Drug-polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend.
Using spectroscopic and thermal analysis, this study investigated drug-polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL) (RL) and ethylcellulose (EC) binary blend (RL/EC = 2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from approximately 50 degrees C for the amorphous nifedipine to approximately 115 degrees C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend.
Huang
Jingjun
J
Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, 600 S 43rd Street, Philadelphia, PA 19104, USA. jingjun.huang@astrazeneca.com
Wigent
Rodney J
RJ
Schwartz
Joseph B
JB
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003460:Crystallization; D004355:Drug Stability; D006860:Hydrogen Bonding; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009543:Nifedipine / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D011108:Polymers; C058665:Eudragit RL; C013517:ethyl cellulose; D002482:Cellulose; D009543:Nifedipine