摘要
The purposes of this study are to prepare the generic extended release tablet of potassiumchloride(PC) 600 mg and to compare the absorption of potassium ion from the experimen-tal tablets to that of Kaleorid? LP 600 mg(Leo Pharmaceutical Products, Denmark). Car-nauba wax was used as retardant in the matrix core tablets. The core tablets were coatedwith blends of ethyl cellulose(EC) and hydroxypropyl methyl cellulose(HPMC) to modulatethe drug release. Results of a selective two-level, three-factor experiment design revealedthat a blend of 41.75% of EC and 58.25% of HPMC at 4.5% weight gained could produce thecoated tablets having dissolution profiles similar to those of Kaleorid?. A two-treatment,two-period, two-sequence crossover bioequivalence study was carried out on 24 healthyvolunteers to compare the absorption of potassium ion from experimental tablets to thatfrom Kaleorid?. The potassium ion in the urine was measured by a selective electrode of theADVIA 1650 system(Bayer) and used to calculate cumulative urinary excretion and urinaryexcretion rate. Results of 90 percent confidence interval analysis showed that the limits fornatural log-transformed cumulative urinary potassium excretion(Ln Ae 0-24) of test productwere in the range of 3.73–3.79 mEq, corresponding to 99.08%–100.92% of Kaleorid ?, respec-tively, and the limits for natural log-transformed maximal potassium excretion rate( R max) oftest product were in the range of 1.72–1.82 mEq/h, corresponding to 97.34%–102.66% of refer-ence product, respectively. Both of them fell within the bioequivalence interval(80%–125%)of reference product, proving that experimental product is bioequivalent to Kaleorid ?.
The purposes of this study are to prepare the generic extended release tablet of potassiumchloride(PC) 600 mg and to compare the absorption of potassium ion from the experimen-tal tablets to that of Kaleorid? LP 600 mg(Leo Pharmaceutical Products, Denmark). Car-nauba wax was used as retardant in the matrix core tablets. The core tablets were coatedwith blends of ethyl cellulose(EC) and hydroxypropyl methyl cellulose(HPMC) to modulatethe drug release. Results of a selective two-level, three-factor experiment design revealedthat a blend of 41.75% of EC and 58.25% of HPMC at 4.5% weight gained could produce thecoated tablets having dissolution profiles similar to those of Kaleorid?. A two-treatment,two-period, two-sequence crossover bioequivalence study was carried out on 24 healthyvolunteers to compare the absorption of potassium ion from experimental tablets to thatfrom Kaleorid?. The potassium ion in the urine was measured by a selective electrode of theADVIA 1650 system(Bayer) and used to calculate cumulative urinary excretion and urinaryexcretion rate. Results of 90 percent confidence interval analysis showed that the limits fornatural log-transformed cumulative urinary potassium excretion(Ln Ae 0-24) of test productwere in the range of 3.73–3.79 mEq, corresponding to 99.08%–100.92% of Kaleorid ?, respec-tively, and the limits for natural log-transformed maximal potassium excretion rate( R max) oftest product were in the range of 1.72–1.82 mEq/h, corresponding to 97.34%–102.66% of refer-ence product, respectively. Both of them fell within the bioequivalence interval(80%–125%)of reference product, proving that experimental product is bioequivalent to Kaleorid ?.
基金
Financial support for bioequivalence study from The Department of Science and Technology (grant number 209/HDSKHCN) of Ho chi Minh city (DOST)
