title: Characterization and relevance of physicochemical interactions among components of a novel multiparticulate formulation for colonic delivery.
abstract: The primary objective of this study was to investigate potential interactions among a model drug (azathioprine; AZA), polymers and a divalent metal ion, which were utilized in the development of a novel multiparticulate formulation for colonic delivery. The approach involved preparation of beads by ionotropic gelation of deacylated gellan gum (DGG) in the presence of Ca(2+) ions, followed by coating with Eudragit S-100. Various possible physicochemical interactions among formulation components were characterized by DSC, FT-IR, XRPD, (1)H-NMR, and an isothermal stress test. Results of isothermal stress testing indicated that there was no significant interaction of AZA with DGG and Eudragit S-100. However, results of DSC and XRPD studies suggested that there could be interactions between AZA and DGG, and ionotropic gelation can affect the physical state of AZA, which may have implications for drug release characteristics and, physical and chemical stability. The results of FT-IR studies were suggestive of interactions of DGG with AZA and Eudragit S-100, and provided evidence for interactions of AZA and DGG with Ca(2+) ions. The electrostatic interaction of DGG with Ca(2+) was also supported by results of DSC studies while that between AZA and Ca(2+) was confirmed by (1)H-NMR studies. This study, to our knowledge, is first reported investigation in which the unique thermal property of gellan gum gels, and possible interactions between a drug and counter ions of an ionotropic agent have been demonstrated through bead characterization studies. The formation of AZA-Ca(2+) complex could have an impact on drug release kinetics, product stability and clinical efficacy for treatment of inflammatory bowel diseases or other diseases, which merit further investigation.
authors.affiliation: Drug Delivery Systems Research Laboratory, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA. brahmasingh@hotmail.com
authors.forename: Brahma N
authors.initials: BN
authors.lastname: Singh
authors.forename: Kwon H
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism; D001379:Azathioprine / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005765:Gastrointestinal Agents / Q000737:chemistry* / Q000378:metabolism; D005782:Gels; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005765:Gastrointestinal Agents; D005782:Gels; D011109:Polymethacrylic Acids; D011135:Polysaccharides, Bacterial; C038300:methylmethacrylate-methacrylic acid copolymer; C048288:gellan gum; D001379:Azathioprine; D002118:Calcium