What is Esomeprazole sodium?

Esomeprazole sodium is used to treat symptoms of gastroesophageal reflux disease (GERD) and other conditions involving excessive stomach acid such as Zollinger-Ellison syndrome. Esomeprazole sodium is also used to promote healing of erosive esophagitis (damage to your esophagus caused by stomach acid).Esomeprazole sodium may also be given to prevent gastric ulcer caused by infection with Helicobacter pylori (H. pylori), or by the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Esomeprazole sodium is not for immediate relief of heartburn symptoms. Esomeprazole sodium may also be used for purposes not listed in this medication guide.[1]

Preparation method of esomeprazole sodium

The preparation method of esomeprazole sodium includes the following steps:1) A mixture of 630 g (2 mol) of omeprazole sulfide and a compound represented by the formula M, The inorganic metal salt was mixed in 5 L of acetone, The mixing conditions are: Temperature 50 ,Stirred for 0.5 hour, Wherein the molar ratio of the omeprazole sulfide to the compound represented by the formula M, the inorganic metal salt is 1: 0.55: 0.1, and the inorganic metal salt is CoSO4.2) At a temperature of 45 ° C,30% H2O2 was added dropwise to the mixture A of step 1) to carry out an oxidation reaction, After completion of the reaction, a solution of sodium hydroxide in methanol was added, The molar ratio of 30% H2O2 to omeprazole sulfide is 1.8; the amount of the solution of sodium hydroxide in methanol is added, in terms of sodium hydroxide, to the amount of omeprazole sulfide Was 1.6.3) a process of purifying the obtained esomeprazole sodium, Refining process includes: First esomeprazole sodium dissolved in 65 ° C in 1.5L acetonitrile, Then 6L of petroleum ether was added dropwise, The temperature was lowered to 40 ° C at a rate of 0.02 ° C / s, and then cooled to 10 ° C at a rate of 0.15 ° C / s, allowed to stand for 1 hour, centrifuged and filtered to obtain 601.4 g of purified esomeprazole sodium, Yield: 85.1%The purity was 99.97% by HPLC, no isomer and excessive oxidation to sulfone impurities. immediate-release formulation containing esomeprazole 20 mg/sodium bicarbonate 800 mg in healthy adult male.[2]

How should I take Esomeprazole sodium?

Use exactly as directed on the label, or as prescribed by your doctor. Take each dose with a full glass (8 ounces) of water. Esomeprazole sodium should be taken at least one hour before a meal. Swallow the pill whole and do not crush, chew, break, or open it. If you cannot swallow a capsule whole, open it and sprinkle the medicine into a spoonful of pudding or applesauce. Swallow the mixture right away without chewing. Do not save it for later use. The Esomeprazole sodium capsule can be given through a nasogastric (NG) feeding tube. Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions. Esomeprazole sodium is usually given for 4 to 8 weeks only. Your doctor may recommend a second course of treatment if you need additional healing time. Use Esomeprazole sodium for the full prescribed length of time, even if your symptoms quickly improve. Call your doctor if your symptoms do not improve or if they get worse while you are taking this medicine. This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using Esomeprazole sodium. Some conditions are treated with a combination of Esomeprazole sodium and antibiotics. Use all medications as directed. Store at room temperature away from moisture and heat.

Study of immediate-release formulation containing Esomeprazole sodium sodium

Esomeprazole sodium is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing Esomeprazole sodium 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed. Proton pump inhibitors (PPIs) are widely used for the treatment of GERD, and they act by suppressing gastric acid secretion and raising intragastric pH. Esomeprazole sodium is one of the most frequently prescribed PPI and provides more rapid and effective relief than other PPIs. However, Esomeprazole sodium is prone to degradation by gastric acid in the stomach. To overcome this shortcoming and protect it from rapid degradation, Esomeprazole sodium was improved via enteric coating. The enteric-coated formulation of Esomeprazole sodium enhanced the stability of active ingredients in the stomach; however, it also led to delayed absorption and onset of action.[3]

Some studies have indicated that a single dose might not be sufficient to achieve maximum effectiveness due to delayed absorption of enteric-coated Esomeprazole sodium. Esomeprazole sodium with enteric coating showed therapeutic efficacy of approximately 68.3% after 8 weeks of treatment; however, the efficacy was about 45.3% after single dose. Despite remarkable effects with respect to the management of GERD, lack of an immediate response might contribute to patient dissatisfaction with treatment and could lead to unnecessary increases in dosage or inappropriate switching to alternate members of this class. The sodium bicarbonate is a chemical compound which can be used as an antacid. It raises the pH of the stomach and creates a chemical umbrella that protects the Esomeprazole sodium and allows it to pass safely to the duodenum where it is absorbed. An immediate-release (IR) formulation containing Esomeprazole sodium 20 mg and sodium bicarbonate 800 mg (IR-ESO; Chong Kun Dang Pharmaceutical Corp., Seoul, Korea) was developed to mitigate the delayed onset of action. This study was designed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of IR-ESO with those of an enteric-coated formulation of Esomeprazole sodium. The details of PK parameters of Esomeprazole sodium in each group are summarized. After single or multiple administrations, the plasma concentration of Esomeprazole sodium in the test group showed a rapid increase, while those in the reference group increased gradually. Median Tmax of Esomeprazole sodium for the test group was shorter than that for the reference group upon both single and multiple administrations. The Tmax was 0.50 hr and 0.75 hr for the test group after single and multiple administrations, respectively, while the values were 1.50 and 1.25 hr for the reference group in each administration. This randomized, open-label, multiple-dose study compared the PK and PD of Esomeprazole sodium between IR-ESO and a tablet of enteric-coated Esomeprazole sodium 20 mg in healthy male subjects. In this study, the two drugs showed similar PK and PD profiles, indicating that the two drugs have a similar extent of absorption and acid inhibitory effects.

Esomeprazole sodium, the S-isomer of omeprazole, is widely used for the treatment of acid-related disorders. In previous studies, Esomeprazole sodium showed more efficacy in maintaining the intragastric pH and exhibited greater inhibition of gastric acid secretion compared to omeprazole. To ensure its stability in the stomach, like other PPIs, Esomeprazole sodium was also developed to a delayed-release enteric coating formulation. However, the enteric-coated Esomeprazole sodium delayed the onset time of therapeutic effect due to delayed absorption. Therefore, IR-ESO was developed to overcome this limitation of delayed onset, to facilitate a rapid effect. The first time to reach pH >4 after single and multiple administrations was faster in the IR-ESO group than in the enteric-coated Esomeprazole sodium group. The pH profiling within 2 hrs after each drug administration showed that pH increased abruptly after IR-ESO administration, but after the administration of enteric-coated Esomeprazole sodium, the pH was maintained around 2, and then increased after breakfast. This rapid pH increase by IR-ESO might be due to the immediate release of Esomeprazole sodium. In addition, sodium bicarbonate acts as a buffer to protect Esomeprazole sodium from gastric acid degradation, and it stimulates the temporary release of gastrin. The increase in gastrin levels allows parietal cells to absorb Esomeprazole sodium before degradation by the gastric acid. In addition, sodium bicarbonate acts as an antacid and rapidly neutralizes gastric acid and may provide faster symptomatic relief independent of accelerated Esomeprazole sodium effect. This IR Esomeprazole sodium formulation with sodium bicarbonate may have an advantage of relieving symptoms rapidly and efficiently in acid-related disorders.

References

[1] Castell DO, Kahrilas PJ, Richter JE, et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol. 2002;97(3):575.

[2] Richter JE, Kahrilas PJ, Johanson J, et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol. 2001;96(3):656–665.

[3] Lind T, Rydberg L, Kyleb?ck A, et al. Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000;14(7):861–867.