title: Polymer-directed crystallization of atorvastatin.
abstract: Living organisms secrete minerals composed of peptides and proteins, resulting in "mesocrystals" of three-dimensional-assembled composite structures. Recently, this biomimetic polymer-directed crystallization technique has been widely applied to inorganic materials, although it has seldom been used with drugs. In this study, the technique was applied to the drowning-out crystallization of atorvastatin using various polymers. Nucleation and growth at optimized conditions successfully produced composite crystals with significant polymer contents and unusual characteristics. Atorvastatin composite crystals containing polyethylene glycol, polyacrylic acid, polyethylene imine, and chitosan showed a markedly decreased melting point and heat of fusion, improved stability, and sustained-release patterns. The use of hydroxypropyl cellulose yielded a unique combination of enhanced in vitro release and improved drug stability under a forced degradation condition. The formation hypothesis of unique mesocrystal structures was strongly supported by an X-ray diffraction pattern and substantial melting point reduction. This polymer-directed crystallization technique offers a novel and effective way, different from the solid dispersion approach, to engineer the release, stability, and processability of drug crystals.
authors.affiliation: Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Choi
authors.forename: Hyeseung
authors.initials: H
authors.lastname: Lee
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Jonghwi
authors.initials: J
authors.lastname: Lee
mesh_terms: D000924:Anticholesteremic Agents / Q000737:chemistry*; D000069059:Atorvastatin; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D006538:Heptanoic Acids / Q000737:chemistry*; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D033362:Powder Diffraction; D011758:Pyrroles / Q000737:chemistry*; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011108:Polymers; D011758:Pyrroles; D011092:Polyethylene Glycols; D002482:Cellulose; D048271:Chitosan; C008079:hydroxypropylcellulose; D000069059:Atorvastatin