The Formation of Furfural Compounds in Selected Saccharide- and Polysaccharide-based Pharmaceutical Excipients

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 5; pp. 1811 - 1820
• Main Authors: Douša, Michal, Gibala, Petr, Břicháč, Jiří, Havlíček, Jaroslav
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.05.2012; Wiley Subscription Services, Inc., A Wiley Company; Elsevier; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: 5-hydroxymethyl furfural; analytical chemistry; Biological and medical sciences; Carbohydrates - chemistry; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Chromatography, High Pressure Liquid; Excipients; excipients degradation; formulation; Furaldehyde - chemical synthesis; General pharmacology; HPLC; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Life Sciences & Biomedicine; Limit of Detection; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Polysaccharides - chemistry; Reproducibility of Results; Science & Technology; stability; Temperature; formulation; 5-hydroxymethyl furfural; analytical chemistry; excipients; excipients degradation; HPLC; stability; DEXTROSE; JUICES; LIQUID-CHROMATOGRAPHIC DETERMINATION; 5-HMF; D-FRUCTOSE; MUTAGENICITY; FURAN; 5-hydroxymethylfurfural; DEGRADATION; HPLC DETERMINATION; CELLULOSE; Stability; Pharmaceutical technology; Vehicle(excipient); HPLC chromatography; Degradation; 5-hydroxymethyl-furfural; Formulation; Oside polymer; Carbohydrate; Polysaccharide; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23072

The acid hydrolysis of various selected saccharide- and polysaccharide-based pharmaceutical excipients under acid hydrolysis and the formation of degradation compounds were studied. New degradation products formed from these excipients were discovered. Liquid chromatography–mass spectrometry and nuclear magnetic resonance techniques were employed to identify and fully characterize these unknown compounds. The degradation products were identified as [(5-formylfuran-2-yl)methoxy]acetic acid, 5-[(propan-2-yloxy)methyl]furan-2-carbaldehyde, along with the previously identified 5-(methoxymethyl)furan-2-carbaldehyde. On the basis of the identification of these degradation products, a reasonable mechanism for their formation can be proposed. Temperature and pH affect the hydrolysis rates of saccharides and polysaccharides, which in turn affects the rate of formation of furfural compounds. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1811–1820, 2012