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

Journal of Pharmaceutical Health Care and Sciences - Tập 9 Số 1
Ginjiro Kato1, Hidemichi Mitome1, Yoshimasa Miyauchi1, Shigetaka Takeda1, Yoshito Toyota1, Noriaki Hidaka2, Mamoru Tanaka2, Kazuki Akira1
1Laboratory of Pharmaceutical Analytical Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-Cho, Matsuyama, Ehime, 790-8578, Japan
2Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan

Tóm tắt

Abstract 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.

Từ khóa


Tài liệu tham khảo

Christmas C, Rogus-Pulia N. Swallowing disorders in the older population. J Am Geriatr Soc. 2019;67:2643–9.

Sestili M, Logrippo S, Cespi M, et al. Potentially inappropriate prescribing of oral solid medications in elderly dysphagic patients. Pharmaceutics. 2018;10:280.

Williams NT. Medication administration through enteral feeding tubes. Am J Health-Syst Pharm. 2008;65:2347–57.

Lau ETL, Steadman KJ, Cichero JAY, Nissen LM. Dosage form modification and oral drug delivery in older people. Adv Drug Deliv Rev. 2018;135:75–84.

Thong MY, Manrique YJ, Steadman KJ. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices. PLoS One. 2018;13:e0193683.

Crul M, Breukels O, Ng S, Le Feber M, Kuijpers E, Smeets O. Limited health risks in performing drug reconstitution and handling tasks in pharmacies - results of an occupational risk assessment study. J Occup Environ Med. 2023;65:e204–10.

Murahashi T, Arai M, Ogata K, Matsumoto M, Higuchi T. Occupational exposure of pharmacists to drugs during tablet crushing and its countermeasures. Fundam Toxicol Sci. 2022;9:85–93.

Kunieda K, Kurata N, Yoshimatsu Y, Ohno T, Shigematsu T, Fujishima I. A safe way to administer drugs through a nutrition tube-the simple suspension method. Dysphagia. 2022;37:318–22.

Tanaka R, Eto D, Goto K, et al. Pharmacokinetic and adsorptive analyses of administration of oral voriconazole suspension via enteral feeding tube in intensive care unit patients. Biol Pharm Bull. 2021;44:737–41.

Morita TO, Yamaguchi A, Kimura S, et al. Stability of lenalidomide suspension after preparation by a simple suspension method for enteral tube administration. J Oncol Pharm Pract. 2016;22:579–83.

Masaoka Y, Kawasaki Y, Kikuoka R, et al. Development of an appropriate simple suspension method for valganciclovir medication. J Pharm Health Care Sci. 2021;6:16.

Mori H, Tack J, Suzuki H. Magnesium oxide in constipation. Nutrients. 2021;13:421.

Kang SJ, Cho YS, Lee TH, et al. Medical management of constipation in elderly patients: systematic review. J Neurogastroenterol Motil. 2021;27:495–512.

Ogawa R, Echizen H. Clinically significant drug interactions with antacids: an update. Drugs. 2011;71:1839–64.

Aoki M, Naya M, Arima S, et al. Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube. J Pharm Health Care Sci. 2021;7:18.

Suryani N, Sugiyama E, Kurata N, Sato H. Stability of ester prodrugs with magnesium oxide using the simple suspension method. Jpn J Pharm Health Care Sci. 2013;39:375–80.

Rossi M, Fabris E, Barbisan D, Massa L, Sinagra G. Lipid-lowering drug therapy: critical approach for implementation in clinical practice. Am J Cardiovasc Drugs. 2022;22:141–55.

Muscoli S, Ifrim M, Russo M, et al. Current options and future perspectives in the treatment of dyslipidemia. J Clin Med. 2022;11:4716.

Khedr A. Stability-indicating high-performance liquid chromatographic assay of atorvastatin with fluorescence detection. J AOAC Int. 2007;90:1547–53.

Chaudhari BG, Patel NM, Shah PB. Stability indicating RP-HPLC method for simultaneous determination of atorvastatin and amlodipine from their combination drug products. Chem Pharm Bull. 2007;55:241–6.

Önal A, Sagirli O. Development of a selective LC method for the determination of pravastatin sodium. Chromatographia. 2006;64:157–62.

Machairas G, Panderi I, Geballa-Koukoula A, et al. Development and validation of a hydrophilic interaction liquid chromatography method for the quantitation of impurities in fixed-dose combination tablets containing rosuvastatin and metformin. Talanta. 2018;183:131–41.

Belal F, Ibrahim F, Khedr A, Elawady T. Stability indicating TLC method for the determination of rosuvastatin and identification of some degradation products using electrospray ionization mass spectrometry. J Liq Chromatogr Relat Technol. 2014;37:1114–32.

Alvarez-Lueje A, Valenzuela C, Squella JA, Núñez-Vergara LJ. Stability study of simvastatin under hydrolytic conditions assessed by liquid chromatography. J AOAC Int. 2005;88:1631–6.

Yang DJ, Hwang LS. Study on the conversion of three natural statins from lactone forms to their corresponding hydroxy acid forms and their determination in Pu-Erh tea. J Chromatogr A. 2006;1119:277–84.

Goel A, Baboota S, Sahni JK, et al. Development and validation of stability-indicating assay method by UPLC for a fixed dose combination of atorvastatin and ezetimibe. J Chromatogr Sci. 2013;51:222–8.

Sánta Z, Kóti J, Szőke K, Vukics K, Szántay C Jr. Structure of the major degradant of ezetimibe. J Pharm Biomed Anal. 2012;58:125–9.

Baťová J, Imramovský A, HájÍček J, Hejtmánková L, Hanusek J. Kinetics and mechanism of the base-catalyzed rearrangement and hydrolysis of ezetimibe. J Pharm Sci. 2014;103:2240–7.

Kato G, Mitome H, Teshima K, et al. Study on the use of ozone water as a chemical decontamination agent for antineoplastic drugs in clinical settings. Ann Work Expo Health. 2023;67:241–51.

Kublin E, Malanowicz E, Kaczmarska-Graczyk B, Czerwińska K, Wyszomirska E, Mazurek AP. Development of chromatographic method for determination of drugs reducing cholesterol level-statins and ezetimibe. Acta Pol Pharm. 2015;72:429–37.

Takano Y, Kabe H, Mizoi K, et al. Effect of magnesium oxide on the stability of ACE inhibitors in simple suspension method. Jpn J Pharm Health Care Sci. 2021;47:208–16.

Russell TL, Berardi RR, Barnett JL, et al. Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women. Pharm Res. 1993;10:187–96.

Martin PD, Schneck DW, Dane AL, Warwick MJ. The effect of a combination antacid preparation containing aluminium hydroxide and magnesium hydroxide on rosuvastatin pharmacokinetics. Curr Med Res Opin. 2008;24:1231–5.

Geboers S, Stappaerts J, Tack J, Annaert P, Augustijns P. In vitro and in vivo investigation of the gastrointestinal behavior of simvastatin. Int J Pharm. 2016;510:296–303.

Hoffmann M, Nowosielski M. DFT study on hydroxy acid-lactone interconversion of statins: the case of atorvastatin. Org Biomol Chem. 2008;6:3527–31.

Thông tin
Thông tin xuất bản

Journal of Pharmaceutical Health Care and Sciences

Tập 9 Số 1

Thông tin tác giả