pH-Sensitive polymer blends used as coating materials to control drug release from spherical beads: elucidation of the underlying mass transport mechanisms.
OBJECTIVE
To elucidate the drug release mechanisms from pellets coated with pH-sensitive polymer blends.


METHODS
Verapamil hydrochloride-loaded beads were coated with various blends of a water-insoluble and an enteric polymer, ethylcellulose:Eudragit L and Eudragit NE:Eudragit L, respectively. Both experimental and theoretical techniques were used to characterize the systems before and upon exposure to 0.1 M HCl and phosphate buffer (pH 7.4).


RESULTS
Using analytical solutions of Fick's second law of diffusion, optical and scanning electron microscopy, and mechanical and gravimetric analysis, new insight into the underlying drug release mechanisms could be gained. More importantly, the latter can be effectively altered by varying the type of polymer blend and blend ratio. For example, at low pH drug release is primarily controlled by diffusion through the intact film coatings in Eudragit NE:Eudragit L blends, whereas crack formation is of major importance in ethylcellulose:Eudragit L-coated systems. At high pH, the (partial) leaching of the enteric polymer out of the coatings plays an important role. In all cases, the observed drug release profiles could be explained based on the occurring mass transport processes.


CONCLUSIONS
The obtained new knowledge can be used to effectively adjust desired drug release mechanisms and, thus, release patterns.
Lecomte
Florence
F
College of Pharmacy, Freie Universitaet Berlin, Kelchstrasse 31, 12169, Berlin, Germany.
Siepmann
Juergen
J
Walther
Mathias
M
MacRae
Ross J
RJ
Bodmeier
Roland
R
D000180:Acrylic Resins / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry; D014867:Water / Q000032:analysis / Q000737:chemistry
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; C477853:Eudragit NE 30-D; D008689:Methacrylates; D011108:Polymers; D014867:Water; C013517:ethyl cellulose; D002482:Cellulose; D014700:Verapamil