Development and bioequivalence study of potassium chloride extended release tablets

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Extended-release potassium chloride formulations are crucial for managing hypokalemia.
• Ensuring bioequivalence of generic drug products is essential for therapeutic substitution and cost-effectiveness.

Purpose of the Study:

• To develop a generic extended-release tablet of potassium chloride (PC) 600 mg.
• To compare the potassium absorption of the developed generic tablet with Kaleorid® LP 600 mg.

Main Methods:

• Matrix core tablets were prepared using carnauba wax as a retardant.
• Core tablets were coated with ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) blends to control drug release.
• A two-treatment, two-period, two-sequence crossover bioequivalence study was conducted in 24 healthy volunteers.
• Potassium ion absorption was assessed by measuring urinary excretion using a selective electrode.

Main Results:

• An optimized coating blend (41.75% EC, 58.25% HPMC) with 4.5% weight gain yielded dissolution profiles similar to Kaleorid®.
• Bioequivalence analysis showed that the test product's cumulative urinary potassium excretion (Ln Ae0-24) and maximal excretion rate (Rmax) fell within the 80%-125% bioequivalence interval of the reference product.
• The 90% confidence intervals for the test product were 99.08%-100.92% for cumulative excretion and 97.34%-102.66% for maximal excretion rate.

Conclusions:

• The developed generic extended-release potassium chloride 600 mg tablet is bioequivalent to Kaleorid® LP 600 mg.
• The formulation utilizing carnauba wax and EC/HPMC coating effectively modulates potassium release for comparable absorption.
• This generic formulation offers a therapeutically equivalent alternative to the reference product.