinal adverse reactions.

4. This product can reduce sodium excretion and hypotensive effect of furosemide.

5. This product can inhibit the excretion of lithium with the urine, and increase the plasma concentration of lithium.

6. When used with probenecid, the blood concentration of this product increases, and t1 / 2 is prolonged, which can increase the efficacy, but the toxic response is also increased accordingly, so it is not recommended for clinical use without practical value.

2010 Chinese Pharmacopoeia

Naproxen sodium

Naipushengna

Naproxen Sodium

Page number: 2005 Part Two of Chinese Pharmacopoeia -648

[Updated]

(2) Take the precipitate under identification (1), wash with water to neutrality, dry at 105 ° C for 1 hour, take about 30mg of fine powder, add methanol to make a solution containing 30g per 1ml, and irradiate with UV-visible spectrophotometry Spectrophotometry (Appendix IV A) has maximum absorption at wavelengths of 262nm, 271nm, 317nm, and 331nm.