Novel polymorphic form of adefovir dipivoxil derived from polymer-directed crystallization.
Crystallization is an essential step in pharmaceutical processing. The discovery of a non-classical crystallization pathway would be a promising strategy to engineer the properties of drug crystalline particles for specific delivery conditions. Herein, polymer-directed crystallization was successfully employed to modify the characteristics of a model drug, adefovir dipivoxil (AD). Polyacrylic acid (PAA), ethyl cellulose (EC), and hydroxypropyl cellulose were added as active polymers to control the crystallization pathway of AD. Changes in crystal habit were observed in all cases. A novel polymorph was found after the addition of PAA and EC, and was confirmed by XRD and DSC results. In FTIR investigations, the crystals derived from PAA-directed crystallization showed strong interactions between PAA and AD. The polymer content in polymer-directed crystallization-derived powders varied from 7 to 24 wt%, and the presence of polymers lead to sustained release of AD. These results make polymer-directed crystallization a simple and efficient technique to engineer the physical and chemical properties of drug crystals.
Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul, South Korea.
Min Kyung
MK
Lee
Hyeseung
H
Lee
Il Won
IW
Kim
Jonghwi
J
Lee
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D010316:Particle Size; D011108:Polymers; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D000998:Antiviral Agents; D063065:Organophosphonates; D011108:Polymers; D011208:Powders; D000225:Adenine; C106812:adefovir dipivoxil