A novel depot preparation of desferrioxamine-B: development of formulation principles.
This report describes the feasibility of simple oil-based depot formulations of a novel n-decanesulfonate salt of the iron chelator desferrioxamine-B. After subcutaneous administration in rodents, desferrioxamine-B n-decanesulfonate depot induces both (a) prolonged release of drug and (b) an increase of at least threefold to fourfold in iron excretion efficiency compared with the parent compound Desferal (desferrioxamine-B mesylate). Optimization experiments probing vehicle composition, surfactant loading, drug loading, and particle size distribution of the depot preparation are described, and the physiochemical stability of an identified pilot formulation is assessed.
Lowther
N
N
Drug Preformulation and Delivery Department, Ciba Pharmaceuticals (now Novartis Horsham Research Center), West Sussex, England. nicholas.lowther@pharma.novartis.com
Sparks
K
K
Nicklin
J
J
Jin
Y
Y
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003676:Deferoxamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D007501:Iron / Q000652:urine; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D051381:Rats; D012212:Rheology
D003692:Delayed-Action Preparations; D005079:Excipients; D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine