APPLICATION OF FLOW-THROUGH DISSOLUTION METHOD FOR THE EVALUATION OF ORAL FORMULATIONS OF NIFEDIPINE

The drug release characteristics of three oral formulations (one conve ntional and 2 extended-retease) of nifedipine were evaluated using a f low-through apparatus. The experiments were conducted for 4 to 24 hour s using water or phosphate buffer (0.05 or 0.1 M; pH 7.4) with or with out solubilizing agent, Tween, as a dissolution medium at a flow rate of 12.5 mL/min. The drug concentrations were determined using an HPLC method based on ratios of peak heights corresponding to UV absorbances at 254 nm for nifedipine and nitrendipine (internal standard). Dissol ution characteristics in various media correspond to the nifedipine so lubility in the medium. Peak nifedipine concentrations with 0.05 M pho sphate buffer containing 0.5% Tween were significantly higher than tho se in the medium without Tween (21.5+/-1.0 vs 8.3+/-0.2 mu g/mL, p < 0 .001). Using a 0.05 M phosphate buffer with no Tween, the products tes ted showed distinct dissolution profiles representative of the respect ive formulation type. The conventional release product (10 mg) showed a higher mean peak nifedipine concentration (C-max,C-d) of 49.5+/-2.4 mu g/mL (p < 0.001) attained at (t(max,d)) 0.46+/-0.05 h as compared t o those of modified-release products. The corresponding mean values fo r the modified-release tablets were 8.3+/-0.2 and 2.6+/-0.3 mu g/mL fo r C-max,C-d, and 0.28+/-0.03 and 12.0+/-3.8 h for t(max,d) for the 20 and 30 mg tablets, respectively. Area under the concentration-time cur ves (AUC(0-t,d)) for the 10, 20 and 30 mg formulations were 12.3+/-0.4 , 20.5+/-2.6 and 32.6+/-3.7 mu g.h/mL, respectively (p < 0.001). As th e dissolution profiles are similar to those of plasma/serum drug conce ntrations-time profiles obtained from clinical studies, application of this dissolution method, along with the derived in vitro drug-release kinetics parameters for potential correlation with in vivo parameters are discussed. The results of this study show that, compared to the U SP dissolution method using apparatus 1 or 2, the flow-through dissolu tion system offers a potentially better alternative to assess drug rel ease characteristics for different types of formulations, especially f or drugs of low aqueous solubility such as nifedipine.