Investigations on the physical structure and the mechanism of drug release from an enteric matrix microspheres with a near-zero-order release kinetics using SEM and quantitative FTIR.
The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow size distributions with one size fraction comprising 70-80% of the yield. Scanning electron microscopy and quantitative Fourier transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism.
Obeidat
Wasfy M
WM
College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, UAE. wobeidat@sharjah.ac.ae
Obeidat
Safwan M
SM
Alzoubi
Nizar M
NM
D000180:Acrylic Resins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry*; D014783:Viscosity
D000180:Acrylic Resins; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C050528:Eudragit RS; D013806:Theophylline