Development and evaluation of injection-molded sustained-release tablets containing ethylcellulose and polyethylene oxide.
OBJECTIVE
It was the aim of the present study to develop sustained-release matrix tablets by means of injection molding of ethylcellulose (EC) and polyethylene oxide (PEO) mixtures and to evaluate the influence of process temperature, matrix composition, and viscosity grade of EC and PEO on processability and drug release.


METHODS
Formulations consisting of metoprolol tartrate (MPT, concentration: 30%), EC plasticized by dibutyl sebacate, and PEO were extruded and consequently injection molded into tablets. The influence of process temperature (120°C and 140°C), matrix composition, viscosity grade of EC (4, 10, 20, 45, and 100 mPa·s) and PEO (7 × 10(6), 1 × 10(6), and 1 × 10(5) Mw) on processability and drug release was determined.


RESULTS
Formulations consisting of 70% EC and 30% MPT showed incomplete drug release, whereas drug release was too fast for formulations without EC. Higher PEO concentrations increased drug release. Formulations containing 30% metoprolol, EC, and different concentrations of PEO showed first-order release rates with limited burst release. Drug release from direct compressed tablets showed faster drug release rates compared to injection-molded formulations. There was no clear relationship between the molecular weight of EC and drug release. The melting endotherm (113.9°C) of MPT observed in the differential scanning calorimeter thermogram of the tablets indicated that a solid dispersion was formed which was confirmed by X-ray diffractogram. X-ray tomography demonstrated a difference in pore structure between tablets processed at 120°C and 140°C.


CONCLUSIONS
It was concluded that injection molding can be applied successfully to develop sustained-release PEO/EC matrix tablets.
Quinten
T
T
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
De Beer
T
T
Almeida
A
A
Vlassenbroeck
J
J
Van Hoorebeke
L
L
Remon
J P
JP
Vervaet
C
C
D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D008790:Metoprolol / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D013607:Tablets; D013696:Temperature; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D044366:Transition Temperature; D014783:Viscosity; D014961:X-Ray Diffraction
D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D005079:Excipients; D013607:Tablets; D011092:Polyethylene Glycols; C055481:dibutyl sebacate; C013517:ethyl cellulose; D002482:Cellulose; D008790:Metoprolol