Mar 3, 2008 - layer thickness happ for a BCS II model drug, fenofibrate, in a USP dissolution apparatus II; and. (2) illustrate the dependence of happ on ...
Particle Diffusional Layer Thickness in a USP Dissolution Apparatus II: A Combined Function of Particle Size and Paddle Speed JENNIFER J. SHENG,1 PAUL J. SIROIS,2 JENNIFER B. DRESSMAN,3 GORDON L. AMIDON1 1
College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109-1065
2
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285
3
Institute for Pharmaceutical Technology, Biocenter-Johann Wolfgang Goethe-University, Frankfurt 60439, Germany
Received 2 August 2007; revised 25 December 2007; accepted 27 December 2007 Published online 3 March 2008 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.21345
ABSTRACT: This work was to investigate the effects of particle size and paddle speed on the particle diffuisonal layer thickness happ in a USP dissolution apparatus II. After the determination of the powder dissolution rates of five size fractions of fenofibrate, including 99% purity), sodium lauryl sulfate and all other chemicals were of analytical grade and were purchased from Sigma Chemical Company (St. Louis, MO). Distilled, deionized and filtered water was prepared in house and used for all experiments. Fenofibrate ‘‘as received’’ from Sigma had a broad size distribution, with which four size fractions, that is, 20–32, 32–45, 63–75, and 90–106 mm were obtained by sieving. In brief, the bulk material was initially dry sieved through the USA standard test sieves (Newark Wire Cloth Company, Clifton, NJ). Then, 300 mg of the dry sieved fractions were well suspended into 60 mL of 0.9% NaCl solution containing 0.05% SLS, and the suspensions were wet sieved through the same standard sieves. The wet sieved fractions on the sieve were rinsed with 0.9% NaCl solution containing 0.05% SLS and subsequently with water, and then they were dried overnight in a vacuum oven at 308C. The 90–106 mm size fractions. This observation is consistent with the larger surface area per unit weight of the smaller particles. Secondly, the dissolution rates of the jet-milled material are similar at the 50 and 100 rpm. Finally, the four larger size fractions of fenofibrate dissolve faster at a paddle speed of 100 rpm than at 50 rpm, presumably due to the higher fluid velocities at 100 rpm that lead to
thinning of happ and subsequently more efficient mass transfer.
Dependence of Diffusional Layer Thickness on Hydrodynamics and Particle Sizes The dependence of happ on particle size and hydrodynamics/fluid velocity were examined and illustrated in the two following ways. The first approach is bifunctional analysis demonstrating happ as a function of r under different paddle speeds, as shown in Figure 6. This approach determined the transitional particle size through which the value of happ exhibits a
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 97, NO. 11, NOVEMBER 2008
DOI 10.1002/jps
PARTICLE DIFFUSIONAL LAYER THICKNESS IN USP DISSOLUTION APPARATUS II
Figure 2. Overlay of powder X-ray diffraction patterns of jet-milled fenofibrate particles of
