Prediction of in vivo drug release behavior of controlled-release multiple-unit dosage forms in dogs using a flow-through type dissolution test method

In vitro methods to assess drug precipitation

“…Compared with USP I/II dissolution methods, FTC methods have the advantage of allowing a change in the dissolution medium during each run, which allows for better simulation of the pH gradient and fluids associated with transit throughout the gastrointestinal tract (Thoma and Ziegler, 1998). Also, they simulate in vivo hydrodynamics more closely than the USP I/II dissolution methods (Perng et al, 2003;Qureshi et al, 1994), and demonstrate good in vitro/in vivo correlations (Derendorf et al, 1983;Ikegami et al, 2003;Qureshi et al, 1994;Sunesen et al, 2005). Another advantage is that FTC methods at low flow rates are more sensitive to detect differences in the disintegration properties than other USP dissolution methods (Wennergren et al, 1989).…”

Bioavailability and in Vivo Release Behavior of Controlled-Release Multiple-Unit Theophylline Dosage Forms in Beagle Dogs, Cynomolgus Monkeys, and Göttingen Minipigs

“…After drying, the beads were sieved (no. 22 sieve, <0.7 mm) to remove both the agglomerate and the fine particles 14…”

“…The operating conditions of the coating process were as follows: spray solution feed, 6 mL/min; spray air pressure, 1 kg/cm 2 ; blower rate, 100–200 L/min; blower temperature, 50°C; and rotating speed, 150 rpm. The film‐coated beads were oven‐dried for 16 h at 45°C 14. The formula of EC‐coated beads of TP is listed in Table 1.…”

“…The dogs were fasted for 20 h prior and for 10 h after the drug administration, but they were allowed free access to water. Blood samples were withdrawn at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 27, and 30 h after administration and plasma samples were stored frozen until assay and TP in plasma was measured by previously reported HPLC method 13,14…”

“…For this purpose, porous ethylcellulose (EC)‐coated bead formulations containing theophylline (TP), used as the model drug and which can be absorbed from entire intestine,12 were orally administered to four dogs, three monkeys, and three minipigs, and the bioavailability parameters in the three species were compared. EC‐coated beads with time to 50% TP release shown about 7 h were used for this study, because the relative bioavailability of this formulation in dogs were not sufficient 13,14. In addition, the in vivo TP release from EC‐coated beads in dogs, monkeys, and minipigs measured to evaluate the relationship between the in vivo release and their bioavailability.…”