Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion.
The objective of this research project was to determine the physicochemical properties and investigate the drug release mechanism from ethyl cellulose (EC) matrix tablets prepared by either direct compression or hot-melt extrusion (HME) of binary mixtures of water soluble drug (guaifenesin) and the polymer. Ethyl cellulose was separated into "fine" or "coarse" particle size fractions corresponding to 325-80 and 80-30 mesh particles, respectively. Tablets containing 30% guaifenesin were prepared at 10, 30, or 50 kN compaction forces and extruded at processing temperatures of 80-90 and 90-110 degrees C. The drug dissolution and release kinetics were determined and the tablet pore characteristics, tortuosity, thermal properties and surface morphologies were studied using helium pycnometry, mercury porosimetry, differential scanning calorimetry and scanning electron microscopy. The tortuosity was measured directly by a novel technique that allows for the calculation of diffusion coefficients in three experiments. The Higuchi diffusion model, Percolation Theory and Polymer Free Volume Theory were applied to the dissolution data to explain the release properties of drug from the matrix systems. The release rate was shown to be dependent on the ethyl cellulose particle size, compaction force and extrusion temperature.
Crowley
Michael M
MM
Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. mmcrowley@mail.utexas.edu
Schroeder
Britta
B
Fredersdorf
Anke
A
Obara
Sakae
S
Talarico
Mark
M
Kucera
Shawn
S
McGinity
James W
JW
D002482:Cellulose / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D005100:Expectorants; D006140:Guaifenesin; D007700:Kinetics; D010316:Particle Size; D012597:Sclerosing Solutions; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
D003692:Delayed-Action Preparations; D005100:Expectorants; D012597:Sclerosing Solutions; D013607:Tablets; D006140:Guaifenesin; C013517:ethyl cellulose; D002482:Cellulose