Journal
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
Volume 39, Issue 7, Pages 1070-1083Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2012.702350
Keywords
Hot melt extrusion (HME); controlled release (CR); hydroxypropyl methylcellulose (methocel, HPMC); theophylline; propylene glycol (PG); crystalline
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The objective of this study was to develop hydroxypropyl methylcellulose (HPMC) based controlled release (CR) formulations via hot melt extrusion (HME) with a highly soluble crystalline active pharmaceutical ingredient (API) embedded in the polymer phase. HPMC is considered a challenging CR polymer for extrusion due to its high glass transition temperature (T-g), low degradation temperature, and high viscosity. These problems were partially overcome by plasticizing the HPMC with up to 40% propylene glycol (PG). Theophylline was selected as the model API. By using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and X-ray powder diffraction (XRPD), the physical properties of the formulations were systematically characterized. Five grades of HPMC (Methocel (R)) - E6, K100LV, K4M, K15M, and K100M - were tested. The extrusion trials were conducted on a 16 mm twin screw extruder with HPMC/PG placebo and formulations containing theophylline/HPMC/PG (30:42:28, w/w/w). The dissolution results showed sustained release profiles without burst release for the HPMC K4M, K15M, and K100M formulations. The extrudates have good dissolution stability after being stressed for 2 weeks under 40 degrees C/75% RH open dish conditions and the crystalline API form did not change upon storage. Overall, the processing windows were established for the HPMC based HME-CR formulations.
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