DEVELOPMENT IN RELEASE TESTING OF TOPICAL DOSAGE FORMS - USE OF THE ENHANCER CELL(TM) WITH AUTOMATED SAMPLING

The aim of this study was to evaluate an automated method using the En hancer Cell(TM) and compare the release of the corticosteroid triamcin olone acetonide (TA) from commercial semisolid formulations. The metho d used a modified USP Apparatus 2 using the Enhancer Cell(TM) in 200 m l capacity flasks instead of the standard 900 ml flasks. The additiona l equipment included an adapter plate to position the flasks in the ce nter, a cover to reduce the receptor phase evaporation and smaller siz ed (1/4 in.) shaft and collets. All products were evaluated prior to t heir expiration date. Effects of system variables such as the temperat ure and composition of the receptor medium, stirring speed, and the ch oice of membrane on the drug release were evaluated. Statistical analy sis was carried out using SAS Ver. 6.07 and the slopes and intercepts (of the cumulative release/unit area versus square root of time plots) were compared. TA release was a linear function of the square root of time (P less than or equal to 0.0001), in accordance with Higuchi's m odel (r(2) greater than or equal to 0.9 in most cases). Temperature (3 2 and 37 degrees C) did not affect the drug release (P > 0.32) but a s ignificantly higher release rate was observed (P less than or equal to 0.0001) at 50 degrees C. Stirring speed (50, 100, 200 rpm) (P > 0.26) and receptor media composition (38 and 76% ethanol) (P > 0.68) did no t significantly alter the release rates. Membrane selection (regenerat ed cellulose, polyethylene, and rat skin) was found to be a significan t variable (P less than or equal to 0.004). This study demonstrates th e use of the Enhancer Cell(TM) as an automated quality control tool in the in vitro release testing procedure for semisolid drug formulation s. (C) 1998 Elsevier Science B.V. All rights reserved.