Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.
The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.
Young
Christopher R
CR
Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. cryoung76@rcn.com
Dietzsch
Caroline
C
Cerea
Matteo
M
Farrell
Thomas
T
Fegely
Kurt A
KA
Rajabi-Siahboomi
Ali
A
McGinity
James W
JW
D000179:Acrylates; D000465:Algorithms; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004355:Drug Stability; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry*; D013818:Thermogravimetry
D000179:Acrylates; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D005079:Excipients; D011109:Polymethacrylic Acids; D011208:Powders; C117167:carbopol 974P NF; C030613:polymethacrylic acid; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D013806:Theophylline