Use of compounded dispersing media for extemporaneous pediatric syrups with candesartan cilexetil and valsartan

Monika Musko 1 , 2  und Malgorzata Sznitowska 3
  • 1 Department of Pharmaceutical Technology, Medical University of Bialystok, Faculty of Pharmacy Bialystok, Poland
  • 2 Department of Clinical Pharmacy Medical University of Bialystok Faculty of Pharmacy, Bialystok, Poland
  • 3 Department of Pharmaceutical Technology, Medical University of Gdansk, Faculty of Pharmacy Gdansk, Poland

Abstract

Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL-1) and valsartan (4 mg mL-1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 - with xanthan gum (0.5 %), V2 - the USP/NF vehicle for oral solution and V3 - the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 °C. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the 14-day expiry date was not achieved because of microbial deterioration.

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  • 1. EMA/428172/2012. European Medicines Agency with its Paediatric Committee. 5-year Report to the European Commission. General report on the experience acquired as a result of the application of the Paediatric Regulation; http://ec.europa.eu/health/files/paediatrics/2012-09_pediatric_report-annex1-2_en.pdf; access date October 28, 2014.

  • 2. F. Brion, A. J. Nunn and A. Rieutord, Extemporaneous (magistral) preparation of oral medicines for children in European hospitals, Acta Paediatr. 92 (2003) 486-490.

  • 3. J. Hempenstall and C. Tuleu, Formulating better medicines for children, Int. J. Pharm. 379 (2009) 143-145; DOI: 10.1016/j.ijpharm.2009.06.033.

  • 4. Atacand (Candesartan Cilexetil) Drug Information: Description, User Reviews, Drug Side Effects, Interactions - Prescribing Information at RxList; http://www.rxlist.com/atacand-drug.htm; access date October 28, 2014.

  • 5. Atacand. Patient Information approved by the U.S. Food and Drug Administration, 2013; http:// www1.astrazeneca-us.com/pi/Atacand.pdf; access date October 28, 2014.

  • 6. Diovan (Valsartan) Drug Information: Description, User Reviews, Drug Side Effects, Interactions - Prescribing Information at RxList; http://www.rxlist.com/diovan-drug.htm; access date October 28, 2014.

  • 7. Diovan. Patient Information approved by the U.S. Food and Drug Administration, 2012; http:// www.pharma.us.novartis.com/product/pi/pdf/diovan.pdf; access date October 28, 2014.

  • 8. G. N. Darwhekar and D. K. Jain, Biopharmaceutical classification of candesartan and candesartan cilexetil, Asian J. Pharm. Life Sci. 2 (2012) 295-302.

  • 9. J. Liu, I. R. Younis, K. R. Madabushi and P. R. Jadmav. Office of Clinical Pharmacology Review. NDA 20-838 Review - candesartan; http://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/ucm189128.pdf; access date October 28, 2014.

  • 10. M. Saydam and S. Takka, Bioavailability file: valsartan, Fabad J. Pharm. Sci. 32 (2007) 185-196.

  • 11. P. Tosco, B. Rolando, R. Frottero, Y. Henchoz, S. Martel, P. A. Carrput and A. Gasco, Physiochemical profiling of sartans: a detailed study of ionization constants and distribution coefficients, Helv. Chim. Acta. 91 (2008) 468-482; DOI: 10.1002/hlca.200890051.

  • 12. F. Schaefer, J. van de Walle, A. Zurowska, C. Gimpel, K. van Hoeck, D. Drozd, G. Montini, I.V. Bagdasorova, J. Sorof, J., Sugg, R. Teng and J. W. Hainer, Efficiency, safety and pharmacokinetics of candesartan cilexetil in hypertensive children from 1 to less than 6 years of age, J. Hypertens. 28 (2010) 1083-1090; DOI: 10.1097/HJH.0b013e328336b86b.

  • 13. F. Schaefer, R. Coppo, A. Bagga, P. Senquttuvan, R. Schlosshauer, Y. Zhang and M. Kadwa, Efficacy and safety of valsartan in hypertensive children 6 months to 5 years of age, J. Hypertens. 31 (2013) 993-1000; DOI: 10.1097/HJH.0b013e32835f5721.

  • 14. J. Hempenstall and C. Tuleu, Meeting commentary - Formulating better medicines for children, Int. J. Pharm. 379 (2009) 143-142; DOI: 10.1016/j.ijpharm.2009.06.033.

  • 15. Ora® Products Data Sheets; http://www.perrigo.com/business/prodsearch.aspx?group=paddock; access date October 28, 2014.

  • 16. M. C. Nahata and V. A. Loyd, Extemporaneous drug formulations, Clin. Ther. 30 (2008) 2112-2119; DOI: 10.1016/j.clinthera.2008.11.020.

  • 17. USP/NF 36/31. United States Pharmacopeia 2012, The United States Pharmacopeial Convention 1206, Rockville 2012, pp. 1958; 1964; 2116; 2118; 2262.

  • 18. S. M. El-Gizawy, O. H. Abdelmageed, M. A. Omar, S. M. Deryea and A. M. Abdel-Megied, Development and validation of HPLC method for simultaneous determination of amlodipine, valsartan hydrochlorothiazide in dosage form and spiked human plasma, Am. J. Anal. Chem. 3 (2012) 422-430; DOI: 10.4236/ajac.2012.36055.

  • 19. B. M. Sudesh and K. S. Uttamrao, Determination and validation of valsartan and its degradation products by isocratic HPLC, J. Chem. Metrl. 3 (2009) 1-12.

  • 20. M. Pérez, G. Ramírez, M. Pérez and P. Restrepo, Validation of an analytical method for the determination of valsartan in human plasma by HPLC/UV with addition standard using losartan as an internal standard, Colomb. Med. 38 (2007) 13-20.

  • 21. K. Hoppe, M. Sznitowska, The effect of polysorbate 20 on solubility and stability of candesartan cilexetil in dissolution media, AAPS PharmSciTech. (in press, accepted March 6, 2014).

  • 22. G. Lunn, HPLC Methods for Recently Approved Pharmaceuticals, John Wiley & Sons Inc., Hoboken, New Jersey, 2005, p. 104; 671.

  • 23. S. S. Chitlange, K. Bagri and D. M. Sakarkar, Stability indicating RP- HPLC Method for simultaneous estimation of valsartan and amlodipine in capsule formulation, Asian J. Research Chem. 1 (2008) 15-18.

  • 24. S. K. Patro, S. K. Kanungo, V. J. Patro and N. S. K. Choudhury, Stability indicating RP-HPLC method for determination of valsartan in pure and pharmaceutical formulation, E-J. Chem. 7 (2010) 246-252; DOI: 10.1155/2010/487197.

  • 25. V. A. Loyd, Stability of extemporaneously prepared oral liquid formulations - part VI, Secundum Artem 15 (2008); http://www.perrigo.com/business/pdfs/Sec%20Artem%2015.1.pdf; access date October 28, 2014.

  • 26. V. A. Loyd, Valsartan 4 mg mL-1 oral liquid, Int. J. Pharmac. Compd. 12 (2008) 269.

  • 27. N. Siddiqui, A. Husain, L. Chaudhry, A. M. Shamsher, M. Mitra and P. S. Bhasin, Pharmacological and pharmaceutical profile of valsartan: a review, J. App. Pharm. Sci. 1 (2011) 12-19.

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