A COMPARATIVE BIOAVAILABILITY STUDY OF TWO TABLET FORMULATIONS OF DIPYRIDAMOLE
Abstract
New interest in dipyridamole has been stimulated by its role as a possible agent in the treatment of thromboembolic disease. The monitoring of plasma levels of this compound will most likely increase the need for rapid and specific assay methods. A high-performance liquid chromatography procedure has been developed to meet these needs. The procedure utilizes lidocaine as the internal standard and an ethyl acetate extraction from one milliliter of alkalinized plasma. Assay of the samples is accomplished by reversed-phase chromatography using a C(,18) column and a mobile phase consisting of a 50:50 mixture of acetonitrile and a 0.1 M aqueous solution of sodium phosphate adjusted to pH 7.0. Ultraviolet absorbance at a wavelength of 280 nm was used for the detection of the dipyridamole. Retention times of 5.6 and 7.5 minutes were obtained for dipyridamole and lidocaine. The sensitivity of the HPLC assay was less than 5 ng/ml of plasma. The peak height ratio of dipyridamole to lidocaine was a linear function of dipyridamole concentration over a range of 0.0 to 2,000 ng/ml of plasma. The mean percent recovery of dipyridamole from seven plasma samples was 96.83 (+OR-) 5.51. The analytical procedure was also very reliable with a percent coefficient of variation for the determination of dipyridamole in "spiked" plasma samples of only 2.69. Eleven test subjects participated in a randomized two-way crossover experiment in which each subject received two 25 mg tablets of two dipyridamole tablet formulations. From an analysis of the clinical study it was obvious that formulation A had both a faster rate of absorption and a greater clinical bioavailability when compared to formulation B. Formulation A was statistically different from formulation B with respect to t(,peak) and c(,peak) values. There appeared to be a direct correlation between the results of the in vivo clinical study and those of an in vitro dissolution study on the two formulations of dipyridamole. The mean t(,75%) values were 38.7 minutes and 220.0 minutes for formulations A and B, respectively. Formulation A had a faster rate of dissolution in the 0.1 N HCl medium which correlates well with the faster rate of absorption seen in the clinical study for the eleven subjects.
Degree
Ph.D.
Subject Area
Pharmaceuticals
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