Stability of Ester Prodrugs with Magnesium Oxide Using the Simple Suspension Method

Suryani, Nelly; Sugiyama, Erika; Kurata, Nori; Sato, Hitoshi

doi:10.5649/jjphcs.39.375

Cited by 8 publications

(3 citation statements)

References 15 publications

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“…Aoki et al [ 15 ] reported that no degradation occurred in the co-suspension of MgO and clopidogrel bisulfate, which has an ester moiety. On the contrary, Suryani et al [ 16 ] reported that when ester prodrugs, acemetacin and cefpodoxime proxetil, were subjected to the SSM with MgO, the ester bonds were hydrolyzed. These chemical changes were considered to be serious because of the potential occurrence of gastrointestinal injury or some reduction of drug efficacy.…”

Section: Introductionmentioning

confidence: 99%

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide

Kato,

Mitome,

Miyauchi

et al. 2023

J Pharm Health Care Sci

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Background Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan. Methods A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation. Results In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively. Conclusions A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.

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Section: Introductionmentioning

confidence: 99%

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide

Kato,

Mitome,

Miyauchi

et al. 2023

J Pharm Health Care Sci

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show abstract

“…Previous studies have reported the stability of drugs by examining the changes following simultaneous suspension with alkaline drugs, such as magnesium oxide (MgO), or under pH-altered conditions [ 4 – 8 ]. Therefore, when multiple drugs are suspended together, attention should be paid to the suspension pH and changes after mixing.…”

Section: Introductionmentioning

confidence: 99%

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube

Aoki

Naya

Arima

et al. 2021

J Pharm Health Care Sci

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Background In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube. Methods The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction. Results The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone. Conclusions The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

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“…Yano et al 8) confirmed that 8 types of suspended drugs, including phenytoin and digoxin, were found to be stable. Suryani et al 9) demonstrated that suspended ester prodrugs (acemetacin, cefpodoxime proxetil)…”

Section: Introductionmentioning

confidence: 99%

Solubility Estimation for Drugs Treated with the Simple Suspension Method Using Available Dissolution Test Profiles

Sakurada

Shimoyama

Itoh

et al. 2015

Jpn. J. Pharm. Health Care Sci.

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The simple suspension method (SSM) is a method of administering drugs via feeding or gastrostomy tubes to those who have difficulty swallowing. In the SSM, solid formulations (eg, tablets, capsules) are immersed in hot (55℃) water. This promotes the disintegration and dissolution of the drugs and changes their solubility. However, pharmaceutical companies have not issued test results on the solubility and dissolution behaviors of suspended drugs prepared according to the SSM. For this study, we chose 10 drugs, 8 listed and 2 not listed in the Japanese Orange Book, to compare the dissolution behaviors of each drug, treated vs untreated with the SSM. Dissolution was classified into three patterns: rapid (gliclazide and famotidine), moderate (propranolol, pindolol, metoprolol), and slow (furosemide, ibuprofen, glimepiride). The initial dissolution rates of the moderate-dissolution drugs increased markedly by employing the SSM. In this study, hydroxyzine capsules and phenytoin tablets, neither of which is listed in the Japanese Orange Book, were compared with different dosage/administration forms of those drugs listed in the book (ie hydroxyzine tablets and phenytoinphenobarbital combination tablets).

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Stability of Ester Prodrugs with Magnesium Oxide Using the Simple Suspension Method

Cited by 8 publications

References 15 publications

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube

Solubility Estimation for Drugs Treated with the Simple Suspension Method Using Available Dissolution Test Profiles

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