title: Preparation of injectable auto-forming alginate gel containing simvastatin with amorphous calcium phosphate as a controlled release medium and their therapeutic effect in osteoporosis model rat.
abstract: Highly soluble amorphous calcium phosphate powder (ACP) was added to the alginate gel as a buffering agent, in an attempt to enable widely controlled release while avoiding an acidification of the gel-environment. Therapeutic effects of the ACP-containing alginate gel which slowly releases a drug, simvastatin, on osteoporosis model rats were examined. A model drug, simvastatin, incorporated in the alginate gel with ACP up to 0.5%, was continuously released for a long time under the acidic condition. The release rate was controlled by the amount of ACP, serving as a buffer to suppress acidity. When the alginate solution intramuscularly injected in the rat, a soft gel was formed in the injected site. Simvastatin released from the gel containing 0.5% of ACP showed high therapeutic effect on osteoporosis rat. Thus, the present injectable long-sustained release system is expected to be a novel drug delivery controlling device.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ito
authors.forename: Mami
authors.initials: M
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Uchino
authors.forename: Mamoru
authors.initials: M
authors.lastname: Senna
authors.forename: Michele
authors.initials: M
authors.lastname: Iafisco
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: Lia
authors.initials: L
authors.lastname: Rimondini
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D002021:Buffers; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000737:chemistry; D002384:Catalysis; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000737:chemistry; D007267:Injections; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D058105:Polymerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000464:Alginates; D002021:Buffers; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D005782:Gels; D000960:Hypolipidemic Agents; C519480:amorphous calcium phosphate; D019821:Simvastatin