Physicochemical and toxicological characterization of sucrose-bound polynuclear iron oxyhydroxide formulations
- 218 Downloads
Intravenous iron formulations comprising of iron/iron–oxyhydroxide–carbohydrate complex are an established therapy for the treatment of iron deficiency anemia. These preparations should be subjected to exhaustive physicochemical and toxicological studies in order to establish their safety and efficacy. Following Venofer® (innovator iron–sucrose formulation), various iron sucrose similar have entered into the market with equivalent physicochemical and toxicological profile. This report describes the physicochemical and toxicological studies of a novel iron sucrose injection (IS-Claris). IS-Claris and Venofer® were subjected to various physicochemical studies such as elemental and chemical analysis; X-ray diffraction; particle size and distribution; labile iron detection, Mössbauer and Raman spectroscopy. The presence of iron oxides in IS-Claris and Venofer® could be confirmed by the major peaks at 24.65° (2θ) and 38.2° (2θ). The iron sucrose samples demonstrated similar reduction peaks of Fe(III) to Fe in their respective polarograms. The average diameter of the core of IS-Claris and Venofer® was estimated to be 2.92 ± 0.01 and 2.77 ± 0.63 nm, respectively. The Mössbauer spectra of IS-Claris and Venofer® showed a doublet with an isomer shift δ = 0.43 ± 0.01 mm/s. Moreover, the other physicochemical specifications of IS-Claris were comparable to Venofer®. The toxicological studies demonstrated that IS-Claris safety profile is equivalent to Venofer®. It could be concluded that IS-Claris could be used as a potential alternative to Venofer® with similar clinical implications.
KeywordsIron–sucrose complex Venofer® X-ray diffractometry Raman spectroscopy Labile iron Toxicology
All authors (B.S. Barot, P.B. Parejiya, P.K. Shelat, G.B. Shah, D.M. Mehta, and T.V. Pathak) declare that they have no conflict of interest. The authors are thankful to Mrs. Mallika Babu and Ms. Sona Chaudhri for providing a helping hand in the preparation of manuscript.
- Binner JGP, Santacruz MI, Annapoorani K (2009) Method for concentrating nanosuspensions. US Patent US 2009/0294357 A1Google Scholar
- Breymann C, Bian XM, Blanco-Capito LR, Chong C, Mahmud G, Rehman R (2011) Expert recommendations for the diagnosis and treatment of iron-deficiency anemia during pregnancy and the postpartum period in the Asia-Pacific region. J Perinat Med 39(2):113–121. doi: 10.1515/JPM.2010.132 PubMedGoogle Scholar
- Funk F, Long GJ, Hautot D, Büchi R, Christl I, Weidler PG (2001) Physical and chemical characterization of therapeutic iron containing materials: a study of several superparamagnetic drug formulations with the β-FeOOH or ferrihydrite structure. Hyperfine Interact 136–137(1–2):73–95. doi: 10.1023/a:1015552311359 CrossRefGoogle Scholar
- Futterer S, Andrusenko I, Kolb U, Hofmeister W, Langguth P (2013) Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X-ray powder diffraction (XRPD). J Pharm Biomed Anal 86:151–160. doi: 10.1016/j.jpba.2013.08.005 CrossRefPubMedGoogle Scholar
- Garcia-Erce JA, Cuenca J, Martinez F, Cardona R, Perez-Serrano L, Munoz M (2006) Perioperative intravenous iron preserves iron stores and may hasten the recovery from post-operative anaemia after knee replacement surgery. Transfus Med 16(5):335–341. doi: 10.1111/j.1365-3148.2006.00682.x CrossRefPubMedGoogle Scholar
- Jahn MR, Andreasen HB, Futterer S, Nawroth T, Schunemann V, Kolb U, Hofmeister W, Munoz M, Bock K, Meldal M, Langguth P (2011) A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm 78(3):480–491. doi: 10.1016/j.ejpb.2011.03.016 CrossRefPubMedGoogle Scholar
- NICE-guidelines (2008) Chronic kidney disease—national clinical guidelines for early identification and management in adults in primary and secondary care. National Institute of Health and Clinical Excellence, LondonGoogle Scholar
- Toblli JE, Cao G, Oliveri L, Angerosa M (2009b) Differences between the original iron sucrose complex Venofer® and the iron sucrose similar Generis®, and potential implications. Port J Nephrol Hypertens 23(1):53–63Google Scholar
- USFDA (2000) Pharmacology review of NDA for Venofer®. Center for Drug Evaluation and Research Application No 21-135Google Scholar
- USP (2006) Iron sucrose injection monograph, 29 ed. United States Pharmacopeia 29-National Formulary 24, USP Convention, RockvilleGoogle Scholar