Development and bioequivalence study of potassium chloride extended release tablets

Abstract

The purposes of this study are to prepare the generic extended release tablet of potassium chloride (PC) 600 mg and to compare the absorption of potassium ion from the experimental tablets to that of Kaleorid® LP 600 mg (Leo Pharmaceutical Products, Denmark). Carnauba wax was used as retardant in the matrix core tablets. The core tablets were coated with blends of ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) to modulate the drug release. Results of a selective two-level, three-factor experiment design revealed that a blend of 41.75% of EC and 58.25% of HPMC at 4.5% weight gained could produce the coated tablets having dissolution profiles similar to those of Kaleorid®. A two-treatment, two-period, two-sequence crossover bioequivalence study was carried out on 24 healthy volunteers to compare the absorption of potassium ion from experimental tablets to that from Kaleorid®. The potassium ion in the urine was measured by a selective electrode of the ADVIA 1650 system (Bayer) and used to calculate cumulative urinary excretion and urinary excretion rate. Results of 90 percent confidence interval analysis showed that the limits for natural log-transformed cumulative urinary potassium excretion (Ln Ae0-24) of test product were in the range of 3.73–3.79 mEq, corresponding to 99.08%–100.92% of Kaleorid®, respectively, and the limits for natural log-transformed maximal potassium excretion rate (Rmax) of test product were in the range of 1.72–1.82 mEq/h, corresponding to 97.34%–102.66% of reference product, respectively. Both of them fell within the bioequivalence interval (80%–125%) of reference product, proving that experimental product is bioequivalent to Kaleorid®. Keywords: Potassium chloride, Ethyl cellulose, Hydroxypropyl methyl cellulose, Extended release tablet, Cumulative urinary excretion, Urinary excretion rate